1

Topic proposal

I understand that this proposal will be retained by the SIGN Programme Lead and be made available on the SIGN website for time period that the proposal is being considered. Only proposals with a completed Declaration of Interests for the principal proposer will be considered

1. What is the problem/need for a guideline/clinical scenario?

Prevention and early recognition and treatment of type 2 diabetes

2. Burden of the condition

The Scottish Diabetes Survey (2016), shows that 257,728 have type 2 diabetes. This is around 88% of all diabetes cases in Scotland.

There are around 17,000 new cases each year, and Diabetes UK estimates that over 500,000 people in Scotland are at risk of developing type 2 diabetes.

There is a strong correlation between obesity, type 2 diabetes and other chronic health conditions.

87% of people in Scotland with type 2 diabetes are overweight or obese.

65% of adults in Scotland are overweight including 29% who were obese (Scottish Health Survey: 2016).

Obese people are 7 times more likely to develop type 2 diabetes than those with a healthy weight; overweight people are 3 times more likely.

People in social class 5 (unskilled manual) are three and a half times more likely to be ill as a result of the complications of diabetes than those in social class 1 (professional). Moreover, short term mortality risk from type 2 diabetes is higher among those living in more deprived areas. All these factors are inextricably linked to the risk of diabetes or the risk of serious complications for those already diagnosed.

The economic costs to Scotland of type 2 diabetes, which is closely associated with overweight and obesity, is estimated at £2.37bn per annum, taking into account loss of productivity due to impaired health, direct health care costs and investment to mitigate the impact of obesity.

The cost to the Health Service of treating type 2 diabetes alone is estimated at £800m – around 9% of total health expenditure.

3. Variations

Current provision of weight management services for the prevention and treatment of type 2 diabetes differs significantly across NHS boards. This includes variations in the type of programmes that are offered, duration and follow up, health care professionals involved in delivery, eligibility and access criteria for these services and where and how the services are delivered. There is also differences in recording data related to the weight management services. These issues are evidenced in Read, S., and Logue, J. (2016) Variations in weight management services in Scotland: a national survey of weight management provision. Journal of Public Health, 38(3), e325-e335. (doi:10.1093/pubmed/fdv132).

4. Areas of uncertainty to be covered

Key question 1 How can we identify those at increased risk of developing type 2 diabetes?

Key question 2 What interventions, such a lifestyle, diet, physical activity and pharmacological therapy, have been shown to prevent progression to type 2 diabetes in individuals at increased risk?

Key question 3 What non-pharmacological intervention such as lifestyle, diet, physical acitivity, bariatric surgery have been successful in achieving remission of type 2 diabetes?

2

Key question 4 [What training/ education provides the best support for health and social care professionals to have conversations around weight and risks of developing type 2 diabetes?]

5. Areas that will not be covered

The guideline will focus on the prevention, early detection and early non-pharmacological treatment of type 2 diabetes. Therefore areas that will not be covered would include issues relating to the pharmacological treatment of type 2 diabetes (covered in SIGN 154) and issues related to type 1 diabetes.

6. Aspects of the proposed clinical topic that are key areas of concern for patients, carers and/or the organisations that represent them

Key concerns amongst individuals ‘at risk’ of or with type 2 diabetes are the development of progressive microvascular and macrovascular complications. These include blindness, renal failure and amputation as well as premature cardiovascular disease and ultimately life loss. Enabling those at increased risk of developing type 2 diabetes to access services which will support them in delaying or avoiding onset of the condition is key to providing individuals care which is person-centred. This is in keeping with aspirations that the NHS delivers services focused on ‘what matters to you’. Raising awareness of factors which increase risks of developing type 2 diabetes requires there to be equitable provisions of effective tools and services which will enable individuals to assess their risk and access interventions which are best suited to them.

7. Population

Included

Those at risk of developing type 2 diabetes due to age, ethnicity, weight and family history.

Those clinically diagnosed with prediabetes, impaired glucose tolerance, impaired fasting hyperglycaemia or previous gestational diabetes

Those recently diagnosed with type 2 diabetes (within 6 years)

Not included The not at-risk general population.

8. Healthcare setting

Services for the prevention of diabetes take place in both NHS Scotland settings – through weight management services, primary care, psychology and diabetes specialist clinics – and also in the community through delivering services where appropriate at local leisure centres, community centres, schools, workplaces and faith centres.

9. Potential

Potential to improve current practice across Scotland An up to date guideline detailing evidence based interventions to prevent type 2 diabetes has the potential to improve and standardise the approach to identifying people at risk of type 2 diabetes and ensure that programmes targeting type 2 diabetes prevention are more likely to be effective. There is also the potential to ensure more equitable access to services for at-risk individuals and a standardised approach to interventions for those found to have type 2 diabetes. Up to date guidance will allow care providers to have a clear approach to what services should be delivered and that resource is directed towards a service that have been shown to prevent type 2 diabetes as well as supporting person centred care models.

Potential impact on important health outcomes Utilising the existing evidence base to provide guidance on best practice will help support national initiatives to prevent type 2 diabetes. If in Scotland we can delay or avoid onset of type 2 diabetes at a national level then this is likely to impact in the short term to improved

3

identification of those at risk or those with undiagnosed type 2 diabetes and therefore direct patients to an appropriate intervention. Furthermore, in the medium to long term sustained weight loss will improved glycaemic control, and reduce risks associated with complications such as cardiovascular disease, renal disease, sight loss and foot complications. This in turn will see a reduction in the prevalence of type 2 diabetes and see more people with type 2 diabetes achieve remission. Diabetes is in a fortunate position whereby we have a SCI-diabetes, a national IT system, that collects all the information around demographics, treatments, interventions and outcomes of all individuals with diabetes. We can therefore evaluate a number of health outcomes including progression rates of those with prediabetes to type 2 diabetes and similarly look at trends between gestational diabetes and type 2 diabetes.

Potential impact on resources Up to date guidance will encourage that resources are used in an evidence based manner. This will maximise the impact that these resources have on improving the outcome for the individual as well as healthcare utilisation at a local, regional and national level. Through SCI Diabetes, as detailed above, it would be possible to review pathways to consider uptake rates and completion rates of programmes as well as look at mean and sustained weight loss as a result of these interventions. In the longer term it will also be possible to consider any reduction on the prescription of diabetes medications and provision of weight management interventions.

10. What evidence based guidance is currently available?

Out-of-date (list)

Current (list) NICE (2018) National Strategy and policy to prevent type 2 diabetes SIGN 116: Management of diabetes SIGN 154: Pharmacological management of glycaemic control in people with type 2 diabetes

11. Relevance to current Scottish Government policies

The framework for the prevention, early detection and early intervention of type 2 diabetes was published in July 2018. The framework provide national guidance on weight management interventions for those identified as ‘at risk’ of developing type 2 diabetes as well as those recently diagnosed. It aims to address the inconsistency of access and availability of weight management services across Scotland and highlight the need for integrated health and social care services. The framework includes:

Action to be taken at a national level around addressing stigma and awareness raising

A consistent approach of risk assessment for the early identification of populations ‘at risk’.

Guidance on how to provide a comprehensive weight management service including integration with diabetes specialist, physical activity, psychology, maternal health and education.

Provision of evidenced-based weight management interventions related to the level of risk for an individual – including specific programmes for those with prediabetes, gestational diabetes and targeted weight management for remission.

Encourages action to be taken to reduce health inequalities and emphasises the value of coproduction.

The framework supports work to Priority One of the Diabetes Improvement Plan (2014) – we aim to establish and implement approaches to support the prevention and early detection of type 2 diabetes, and to implement measures to promptly detect and prevent the complications of diabetes.

4

It also forms part of the action of Outcome 3 of the Diet and Healthy Weight Delivery Plan – people have access to effective weight management services. £42m has been invested for the implementation of this framework and five early adopter sites will begin implementation through a quality improvement methodology in Summer 2018. This will inform learning ahead of a national adoption in 2019/20.

12. Who is this guidance for?

All disciplines who could play an active role in the prevention of diabetes including those working in primary care, weight management, psychology, maternal health and diabetes specialist clinics. This would also help support NHS health boards, Integrated Joint Boards, Local authorities and Community Planning Partnerships in taking an evidence based approach to preventing type 2 diabetes where wider work in the community setting and through regulation is supported by comprehensive weight management service.

13. Implementation

Links with existing audit programmes The clinical priorities team Scottish Government and the Scottish Diabetes Group currently oversees the Diabetes Quarterly Reporting Process for Health Boards and Diabetes MCNs across Scotland. This process assesses performance against 12 key measures including assessment of glycaemic control in type 2 diabetes as well as complication rates and disease outcomes. There is ongoing revision of this work stream to ensure they incorporate measures relevant to the type 2 diabetes prevention framework. The type 2 diabetes prevention subgroup of the Scottish Diabetes Group are working on this at present and further information on potential measures are detailed below.

Existing educational initiatives As detailed above, there is currently extensive work in defining and implementing the framework for the prevention, early detection and early intervention of type 2 diabetes. This therefore provides an excellent opportunity for updated SIGN guidance to be disseminated throughout the diabetes community and ensure adoption at local, regional and national level. Strategies for monitoring implementation This will be key to determining the success of the guideline and also the framework for the prevention, early detection and early intervention of type 2 diabetes. Fortunately there are several processes in place that will aid in monitoring implementation of the guideline. Data from SCI-diabetes allows detailed reporting of several different indicators. Information from SCI-diabetes informs the existing diabetes quarterly reporting process as well as the annual Scottish Diabetes Survey. The type 2 diabetes prevention subgroup of the Scottish Diabetes Group are currently defining the measures relevant to the type 2 diabetes prevention framework. These will be incorporated into the health board diabetes quarterly reporting and are likely to include such measures as the rate of progression from prediabetes to type 2 diabetes, the rate of prediabetes, disease burden (i.e. retinopathy) at the diagnosis of type 2 diabetes. We will also look to assess remission rates for type 2 diabetes. The longitudinal nature of this data can assist in monitoring the impact that implementation SIGN guidance may have on these parameters. We are looking to ensure that the reporting system allows us to monitor this at national, health board and individual unit/GP/cluster level. This can be used to identify regional variation which in turns allows examination of care processes which helps inform health improvement initiatives at local regional and national level.

14. Primary contact for topic proposal

Brian Kennon

15. Group(s) or institution(s) supporting the proposal

Scottish Diabetes Group

5

Declaration of Interests Please complete all sections and if you have nothing to declare please put ‘N/A

Having read the SIGN Policy on Declaration of Competing Interests I declare the following competing interests for the previous year, and the following year. I understand that this declaration will be retained by the SIGN Programme Lead and be made available on the SIGN website for time period that the proposal is being considered.

Signature:

Name: Brian Kennon

Relationship to SIGN: Topic proposal primary contact

Date:

Date received at SIGN:

Personal Interests Remuneration from employment

Name of Employer and Post held

Nature of Business Self or partner/ relative

Specific?

Details of employment held which may be significant to, or relevant to, or bear upon the work of SIGN

Remuneration from self employment

Name of Business Nature of Business Self or partner/ relative

Specific?

Details of self employment held which may be significant to, or relevant to, or bear upon the work of SIGN

Remuneration as holder of paid office Nature of Office

held Organisation

Self or partner/

relative

Specific?

Details of office held which may be significant to, or relevant to, or bear upon the work of SIGN

6

Remuneration as a director of an undertaking Name of

Undertaking

Nature of Business

Self or partner/ relative

Specific?

Details of directorship held which may be significant to, or relevant to, or bear upon the work of SIGN

Remuneration as a partner in a firm

Name of Partnership

Nature of Business

Self or partner/ relative

Specific?

Details of Partnership held which may be significant to, or relevant to, or bear upon the work of SIGN

Shares and securities Description of

organisation Description of

nature of holding (value need not be

disclosed)

Self or partner/ relative

Specific?

Details of interests in shares and securities in commercial healthcare companies, organisations and undertakings

Remuneration from consultancy or other fee paid work commissioned by, or gifts from, commercial healthcare companies, organisations and undertakings

Nature of work For whom undertaken and

frequency

Self or partner/ relative

Specific?

Details of consultancy or other fee paid work which may be significant of to, or relevant to, or bear upon the work of SIGN

7

Details of gifts which may be significant to, or relevant to, or bear upon the work of SIGN

Non-financial interests Description of interest Self or partner/ relative

Specific?

Details of non-financial interests which may be significant to, or relevant to, or bear upon the work of SIGN

Non-personal interests Name of company, organisation or

undertaking

Nature of interest

Details of non- personal support from commercial healthcare companies, organisations or undertakings

Signature Date:

Thank you for completing this form.

Please return to Roberta James SIGN Programme Lead SIGN Executive, Healthcare Improvement Scotland, Gyle Square | 1 South Gyle Crescent | Edinburgh | EH12 9EB t: 0131 623 4735 e:roberta.james@nhs.net

Data Protection

Your details will be stored on a database for the purposes of managing this guideline topic proposal. We may retain your details so

that we can contact you about future Healthcare Improvement Scotland activities. We will not pass these details on to any third

parties. Please indicate if you do not want your details to be stored after the proposal is published.

8

Initial screen

Purpose: initial screening by SIGN Senior Management Team to exclude proposals that are neither

clinical, nor multi-professional, nor appropriate for the SIGN process.

1. Is this an appropriate clinical topic for a SIGN guideline? Is it a clinical topic, what is the breadth of the topic and is there a need for the guideline as identified in the proposal?

Yes, this is a clinical topic and addressed an important issue in NHSScotland. There is a need for the guideline as communicated by the Scottish Diabetes Group.

2. Is there a suitable alternative product which would address this topic? Would another Healthcare Improvement Scotland product better address the topic?

No

3. Has this topic been considered before and rejected? What were the reasons for rejection and are they still applicable

No

4. Outcome

Go forward to the next stage of topic selection

YES 19/10/2018

Reject

9

Scope of recent evidence

Summary: Only type 2 diabetes was covered, however, if the interventions desired are actually to prevent obesity and

indirectly to prevent diabetes then this will result in many more search results and will need to be

considered if they are in the scope of the guideline.

Ongoing research in the UK and Scotland was identified via Diabetes UK. There were seven highly relevant

projects which will likely be of great interest in the future, but are as yet unpublished.

Guidelines There are a number of existing UK/Scottish guidelines or frameworks on this topic in the public health

arena (publishes 2011–2018). Internationally there were two (CDC and ADA) from the USA, both from

2018. The topics covered included: identifying those at high risk of diabetes, monitoring for the

development of diabetes in those with prediabetes, lifestyle-change programmes (physical activity, eight

management and dietary advice) and population and community-level interventions.

Health technology assessments There were no HTAs. Cochrane reviews There were nine Cochrane reviews ranging from 2005 to 2017. The interventions included methods to identify those at risk of type 2 diabetes, diet, physical activity, weight loss (including pharmacological) in those at risk of or with type 2 diabetes. A further 50 systematic reviews and over 3,000 (unsifted results) randomised controlled trials were identified. See Annex 1 for further details

10

Suitability screen

Purpose: screening by the Guideline Programme Advisory Board to select applications suitable for inclusion

in the SIGN topic selection process.

1. Is there an owner for the project? (preferably an individual)

Yes

2. Is this a clinical priority area for NHSScotland?

The cost to the NHS managing people with type 2 and associated complications is great, and has a wider impact due to impaired health. Scottish Government published a framework for the prevention, early detection and early intervention of type 2 diabetes was published in July 2018, with funding for implementation.

3. Is there a gap between current and optimal practice? OR Is there wide variation in current practice? (is this an area of clinical uncertainty)

There are variations in the type of weight management programmes that are offered and how they are delivered.

4. Is there a suitable guideline already available that could be adapted? (not necessarily by SIGN)

Guidelines from NICE are available.

5. Is there adequate literature to make an evidence-based decision about appropriate practice? (is effective intervention proven and would it reduce mortality or morbidity)

There is a body of literature on which to base recommendations.

6. Would the proposed practice change result in sufficient change in outcomes (health status, provider and consumer satisfaction and cost) to justify the effort?

There is a potential to change practice by standardising the approach to identifying people at risk and offering effective interventions. Preventing or delaying onset of type 2 diabetes will have an impact on individuals’ health and quality of life, and in the long term reduce morbidity from complications.

How big is the gap?

Not clear, although data is available from SCI-diabetes, a national IT system that collects all the information around demographics, treatments, interventions and outcomes of all individuals with diabetes.

How much effort will it take to close the gap?

Not clear.

7. Is there a perceived need for the guideline, as indicated by a network of relevant stakeholders?

There is a need as communicated by the Scottish Diabetes Group.

8. Is there a reasonable likelihood that NHSScotland could implement the change?

There is currently work underway to defining and implement the framework for the prevention, early detection and early intervention of type 2 diabetes, which, in conjunction with the Scottish Diabetes Group will ensure dissemination throughout the diabetes community and

11

adoption at local, regional and national level. Implementation will be monitored through SCI-diabetes and the annual Scottish Diabetes Survey.

9. Does the proposer have any conflicts of interest? If so how will these be managed?

No

10. Outcome

Go forward to the next stage of topic selection

YES 30/01/2019

Reject

11. Decision

Ratified by SIGN Council for inclusion on the SIGN guideline development programme

Date 13/02/2019

Comment

12

Annex 1 Scope of recent evidence

Resources searched: Guidelines

NICE – 2 Scottish Government – 2 Public Health England – 2 NHS England – 1 CDC – 1 GIN – Nothing additional NGC – No longer available TRIP Database – Nothing additional Systematic Reviews and HTAs - English only

Cochrane (2005-2018) - 9 DARE – Not updated since 2014 UKHTA – Not updated since 2014 NIHR - 0 EUNetHTA- 0 Medline (2013-2018) - 48 Embase (2013-2018) – 2 RCTS – 2013 -2018, English only, RCT filters Numbers only

CENTRAL 3415 Medline 270 Embase 346

Guidelines

American Diabetes Association (2018). Prevention or Delay of Type 2 Diabetes: Standards of Medical Care in Diabetes 2018. c At least annual monitoring for the development of diabetes in those with prediabetesis suggested. E c Patients with prediabetes should be referred to an intensive behavioral lifestyleintervention program modeled on the Diabetes Prevention Program to achieveand maintain 7% loss of initial body weight and increase moderate-intensityphysical activity (such as brisk walking) to at least 150 min/week. A c Technology-assisted tools including Internet-based social networks, distancelearning, and mobile applications that incorporate bidirectional communicationmay be useful elements of effective lifestyle modification to preventdiabetes. B c Given the cost-effectiveness of diabetes prevention, such intervention programsshould be covered by third-party payers. B CDC (2018). National Diabetes Prevention Program - USA. https://www.cdc.gov/diabetes/prevention/index.html NHS England (2018). NHS Diabetes Prevention Programme (NHS DPP). Most people would be shocked to know that around 22,000 people with diabetes die early every year. Type 2 diabetes is a leading cause of preventable sight loss in people of working age and is a major contributor to kidney failure, heart attack, and stroke. There are currently 3.4 million people with Type 2 diabetes in England with around 200,000 new diagnoses every year. While Type 1 diabetes cannot be prevented and is not linked to lifestyle, Type 2 diabetes is largely preventable through lifestyle changes. One in six of all people in hospital have diabetes – while diabetes is often not the reason for admission, they often need a longer stay in hospital, are more likely to be re admitted and their risk of dying is higher. As well as the human cost, Type 2 diabetes treatment accounts for just under nine per cent of the annual NHS budget. This is around £8.8 billion a year. There are currently five million people in England at high risk of developing Type 2 diabetes. If these trends persist,

13

one in three people will be obese by 2034 and one in 10 will develop Type 2 diabetes. There is strong international evidence which demonstrates how behavioural interventions, which support people to maintain a healthy weight and be more active, can significantly reduce the risk of developing the condition. The Healthier You: NHS Diabetes Prevention Programme (NHS DPP) identifies those at high risk and refers them onto a behaviour change programme. The NHS DPP is a joint commitment from NHS England, Public Health England and Diabetes UK. We are currently piloting a digital stream of the NHS Diabetes Prevention Programme. NICE (2011). Type 2 diabetes prevention: population and community-level interventions PH35. Recommendations Definitions Types of intervention Guiding principles Whose health will benefit? Recommendation 1 Integrating national strategy on non-communicable diseases Recommendation 2 Local joint strategic needs assessments Recommendation 3 Developing a local strategy Recommendation 4 Interventions for communities at high risk of type 2 diabetes Recommendation 5 Conveying messages to the whole population Recommendation 6 Conveying messages to the local population Recommendation 7 Promoting a healthy diet: national action Recommendation 8 Promoting a healthy diet: local action Recommendation 9 Promoting physical activity: national action Recommendation 10 Promoting physical activity: local action Recommendation 11 Training those involved in promoting healthy lifestyles NICE (2012). Type 2 diabetes: prevention in people at high risk. 1.1 Risk assessment 1.2 Encouraging people to have a risk assessment 1.3 Risk identification (stage 1) 1.4 Risk identification (stage 2) 1.5 Matching interventions to risk 1.6 Reassessing risk 1.7 Commissioning risk identification and intensive lifestyle-change programmes 1.8 Quality-assured, intensive lifestyle-change programmes: design and delivery 1.9 Quality-assured, intensive lifestyle-change programmes: content 1.10 Quality-assured, intensive lifestyle-change programmes: evaluation 1.11 Raising awareness of the importance of physical activity 1.12 Providing tailored advice on physical activity 1.13 Weight management advice 1.14 Dietary advice 1.15 Vulnerable groups: information and services 1.16 Vulnerable groups: supporting lifestyle change 1.17 Intensive lifestyle-change programmes: quality assurance 1.18 Training and professional development 1.19 Metformin 1.20 Orlistat Public Health England (2015). A systematic review and metaanalysis assessing the effectiveness of pragmatic lifestyle interventions for the prevention of type 2 diabetes mellitus in routine practice. Introduction This review updated and extended a previously conducted systematic review and metaanalysis which assessed the effectiveness of ‘real-world’ interventions for the prevention of type 2 diabetes mellitus (T2DM) in high risk populations. This was achieved through the following research questions: 1. What is the effectiveness of diabetes prevention programmes on delaying the onset and reducing the incidence of T2DM and reducing weight and glucose in high risk populations in practice? 2. In which population groups are the models identified the most effective – age, gender, BMI and ethnicity? 3. What are the key identifiable elements across the most efficacious interventions that constitute a successful programme? Methods We updated the review by Dunkley et al. Further studies, published after July 2012 were identified via electronic searches of online published databases EMBASE, MEDLINE and The Cochrane Library. In addition, unpublished grey literature was considered for inclusion utilising the search engine Open Grey. We also contacted international and UK based experts within the field of diabetes prevention to collect previously unpublished data from both newly

14

completed research projects and from the evaluation of programmes that are currently active in England. Experimental and observational studies which considered the effectiveness of a lifestyle intervention, whether diet or physical activity alone or in combination, and whether standalone or compared to a control group; where the stated aim of the intervention was diabetes risk reduction or prevention of T2DM were included in the systematic review. In addition included studies all had a primary focus of translating evidence from previous diabetes efficacy trials into routine healthcare, or a community setting. For studies to be eligible for inclusion, they included adults (>18 years old) identified as being at high risk of developing T2DM (for example, obese, sedentary lifestyle, family history of diabetes, older age, metabolic syndrome, impaired glucose regulation, pre-diabetes, or elevated diabetes risk score); had a minimum follow-up of 12 months; and reported one of the outcomes of interest. The primary endpoint examined was incidence of T2DM at the latest time point at which it was reported in the study. Secondary endpoints assessed weight, HbA1c levels, fasting glucose and 2-hour glucose changes from baseline to between 12 to 18 months follow-up. Data was pooled using random effects models to take into account heterogeneity. Data was pooled in two ways: · to assess if diabetes prevention programmes work, the data from intervention arms from RCTs and non-RCTs was pooled · to assess the added benefit of diabetes prevention programmes over usual care, the data comparing the intervention arms to control from the RCTs only was assessed. To assess in whom the programmes work best and which programme elements are associated with success, we conducted a number of met regression and subgroup analyses. These analyses were conducted in the RCTs only, and assessed the difference between intervention and control. Results Data from 36 studies was included in this review. A total of 16 studies (18 intervention arms) reported incidence of T2DM. Of these 16 studies, 11 were RCTs consisting of 13 intervention vs. control comparisons. Weight change data at 12 to 18 months follow up was available for 35/36 studies (38 study arms, 20 were RCT intervention arms). Fasting glucose was reported across 24 studies (27 intervention arms), of which 14 studies (16 intervention arms) were RCTs. A total of 14 studies (15 intervention arms) reported changes in 2-hour glucose outcomes at 12-18 months follow up. Ten of the 15 intervention arms were from RCTs. HbA1c levels were available for ten studies (11 intervention arms), of which nine were RCT intervention arms. The incidence of T2DM was 75 cases per 1000 person years across all intervention arms. The pooled incidence rate of T2DM was 26% (95% Confidence Interval (CI): 7% to 42%) lower in those receiving a diabetes prevention programme compared with usual care. Attending a diabetes prevention programme corresponded to an overall 2.46kg mean weight loss at 12 to 18 months follow up. When compared with usual care the pooled mean weight loss was 1.57kg higher in those who received the intervention. The pooled reduction in fasting glucose was 0.09mmol/l across all arms. When compared with usual care there was a 0.06mmol/l greater reduction in fasting glucose; this was not statistically significant. The pooled reduction in 2-hour glucose was 0.38mmol/l. Across RCTs, the pooled reduction in 2-hour glucose was 0.28mmol/l in intervention arms when compared to control arms across RCTs. However this was not a significant reduction. The pooled reduction in HbA1c was 0.07 percentage-points. When comparing attending a diabetes prevention programme with usual care, an overall reduction in HbA1c of 0.04 percentage-points was seen. The mean age of participants at baseline or varying age inclusion criteria across studies was not significantly associated with incidence of T2DM, weight change or glucose outcomes. A one percentage-point increase in baseline percentage of males was found to be associated with a 3% higher incidence rate of T2DM and a borderline significant 0.05kg weight gain across intervention arms when compared with control arms. Studies which utilised BMI inclusion criteria of ≥25kg/m2 were associated with an additional 51% reduction in T2DM incidence and 3.07kg weight loss in prevention programme arms when compared with control arms, than studies which used no BMI inclusion criteria. The mean percentage of non-Caucasian participants at baseline or varying ethnic make-up of study participants was not significantly associated with incidence of T2DM, weight change or glucose outcomes. Some subgroups contained very few studies, so caution in interpretation is advised. Intervention content was coded in relation to the recommendations for lifestyle interventions for the prevention of diabetes provided by both the IMAGE project (Development and Implementation of a European Guideline and Training Standards for Diabetes prevention) and NICE. A one-point increase in NICE score resulted in a larger intervention effect on weight loss (-0.47kg) and decrease in fasting glucose levels (-0.03mmol/l), when compared with control arms. Adhering to 9 to 12 NICE guidelines resulted in an additional 3.24kg weight loss and 0.17mmol/l reduction in fasting glucose in intervention arms compared to usual care, than adhering to 5 to 8 guidelines. A one-point increase in IMAGE score resulted in a larger intervention effect on weight loss (-1.04kg) when compared to control arms. Scoring an IMAGE score of 5 to 6 also resulted in an added weight loss of 3.36kg in intervention arms in comparison with usual care than a score of up to 2 points. Utilising a combined diet and PA intervention was associated with greater weight loss of 1.93kgin intervention arms when compared with usual care, than using a PA only intervention. Spreading programme sessions across 9 to 18 months resulted in a 47% greater reduction in T2DM incidence rate in intervention arms than usual care, whilst not spreading the intervention across the same time-frame resulted in 2.32kg greater weight loss in intervention arms compared to usual care. Sessions of 1-2 hours in length resulted in an extra 2.20kg of weight loss in intervention arms compared to control arms, than using a session length of less than an hour. Offering 13 or more contacts over the first 18 months was associated with a 3.15kg greater weight

15

loss in intervention arms compared to control arms, than offering less than eight contacts. A one-hour increase in contact time corresponded to a 0.1kg greater weight loss in intervention arms compared to usual care. Providing 16 or more hours of contact time resulted in an additional 3.38kg weight loss and 0.18mmol/l decrease in fasting glucose in intervention arms. Studies offering only one contact produced a 0.02kg weight gain in intervention arms compared to usual care than providing weekly contacts. Providing bi-monthly contacts resulted in a smaller weight loss of 0.41kg and an increase in fasting glucose of 0.03mmol/l in intervention arms compared to usual care than weekly contact. Incorporating three or more behaviour change techniques into the prevention programme resulted in smaller reductions in 2-hour glucose in intervention arms (-0.15mmol/l) than using fewer than three techniques (-1.17mmol/l). Similarly use of self-regulatory techniques was associated with a smaller reduction in 2-hour glucose (-0.15mmol/l) in intervention arms when compared to usual care than not using such methods (-1.17mmol/l). Use of empathy building approaches was associated with a smaller weight loss (-0.80kg) and 2-hour glucose reduction (-0.03mmol/l) in prevention programme arms than not using these techniques (-2.73kg and - 0.77mmol/l respectively). Encouraging engagement of social support outside of intervention groups resulted in an additional 0.25mmol/l decrease in fasting glucose in intervention arms compared to control arms. RCT studies conducted outside of the UK reported 2.15kg greater weight loss as a result of intervention in comparison to usual care than those conducted in the UK (-0.21kg). Private intervention delivery corresponded to 5.50kg greater weight loss in intervention programme arms compared to control arms than primary care delivery. A group size of between 10 to 15 produced an additional 3.80kg weight loss in prevention programme arms compared to standard care than group sizes of less than ten (-0.71kg). Offering optional supervised PA sessions as part of the intervention produced a 1.17mmol/l greater decrease in 2-hour glucose in intervention arms compared to usual care than making PA recommendations alone. Use of calorie restriction targets produced a greater 3.92kg weight loss in intervention arms compared to usual care. Use of a risk score to identify individuals at high risk of T2DM was associated with a 39% increased incidence rate of T2DM in intervention arms in comparison to usual care, than using a glucose test. A one mmol/l increase in participant baseline fasting glucose resulted in a substantial 79% decrease in T2DM incidence rate in intervention arms when compared to control arms. Using an evidence base different to the major prevention programmes (DPS or DPP) resulted in smaller added weight loss in intervention arms (-0.24kg) when compared to using the DPP as the sole evidence base (-3.10kg) Conclusions Our review supports previous research, demonstrating that diabetes prevention programmes can significantly reduce the progression to T2DM and lead to reductions in weight and glucose compared with usual care. Those developing prevention programmes should adhere to the NICE and/or IMAGE guidelines to increase efficacy. Public Health England (2018). Health matters: preventing Type 2 Diabetes. This professional resource outlines how to optimise the NHS Diabetes Prevention Programme (NHS DPP) in order to identify those already found to be at risk of developing Type 2 diabetes and offer support that will help them reduce their risk of developing the disease. Scottish Government (2018). A healthier future: Scotland's diet and healthy weight delivery plan. A problem of this scale must be met with an equally ambitious aim, and our vision is for a Scotland where everyone eats well and has a healthy weight. Recognising the specific need to tackle weight-related issues at an early stage, this delivery plan also has an ambition to halve child obesity in Scotland by 2030. We are also aiming to significantly reduce health inequalities Scottish Government (2018). A Healthier Future: type 2 Diabetes prevention, early detection and intervention: framework. This framework has been developed to provide guidance to delivery partners as to the implementation of a specific weight management pathway for those ‘at risk’ or those diagnosed with type 2 diabetes. This pathway will sit within integrated weight management services and will require multidisciplinary and multi organisational teams to work together in partnership with the public to deliver a fully supported service. The framework will support our delivery partners in our shared aim of improved weight management services to support better outcomes for people across Scotland. The guidance in this framework sets out how Integrated Joint Boards (IJBS), NHS Boards and Community Planning Partners and other delivery partners should consider the various elements of providing a comprehensive weight management service with regards to type 2 diabetes. The actions here should be consider in conjunction with those set in the recently published ‘A Healthier Future – Scotland’s Diet and Healthy Weight Delivery Plan’

Cochrane Reviews

Hemmingsen B, Gimenez‐Perez G, Mauricio D, Roqué i Figuls M, Metzendorf MI,Richter B. Diet, physical activity or both for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk of developing type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2017;12):

16

- Background The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into a substantial health problem worldwide. Whether diet, physical activity or both can prevent or delay T2DM and its associated complications in at‐risk people is unknown. Objectives To assess the effects of diet, physical activity or both on the prevention or delay of T2DM and its associated complications in people at increased risk of developing T2DM. Search methods This is an update of the Cochrane Review published in 2008. We searched the CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, ICTRP Search Portal and reference lists of systematic reviews, articles and health technology assessment reports. The date of the last search of all databases was January 2017. We continuously used a MEDLINE email alert service to identify newly published studies using the same search strategy as described for MEDLINE up to September 2017. Selection criteria We included randomised controlled trials (RCTs) with a duration of two years or more. Data collection and analysis We used standard Cochrane methodology for data collection and analysis. We assessed the overall quality of the evidence using GRADE. Main results We included 12 RCTs randomising 5238 people. One trial contributed 41% of all participants. The duration of the interventions varied from two to six years. We judged none of the included trials at low risk of bias for all 'Risk of bias' domains. Eleven trials compared diet plus physical activity with standard or no treatment. Nine RCTs included participants with impaired glucose tolerance (IGT), one RCT included participants with IGT, impaired fasting blood glucose (IFG) or both, and one RCT included people with fasting glucose levels between 5.3 to 6.9 mmol/L. A total of 12 deaths occurred in 2049 participants in the diet plus physical activity groups compared with 10 in 2050 participants in the comparator groups (RR 1.12, 95% CI 0.50 to

2.50; 95% prediction interval 0.44 to 2.88; 4099 participants, 10 trials; very low‐quality evidence). The definition of T2DM incidence varied among the included trials. Altogether 315 of 2122 diet plus physical activity participants (14.8%) developed T2DM compared with 614 of 2389 comparator participants (25.7%)

(RR 0.57, 95% CI 0.50 to 0.64; 95% prediction interval 0.50 to 0.65; 4511 participants, 11 trials; moderate‐quality evidence). Two trials reported serious adverse events. In one trial no adverse events occurred. In the other trial one of 51 diet plus physical activity participants compared with none of 51 comparator participants experienced a serious adverse event (low‐quality evidence). Cardiovascular mortality was rarely reported (four of 1626 diet plus physical activity participants and four of 1637 comparator participants

(the RR ranged between 0.94 and 3.16; 3263 participants, 7 trials; very low‐quality evidence). Only one trial reported that no non‐fatal myocardial infarction or non‐fatal stroke had occurred (low‐quality evidence). Two trials reported that none of the participants had experienced hypoglycaemia. One trial investigated

health‐related quality of life in 2144 participants and noted that a minimal important difference between intervention groups was not reached (very low‐quality evidence). Three trials evaluated costs of the interventions in 2755 participants. The largest trial of these reported an analysis of costs from the health system perspective and society perspective reflecting USD 31,500 and USD 51,600 per quality‐adjusted

life year (QALY) with diet plus physical activity, respectively (low‐quality evidence). There were no data on blindness or end‐stage renal disease. One trial compared a diet‐only intervention with a physical‐activity intervention or standard treatment. The participants had IGT. Three of 130 participants in the diet group compared with none of the 141 participants in the physical activity group died (very low‐quality evidence).

None of the participants died because of cardiovascular disease (very ow‐quality evidence). Altogether 57 of 130 diet participants (43.8%) compared with 58 of 141 physical activity participants (41.1%) group

developed T2DM (very low‐quality evidence). No adverse events were recorded (very low‐quality evidence). There were no data on non‐fatal myocardial infarction, non‐fatal stroke, blindness, end‐stage renal disease, health‐related quality of life or socioeconomic effects. Two trials compared physical activity with standard treatment in 397 participants. One trial included participants with IGT, the other trial included participants with IGT, IFG or both. One trial reported that none of the 141 physical activity participants compared with three of 133 control participants died. The other trial reported that three of 84 physical

activity participants and one of 39 control participants died (very low‐quality evidence). In one trial T2DM developed in 58 of 141 physical activity participants (41.1%) compared with 90 of 133 control participants (67.7%). In the other trial 10 of 84 physical activity participants (11.9%) compared with seven of 39 control

participants (18%) developed T2DM (very low‐quality evidence). Serious adverse events were rarely reported (one trial noted no events, one trial described events in three of 66 physical activity participants

compared with one of 39 control participants ‐ very low‐quality evidence). Only one trial reported on cardiovascular mortality (none of 274 participants died ‐ very low‐quality evidence). Non‐fatal myocardial infarction or stroke were rarely observed in the one trial randomising 123 participants (very low‐quality evidence). One trial reported that none of the participants in the trial experienced hypoglycaemia. One trial investigating health‐related quality of life in 123 participants showed no substantial differences between

intervention groups (very low‐quality evidence). There were no data on blindness or socioeconomic effects. Authors' conclusions There is no firm evidence that diet alone or physical activity alone compared to standard treatment influences the risk of T2DM and especially its associated complications in people at increased risk of developing T2DM. However, diet plus physical activity reduces or delays the incidence of T2DM in people with IGT. Data are lacking for the effect of diet plus physical activity for people with

intermediate hyperglycaemia defined by other glycaemic variables. Most RCTs did not investigate patient‐important outcomes. Plain language summary Diet, physical activity or both for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk Review question Are diet or

17

physical activity, or both able to prevent or delay the development of type 2 diabetes and its associated

complications in at‐risk people? Background People with moderately elevated blood glucose (often referred to as 'prediabetes') are said to be at an increased risk of developing type 2 diabetes. It is currently recommended that all people with increased risk of developing type 2 diabetes should adjust their eating habits and physical activity levels. We wanted to find out whether these changes in diet, physical activity or both could prevent or delay type 2 diabetes in people at increased risk. We also wanted to know the effects

on patient‐important outcomes, such as complications of diabetes (e.g. kidney and eye disease, heart attack, stroke), death from any cause, health‐related quality of life (a measure of a person’s satisfaction with their life and health) and side‐effects. Study characteristics Participants had to have blood glucose levels higher than considered normal, but below the glucose levels that are used to diagnose type 2 diabetes mellitus. We found 12 randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) with 5238 participants. The duration of the treatments varied from two years to six years. Most trials included people defined as being at increased risk of type 2 diabetes based on glucose levels measured two hours after ingestion of 75 g of glucose (i.e. 'impaired glucose tolerance' (IGT) after an oral glucose tolerance test). This evidence is up to date as of January 2017. We used a MEDLINE email alert service to identify newly published studies up to September 2017. Key results One study compared diet only with physical activity only. Fifty‐seven of 130 participants (44%)

in the diet‐only group compared with 58 of 141 participants (41%) in the physical activity‐only group developed type 2 diabetes. Two studies compared physical activity with standard treatment; in one study 58 of 141 participants (41%) in the physical activity group compared with 90 of 133 participants (68%) in the control group developed type 2 diabetes; in the other study 10 of 84 participants (12%) in the physical activity group compared with seven out of 39 participants (18%) in the control group developed type 2 diabetes. Eleven studies compared diet plus physical activity with standard or no treatment. Diet plus physical activity decreased the risk of developing type 2 diabetes, which occurred in 315 of 2122 participants (15%) in the diet plus physical activity group compared with 614 of 2389 participants (26%) in the standard treatment group. We detected neither an advantage nor a disadvantage of diet, physical activity or both with regard to heart attacks or strokes. Our included studies did not report on complications

of diabetes such as kidney or eye disease. The effects on health‐related quality of life were inconclusive. Very few participants died in the course of the studies and side‐effects were also rare. Future long‐term

studies should investigate more patient‐important outcomes like complications of diabetes, because we do not know for sure whether ’prediabetes’ is just a condition arbitrarily defined by a laboratory measurement or is, in fact, a real risk factor for type 2 diabetes mellitus and whether treatment of this condition translates

into better patient‐important outcomes. Quality of the evidence All included trials had deficiencies in the way that they were conducted or how key items were reported. For diet plus physical activity compared with standard treatment, we found rather good evidence that the development of new type 2 diabetes was reduced or delayed. For the other comparisons the number of participants was small, resulting in a high risk of random errors (play of chance).

Hemmingsen B, Krogh J, Metzendorf MI,Richter B. Sodium‐glucose cotransporter (SGLT) 2 inhibitors for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2016;4):

- Background Sodium‐glucose cotransporter (SGLT) 2 inhibitors were recently approved as glucose‐lowering interventions in people with type 2 diabetes mellitus (T2DM). Potential beneficial or harmful effects of SGLT 2 inhibitors in people at risk for the development of T2DM are unknown. Objectives To assess the effects of SGLT 2 inhibitors focusing on the prevention or delay of T2DM and its associated complications in people with impaired glucose tolerance, impaired fasting blood glucose or moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these. Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, PubMed, EMBASE, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) and reference lists of systematic reviews, articles and health technology assessment reports. We asked investigators of ongoing for information about additional trials. The date of the last search of all databases was January 2016. Selection criteria Randomised controlled trials (RCTs) of any duration

comparing SGLT 2 inhibitors with any glucose‐lowering intervention, behaviour‐changing intervention, placebo or no intervention in people with impaired fasting glucose, impaired glucose tolerance, moderately elevated HbA1c or combinations of these. Data collection and analysis Two review authors read all abstracts, assessed quality and extracted data independently. We resolved discrepancies by consensus or the involvement of a third author. Main results We could not include any RCT in this systematic review. One trial was published in two abstracts, but did not provide separate information of the participants with impaired glucose tolerance, impaired fasting glucose or both. We identified two ongoing trials, both evaluating the effects of dapagliflozin (and metformin) in people at risk for the development of type 2

diabetes and a follow‐up of 24 to 26 weeks. Both trials will mainly report on surrogate outcome measures with some data on adverse effects and health‐related quality of life. Authors' conclusions Due to lack of data it is not possible to conclude whether SGLT 2 inhibitors prevent or delay the diagnosis of T2DM and

its associated complications. Plain language summary Sodium‐glucose cotransporter (SGLT) 2 inhibitors

18

for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the

development of type 2 diabetes mellitus Review question What are the effects of the group of glucose‐lowering drugs called 'sodium‐glucose cotransporter (SGLT) 2 inhibitors' for prevention or delay of type 2 diabetes mellitus and its associated complications in people at risk for the development of type 2 diabetes mellitus? Background The SGLT 2 inhibitors (such as canagliflozin, dapagliflozin and empagliflozin) are

glucose‐lowering drugs that reduce blood glucose levels by increasing the secretion of glucose from the kidneys to the urine. SGLT 2 inhibitors were recently approved for the treatment of diabetes in people with type 2 diabetes mellitus. It is currently not known whether SGLT 2 inhibitors should be prescribed for people with raised blood glucose levels who do not meet the criteria for having type 2 diabetes. We wanted to find out whether these drugs would prevent or only delay the development of type 2 diabetes.

Furthermore, we wanted to analyse the effects of SGLT 2 inhibitors on patient‐important outcomes such as complications of diabetes (for example kidney and eye disease, heart attacks, strokes), death from any

cause, health‐related quality of life and side effects of the medications. Study characteristics We searched the medical literature and registers of ongoing trials for randomised controlled trials (clinical studies where people are randomly put into one of two or more treatment groups) of SGLT 2 inhibitors for prevention or delay of type 2 diabetes mellit s and its associated complications. We wanted to synthesise the findings of several studies to answer our review question. Unfortunately, we did not find such a study. This evidence is up to date as of January 2016. Key results We could not include any study in our systematic review. However, we identified two ongoing studies, both evaluating the effects of dapagliflozin in people at risk for

the development of type 2 diabetes and a follow‐up of 24 to 26 weeks. Both rather short‐term studies will mainly report on laboratory outcome measures with some data on side effects and health‐related quality of life. Quality of the evidence Because we could not include any study we were not able to investigate the quality of the evidence. In both ongoing studies the participants know what kind of medication they are taking which may create problems with the measurement of some outcomes such as health‐related quality of life and side effects.

Norris SL, Zhang X, Avenell A, Gregg E, Brown T, Schmid CH, et al. Long‐term non‐pharmacological weight loss interventions for adults with type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2005;2): - Background Most persons with type 2 diabetes are overweight and obesity worsens the metabolic and

physiologic abnormalities associated with diabetes. Objectives The objective of this review is to assess the effectiveness of lifestyle and behavioral weight loss and weight control interventions for adults with type 2 diabetes. Search methods Studies were obtained from computerized searches of multiple electronic bibliographic databases, supplemented with hand searches of selected journals and consultation with experts in obesity research. Selection criteria Studies were included if they were published or unpublished randomized controlled trials in any language, and examined weight loss or weight control strategies using one or more dietary, physical activity, or behavioral interventions, with a follow‐up interval of at least 12 months. Data collection and analysis Effects were combined using a random effects model. Main results The 22 studies of weight loss interventions identified had a 4,659 participants and follow‐up of 1 to 5 years. The pooled weight loss for any intervention in comparison to usual care among 585 subjects was 1.7 kg (95 % confidence interval [CI] 0.3 to 3.2), or 3.1% of baseline body weight among 517 subjects. Other main comparisons demonstrated non significant results: among 126 persons receiving a physical activity and

behavioral intervention, those who also received a very low calorie diet lost 3.0 kg (95% CI ‐0.5 to 6.4), or 1.6% of baseline body weight, more than persons receiving a low‐calorie diet. Among 53 persons receiving identical dietary and behavioral interventions, those receiving more intense physical activity interventions lost 3.9 kg (95% CI ‐1.9 to 9.7), or 3.6% of baseline body weight, more than those receiving a less intense or no physical activity intervention. Comparison groups often achieved significant weight loss (up to 10.0 kg), minimizing between‐group differences. Changes in glycated hemoglobin generally corresponded to

changes in weight and were not significant when between‐group differences were examined. No data were identified on quality of life and mortality. Authors' conclusions Weight loss strategies using dietary, physical

activity, or behavioral interventions produced small between‐group improvements in weight. These results were minimized by weight loss in the comparison group, however, and examination of individual study arms revealed that multicomponent interventions including very low calorie diets or low calorie diets may hold promise for achieving weight loss in adults with type 2 diabetes. Plain language summary Long‐term

non‐pharmacological weight loss interventions for adults with type 2 diabetes mellitus Most persons with type 2 diabetes are overweight, and the health of these persons can be improved with weight loss. Weight

loss is very difficult to achieve in the long‐term, however, particularly among persons with diabetes. This systematic review of diet, physical activity, and behavioral interventions for weight loss, revealed a decrease in weight of 1.7 kg at one year or more. These results were minimized by weight loss in the comparison group, however. No data were identified on quality of life or mortality.

Norris SL, Zhang X, Avenell A, Gregg E, Schmid CH,Lau J. Long‐term non‐pharmacological weight loss interventions for adults with prediabetes. Cochrane Database of Systematic Reviews 2005;2): - Background Most persons with prediabetes (impaired glucose tolerance or impaired fasting glucose) are

overweight, and obesity worsens the metabolic and physiologic abnormalities associated with this

19

condition. Prediabetes is an important risk factor for the development of type 2 diabetes. Objectives The objective of this review was to assess the effectiveness of dietary, physical activity, and behavioral weight loss, and weight control interventions for adults with prediabetes. Search methods Studies were obtained from computerized searches of multiple electronic bibliographic dababases, supplemented by hand searches of selected journals, and consultation with experts in obesity research. The last search was conducted May, 2004. Selection criteria Studies were included if they were published or unpublished randomized controlled trials in any language and examined weight loss or weight control strategies using

one or more dietary, physical activity, or behavioral interventions, with a follow‐up interval of at least 12 months. Data collection and analysis Effects were combined using a random‐effects model. Main results Nine studies were identified, with a total of 5,168 participants. Follow‐up ranged from 1 to 10 years. Quantitative synthesis was limited by the heterogeneity of populations, settings, and interventions and by the small number of studies that examined outcomes other than weight. Overall, in comparisons with usual

care, four studies with a follow‐up of one year reduced weight by 2.8 kg (95 % confidence interval (CI) 1.0 to 4.7) (3.3% of baseline body weight) and decreased body mass index by 1.3 kg/m 2 (95% CI 0.8 to 1.9). Weight loss at two years was 2.6 kg (95% CI 1.9 to 3.3) (three studies). Modest improvements were noted in the few studies that examined glycemic control, blood pressure, or lipid concentrations (P > 0.05). No data on quality of life or mortality were found. The incidence of diabetes was significantly lower in the intervention groups versus the controls in three of five studies examining this outcome at 3 to 6 years

follow‐up. Authors' conclusions Overall, weight loss strategies using dietary, physical activity, or behavioral interventions produced significant improvements in weight among persons with prediabetes and a

significant decrease in diabetes incidence. Further work is needed on the long‐term effects of these interventions on morbidity and mortality and on how to implement these interventions in diverse community

settings. Plain language summary Long‐term non‐pharmacological weight loss interventions for adults with prediabetes Persons with blood glucose levels that are abnormal, but not in the range of persons with diabetes, are said to have prediabetes, which often precedes the development of type 2 diabetes. Most persons with prediabetes are overweight and obesity worsens the blood glucose and other problems associated with prediabetes. In this review we found that dietary, physical activity, or behavioral interventions produced significant improvements in weight among persons with prediabetes and a significant decrease in diabetes incidence. Modest, but not statistically significant improvements were noted in the few studies that examined blood sugar control, blood pressure, and lipid levels. No data on quality of life or mortality were found.

Norris SL, Zhang X, Avenell A, Gregg E, Schmid CH,Lau J. Pharmacotherapy for weight loss in adults with type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2005;1): - Background Obesity is closely related to type 2 diabetes and long‐term weight reduction is an important

part of the care delivered to obese persons with diabetes. Objectives To assess the efficacy of pharmacotherapy for weight loss in adults with type 2 diabetes. Search methods Computerized searches were performed of MEDLINE, EMBASE, Web of Science and other electronic bibliographic databases, supplemented with hand searches of reference lists and selected journals. Selection criteria Randomized, controlled trials were included where pharmacotherapy was used as the primary strategy for weight loss among adults with type 2 diabetes. Published and unpublished literature in any language and with any study design was included. Data collection and analysis Two reviewers abstracted data and the quality of included studies was evaluated by assessing potential attrition, as well as selection and measurement bias, and a Jadad score was obtained. Effects were combined using a random effects model. Main results A sufficient number of studies were available for a quantitative synthesis for fluoxetine, orlistat, and sibutramine. Twenty two randomized controlled trials were included in the review, with a total of 296 participants for fluoxitine, 2036 for orlistat, and 1047 for sibutramine. Pharmacotherapy produced modest

reductions in weight for fluoxetine (5.1 kg (95% confidence interval [CI], 3.3 ‐ 6.9) at 24 to 26 weeks follow up; orlistat 2.0 kg (CI, 1.3 ‐ 2.8) at 12 to 57 weeks follow‐up, and sibutramine 5.1 kg (CI, 3.2 ‐ 7.0) at 12 to 52 weeks follow‐up. Glycated hemoglobin also modestly and significantly reduced for fluoxetine and orlistat. Gastrointestinal side effects were common with orlistat; tremor, somnolence and sweating with fluoxetine; and palpitations with sibutramine. Some studies, using a variety of study designs, were available on other drugs and a significant decrease in weight was noted in three studies of mazindol, one of phenmetrazine, two of phentermine. No studies were identified that fit inclusion criteria for pseudoephedrine, ephedra, sertraline, yohimbine, amphetamine or its derivatives, bupropion, topiramate, benzocaine, threachlorocitric acid, sertraline, and bromocriptine. Authors' conclusions Fluoxetine, orlistat, and sibutramine can achieve statistically significant weight loss over 12 to 57 weeks. The magnitude of weight loss is modest, however, and the long‐term health benefits remain unclear. The safety of sibutramine is uncertain. There is a paucity of data on other drugs for weight loss or control in persons with type 2 diabetes. Plain language summary Pharmacotherapy for weight loss in adults with type 2 diabetes mellitus Obesity is closely related to type 2 diabetes and weight reduction is an important part of the care delivered to obese persons with diabetes. This review of drugs for weight loss among adults with type 2 diabetes revealed weight loss of between 2.0 and 5.1 kg for fluoxetine, orlistat and sibutramine at follow‐up

of up to 57 weeks. The long‐term effects remain uncertain. Adverse events were common in all three

20

drugs: gastrointestinal side effects with orlistat; tremor, somnolence, and sweating with fluoxetine; and palpitations with sibutramine. There were few studies examining other drugs used for weight loss in populations with diabetes.

Pappas Y, Wei I, Car J, Majeed A,Sheikh A. Computer‐assisted versus oral‐and‐written family history taking for identifying people with elevated risk of type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2011;12): - Background Diabetes is a chronic illness characterised by insulin resistance or deficiency, resulting in

elevated glycosylated haemoglobin A1c (HbA1c) levels. Because diabetes tends to run in families, the collection of data is an important tool for identifying people with elevated risk of type2 diabetes. Traditionally, oral‐and‐written data collection methods are employed but computer‐assisted history taking systems (CAHTS) are increasingly used. Although CAHTS were first described in the 1960s, there remains uncertainty about the impact of these methods on family history taking, clinical care and patient outcomes

such as health‐related quality of life. Objectives To assess the effectiveness of computer‐assisted versus oral‐and‐written family history taking for identifying people with elevated risk of developing type 2 diabetes mellitus. Search methods We searched The Cochrane Library (issue 6, 2011), MEDLINE (January 1985 to June 2011), EMBASE (January 1980 to June 2011) and CINAHL (January 1981 to June 2011). Reference lists of obtained articles were also pursued further and no limits were imposed on languages and

publication status. Selection criteria Randomised controlled trials of computer‐assisted versus oral‐and‐written history taking in adult participants (16 years and older). Data collection and analysis Two authors independently scanned the title and abstract of retrieved articles. Potentially relevant articles were investigated as full text. Studies that met the inclusion criteria were abstracted for relevant population and intervention characteristics with any disagreements resolved by discussion, or by a third party. Risk of bias

was similarly assessed independently. Main results We found no controlled trials on computer‐assisted versus oral‐and‐written family history taking for identifying people with elevated risk of type 2 diabetes mellitus. Authors' conclusions There is a need to develop an evidence base to support the effective

development and use of computer‐assisted history taking systems in this area of practice. In the absence

of evidence on effectiveness, the implementation of computer‐assisted family history taking for identifying people with elevated risk of type 2 diabetes may only rely on the clinicians' tacit knowledge, published

monographs and viewpoint articles. Plain language summary Computer‐assisted versus oral‐and‐written family history taking for identifying people with elevated risk of type 2 diabetes mellitus We know that diabetes runs in families. For this reason, healthcare professionals routinely take family histories to help them identify people who are at high risk of developing diabetes. Patient histories may be recorded

manually by using oral‐and‐written methods or via a computer‐assisted history taking system. Computer‐assisted history taking systems can be used by healthcare professionals, or directly by patients, as in the

case of, for example, pre‐consultation interviews. They can be used remotely, for example via the Internet, telephone or on‐site. They draw on a range of technologies such as personal computers, personal digital assistants, mobile phones and electronic kiosks; data input can be mediated via, amongst others, keyboards, touch screens and voice‐recognition software. Although computer‐assisted history taking methods were first used in the 1960s we are still not certain about their effects on history taking in people with a high risk to develop diabetes. Therefore, we reviewed the literature to find studies that compare the

effects of oral‐and‐written methods to those of computer‐assisted family history taking on the quality of collected data as well as on allowing us to identify people who are at risk of developing diabetes. In this occasion we found no randomised controlled trials that investigated the above. We therefore suggest that more primary research is required in this area to allow an informed decision to be made by physicians, patients and policymakers.

Priebe M, van Binsbergen J, de Vos R,Vonk RJ. Whole grain foods for the prevention of type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2008;1): - Background Diet as one aspect of lifestyle is thought to be one of the modifiable risk factors for the

development of type 2 diabetes mellitus (T2DM). Information is needed as to which components of the diet could be protective for this disease. Objectives To asses the effects of whole‐grain foods for the prevention of T2DM. Search methods We searched CENTRAL, MEDLINE, EMBASE, CINAHL and AMED. Selection criteria We selected cohort studies with a minimum duration of five years that assessed the association

between intake of whole‐grain foods or cereal fibre and incidence of T2DM. Randomised controlled trials lasting at least six weeks were selected that assessed the effect of a diet rich in whole‐grain foods compared to a diet rich in refined grain foods on T2DM and its major risk factors. Data collection and analysis Two authors independently selected the studies, assessed study quality and extracted data. Data of studies were not pooled because of methodological diversity. Main results One randomised controlled trial and eleven prospective cohort studies were identified. The randomised controlled trial, which was of low methodological quality, reported the change in insulin sensitivity in 12 obese hyperinsulinemic

participants after six‐week long interventions. Intake of whole grain foods resulted in a slight improvement of insulin sensitivity and no adverse effects. Patient satisfaction, health related quality of life, total mortality

and morbidity was not reported. Four of the eleven cohort studies measured cereal fibre intake, three

21

studies whole grain intake and two studies both. Two studies measured the change in whole grain food intake and one of them also change in cereal fibre intake. The incidence of T2DM was assessed in nine studies and changes in weight gain in two studies. The prospective studies consistently showed a reduced risk for high intake of whole grain foods (27% to 30%) or cereal fibre (28% to 37%) on the development of T2DM. Authors' conclusions The evidence from only prospective cohort trials is considered to be too weak to be able to draw a definite conclusion about the preventive effect of whole grain foods on the

development of T2DM. Properly designed long‐term randomised controlled trials are needed. To facilitate this, further mechanistic research should focus on finding a set of relevant intermediate endpoints for T2DM and on identifying genetic subgroups of the population at risk that are most susceptible to dietary intervention. Plain language summary Whole grain foods for the prevention of type 2 diabetes mellitus Food products derived from cereal grains as wheat, rice, corn, rye, oat, and barley constitute a major part

of the daily diet in many countries. In refined‐grain products, the bran and germ of the grain, which contain the major amount of nutrients and dietary fibre, have been removed and only the starchy inner part of the grain (ca. 80% of the whole grain) is used. Whole grain foods contain either intact, flaked or broken grain

kernels, coarsely ground kernels or flour that is made from whole grains (whole‐meal flour). In this review the effect of whole grain foods and cereal fibre (as a marker of whole‐grain food intake) on the prevention of type 2 diabetes mellitus (T2DM) was assessed using all available prospective cohort studies and randomised controlled trials. Only one randomised controlled trial was found which was of low methodological quality. This study investigated in 12 overweight persons during six weeks the effect of the consumption of refined grain foods versus that of whole grain foods on insulin sensitivity (risk factor for the development of T2DM). Intake of whole grain foods resulted in a slight improvement of insulin sensitivity, increased bowel movements and no adverse effects. No information was given about patient satisfaction, health related quality of life, total mortality and morbidity. In addition eleven prospective cohort studies were found. One study was conducted in Finland and the rest in the United States of merica of which seven were done in health care workers. Some of the studies were of limited quality. They consistently showed that a high intake of whole grain foods or cereal fibre is associated with a lower risk of the development of T2DM. However, evidence for a protective effect coming from prospective cohort studies only has to be considered as weak as with this design no cause and effect relationship can be established. Well‐designed randomised controlled trials are needed to be able to draw definite conclusions about the preventive effects of whole grain consumption on development of T2DM.

Thomas D, Elliott EJ,Baur L. Low glycaemic index or low glycaemic load diets for overweight and obesity. Cochrane Database of Systematic Reviews 2007;3): - Background Obesity is increasingly prevalent, yet the nutritional management remains contentious. It has

been suggested that low glycaemic index or load diets may stimulate greater weight loss than higher glycaemic index or load diets or other weight reduction diets. Objectives To assess the effects of low glycaemic index or load diets for weight loss in overweight or obese people. Search methods Trials were identified through The Cochrane Library , MEDLINE, EMBASE, CINAHL and manual searches of bibliographies. Selection criteria Randomised controlled trials comparing a low glycaemic index or load diet (LGI) with a higher glycaemic index or load diet or other diet (Cdiet) in overweight or obese people. Data collection and analysis Two authors independently selected trials, assessed quality and extracted data, including any information provided on adverse effects. Main results We identified six eligible randomised controlled trials (total of 202 participants). Interventions ranged from five weeks to six months duration with

up to six months follow‐up after the intervention ceased. The decrease in body mass (WMD ‐1.1 kg, 95% confidence interval (CI) ‐2.0 to ‐0.2, P < 0.05) (n = 163), total fat mass (WMD ‐1.1 kg, 95% CI ‐1.9 to ‐0.4, P < 0.05) (n =147) and body mass index (WMD ‐1.3, 95% CI ‐2.0 to ‐0.5, P < 0.05) (n = 48) was significantly greater in participants receiving LGI compared to Cdiets. The decrease in total cholesterol was

significantly greater with LGI compared to Cdiets (WMD ‐0.22 mmol/L, 95% CI ‐0.43 to ‐0.02, P < 0.05), as was the change in LDL‐cholesterol (WMD ‐0.24 mmol/L, 95% CI ‐0.44 to ‐0.05, P < 0.05). No study reported adverse effects, mortality or quality of life data. Authors' conclusions Overweight or obese people on LGI lost more weight and had more improvement in lipid profiles than those receiving Cdiets. Body

mass, total fat mass, body mass index, total cholesterol and LDL‐cholesterol all decreased significantly more in the LGI group. In studies comparing ad libitum LGI diets to conventional restricted energy low‐fat diets, participants fared as well or better on th LGI diet, even though they could eat as much as desired. Lowering the glycaemic load of the diet appears to be an effective method of promoting weight loss and improving lipid profiles and can be simply incorporated into a person's lifestyle. Further research with longer term follow‐up will determine whether improvement continues long‐term and improves quality of life. Plain language summary Low glycaemic index or low glycaemic load diets for overweight and obesity There is a lack of consensus as to the best nutritional management of obesity. We assessed the effects of low glycaemic index or glycaemic load diets in overweight or obese people. Six randomised controlled trials, involving 202 participants, were analysed. Interventions ranged from five weeks to six months duration. Participants receiving the low glycaemic index or load diet lost a mean of one kilogramme more than those on comparison diets. Lipid profile also improved more in participants receiving the low glycaemic index or load diet. No study reported adverse effects, mortality or quality of life data.

22

Thomas D, Elliott EJ,Naughton GA. Exercise for type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2006;3): - Background Exercise is generally recommended for people with type 2 diabetes mellitus. However, some

studies evaluate an exercise intervention including diet or behaviour modification or both, and the effects of diet and exercise are not differentiated. Some exercise studies involve low participant numbers, lacking power to show significant differences which may appear in larger trials. Objectives To assess the effects of exercise in type 2 diabetes mellitus. Search methods Trials were identified through the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and manual searches of bibliographies.

Selection criteria All randomised controlled trials comparing any type of well‐documented aerobic, fitness or progressive resistance training exercise with no exercise in people with type 2 diabetes mellitus. Data collection and analysis Two authors independently selected trials, assessed trial quality and extracted data. Study authors were contacted for additional information. Any information on adverse effects was collected from the trials. Main results Fourteen randomised controlled trials comparing exercise against no exercise in type 2 diabetes were identified involving 377 participants. Trials ranged from eight weeks to twelve months duration. Compared with the control, the exercise intervention significantly improved glycaemic

control as indicated by a decrease in glycated haemoglobin levels of 0.6% (‐0.6 % HbA 1c , 95%

confidence interval (CI) ‐0.9 to ‐0.3; P < 0.05). This result is both statistically and clinically significant. There was no significant difference between groups in whole body mass, probably due to an increase in fat free mass (muscle) with exercise, as reported in one trial (6.3 kg, 95% CI 0.0 to 12.6). There was a reduction in visceral adipose tissue with exercise (‐45.5 cm 2 , 95% CI ‐63.8 to ‐27.3), and subcutaneous adipose tissue also decreased. No study reported adverse effects in the exercise group or diabetic complications. The exercise intervention significantly increased insulin response (131 AUC, 95% CI 20 to

242) (one trial), and decreased plasma triglycerides (‐0.25 mmol/L, 95% CI ‐0.48 to ‐0.02). No significant difference was found between groups in quality of life (one trial), plasma cholesterol or blood pressure.

Authors' conclusions The meta‐analysis shows that exercise significantly improves glycaemic control and reduces visceral adipose tissue and plasma triglycerides, but not plasma cholesterol, in people with type 2 diabetes, even without weight loss. Plain language summary Exercise for type 2 diabetes mellitus Exercise, dietary changes and medications are frequently used in the management of type 2 diabetes. However, it is difficult to determine the independent effect of exercise from some trials because exercise has been combined with dietary modifications or medications, or compared with a control which includes another form of intervention. The review authors aimed to determine the effect of exercise on blood sugar control in type 2 diabetes. This review found that exercise improves blood sugar control and that this effect is evident even without weight loss. Furthermore, exercise decreases body fat content, thus the failure to lose weight with exercise programmes is probably explained by the conversion of fat to muscle. Exercise improved the body's reaction to insulin and decreased blood lipids. Quality of life was only assessed in one study, which found no difference between the two groups. No significant difference was found between groups in blood levels of cholesterol or blood pressure. A total of 14 randomised controlled trials were assessed. These included 377 participants and compared groups that differed only with respect to an exercise programme intervention. The duration of the interventions in the studies ranged from eight weeks to one year. Two studies reported follow‐up information, one at six months after the end of the six month

exercise intervention and one at twelve months post‐intervention. Gener lly, the studies were well‐conducted, but blinding of outcome assessors was not reported and although all studies reported that

randomisation was performed, few gave details of the method. No adverse effects with exercise were

reported. The effect of exercise on diabetic complications was not assessed in any of the studies. The relatively short duration of trials prevented the reporting of any significant long term complications or mortality. Another limitation was the small number of participants included in the analyses for adiposity, blood pressure, cholesterol, body's muscle and quality of life.

Other Reviews

Aguiar EJ, Morgan PJ, Collins CE, Plotnikoff RC,Callister R. Efficacy of interventions that include diet, aerobic and resistance training components for type 2 diabetes prevention: a systematic review with meta-analysis. International Journal of Behavioral Nutrition & Physical Activity 2014;11(2 Current recommendations for the prevention of type 2 diabetes advise modification of diet and exercise

behaviors including both aerobic and resistance training. However, the efficacy of multi-component interventions involving a combination of these three components has not been established. The aims of this review were to systematically review and meta-analyze the evidence on multi-component (diet+aerobic exercise+resistance training) lifestyle interventions for type 2 diabetes prevention. Eight electronic databases (Medline, Embase, SportDiscus, Web of Science, CINAHL, Informit health collection, Cochrane library and Scopus) were searched up to June 2013. Eligible studies 1) recruited prediabetic adults or individuals at risk of type 2 diabetes; 2) conducted diet and exercise [including both physical

23

activity/aerobic and resistance training] programs; and 3) reported weight and plasma glucose outcomes. In total, 23 articles from eight studies were eligible including five randomized controlled trials, one quasi-experimental, one two-group comparison and one single-group pre-post study. Four studies had a low risk of bias (score>=6/10). Median intervention length was 12 months (range 4-48 months) with a follow-up of 18 months (range 6.5-48 months). The diet and exercise interventions varied slightly in terms of their specific prescriptions. Meta-analysis favored interventions over controls for weight loss (-3.79 kg [-6.13, -1.46; 95% CI], Z=3.19, P=0.001) and fasting plasma glucose (-0.13 mmol.L-1 [-0.24, -0.02; 95% CI], Z=2.42, P=0.02). Diabetes incidence was only reported in two studies, with reductions of 58% and 56% versus control groups. In summary, multi-component lifestyle type 2 diabetes prevention interventions that include diet and both aerobic and resistance exercise training are modestly effective in inducing weight loss and improving impaired fasting glucose, glucose tolerance, dietary and exercise outcomes in at risk and prediabetic adult populations. These results support the current exercise guidelines for the inclusion of resistance training in type 2 diabetes prevention, however there remains a need for more rigorous studies, with long-term follow-up evaluating program efficacy, muscular fitness outcomes, diabetes incidence and risk reduction.

Aziz Z, Absetz P, Oldroyd J, Pronk NP,Oldenburg B. A systematic review of real-world diabetes prevention programs: learnings from the last 15 years. Implementation Science 2015;10(172 BACKGROUND: The evidence base for the prevention of type 2 diabetes mellitus (T2DM) has progressed

rapidly from efficacy trials to real-world translational studies and practical implementation trials over the last 15 years. However, evidence for the effective implementation and translation of diabetes programs and their population impact needs to be established in ways that are different from measuring program effectiveness. We report the findings of a systematic review that focuses on identifying the critical success factors for implementing diabetes prevention programs in real-world settings.

METHODS: A systematic review of programs aimed at diabetes prevention was undertaken in order to evaluate their outcomes using the penetration, implementation, participation, and effectiveness (PIPE) impact metric. A search for relevant articles was carried out using PubMed (March 2015) and Web of Science, MEDLINE, CENTRAL, and EMBASE. A quality coding system was developed and included studies were rated independently by three researchers.

RESULTS: Thirty eight studies were included in the review. Almost all (92 %) provided details on participation; however, only 18 % reported the coverage of their target population (penetration). Program intensity or implementation-as measured by frequency of contacts during first year and intervention duration-was identified in all of the reported studies, and 84 % of the studies also reported implementation fidelity; however, only 18 % of studies employed quality assurance measures to assess the extent to which the program was delivered as planned. Sixteen and 26 % of studies reported 'highly' or 'moderately' positive changes (effectiveness) respectively, based on weight loss. Six (16 %) studies reported 'high' diabetes risk reduction but 'low' to 'moderate' weight loss only.

CONCLUSION: Our findings identify that program intensity plays a major role in weight loss outcomes. However, programs that have high uptake-both in terms of good coverage of invitees and their willingness to accept the invitation-can still have considerable impact in lowering diabetes risk in a population, even with a low intensity intervention that only leads to low or moderate weight loss. From a public health perspective, this is an important finding, especially for resource constrained settings. More use of the PIPE framework components will facilitate increased uptake of T2DM prevention programs around the world.

Barry E, Roberts S, Oke J, Vijayaraghavan S, Normansell R,Greenhalgh T. Efficacy and effectiveness of screen and treat policies in prevention of type 2 diabetes: systematic review and meta-analysis of screening tests and interventions. BMJ 2017;356(i6538 OBJECTIVES: To assess diagnostic accuracy of screening tests for pre-diabetes and efficacy of

interventions (lifestyle or metformin) in preventing onset of type 2 diabetes in people with pre-diabetes. DESIGN: Systematic review and meta-analysis. DATA SOURCES AND METHOD: Medline, PreMedline, and Embase. Study protocols and seminal papers were

citation-tracked in Google Scholar to identify definitive trials and additional publications. Data on study design, methods, and findings were extracted onto Excel spreadsheets; a 20% sample was checked by a second researcher. Data extracted for screening tests included diagnostic accuracy and population prevalence. Two meta-analyses were performed, one summarising accuracy of screening tests (with the oral glucose tolerance test as the standard) for identification of pre-diabetes, and the other assessing relative risk of progression to type 2 diabetes after either lifestyle intervention or treatment with metformin.

ELIGIBILITY CRITERIA: Empirical studies evaluating accuracy of tests for identification of pre-diabetes. Interventions (randomised trials and interventional studies) with a control group in people identified through screening. No language restrictions.

RESULTS: 2874 titles were scanned and 148 papers (covering 138 studies) reviewed in full. The final analysis included 49 studies of screening tests (five of which were prevalence studies) and 50 intervention trials. HbA_1c had a mean sensitivity of 0.49 (95% confidence interval 0.40 to 0.58) and specificity of 0.79 (0.73 to 0.84), for identification of pre-diabetes, though different studies used different cut-off values.

24

Fasting plasma glucose had a mean sensitivity of 0.25 (0.19 to 0.32) and specificity of 0.94 (0.92 to 0.96). Different measures of glycaemic abnormality identified different subpopulations (for example, 47% : of people with abnormal HbA_1c had no other glycaemic abnormality). Lifestyle interventions were associated with a 36% (28% to 43%) reduction in relative risk of type 2 diabetes over six months to six years, attenuating to 20% (8% to 31%) at follow-up in the period after the trails.

CONCLUSIONS: HbA_1c is neither sensitive nor specific for detecting pre-diabetes; fasting glucose is specific but not sensitive. Interventions in people classified through screening as having pre-diabetes have some efficacy in preventing or delaying onset of type 2 diabetes in trial populations. As screening is inaccurate, many people will receives an incorrect diagnosis and be referred on for interventions while others will be falsely reassured and not offered the intervention. These findings suggest that "screen and treat" policies alone are unlikely to have substantial impact on the worsening epidemic of type 2 diabetes.

REGISTRATION: PROSPERO (No CRD42016042920). Bian RR, Piatt GA, Sen A, Plegue MA, De Michele ML, Hafez D, et al. The Effect of Technology-Mediated Diabetes Prevention Interventions on Weight: A Meta-Analysis. Journal of Medical Internet Research 2017;19(3):e76 BACKGROUND: Lifestyle interventions targeting weight loss, such as those delivered through the Diabetes

Prevention Program, reduce the risk of developing type 2 diabetes. Technology-mediated interventions may be an option to help overcome barriers to program delivery, and to disseminate diabetes prevention programs on a larger scale.

OBJECTIVE: We conducted a meta-analysis to evaluate the effect of such technology-mediated interventions on weight loss.

METHODS: In this meta-analysis, six databases were searched to identify studies reporting weight change that used technology to mediate diet and exercise interventions, and targeted individuals at high risk for developing type 2 diabetes. Studies published between January 1, 2002 and August 4, 2016 were included.

RESULTS: The search identified 1196 citations. Of those, 15 studies met the inclusion criteria and evaluated 18 technology-mediated intervention arms delivered to a total of 2774 participants. Study duration ranged from 12 weeks to 2 years. A random-effects meta-analysis showed a pooled weight loss effect of 3.76 kilograms (95% CI 2.8-4.7; P<.001) for the interventions. Several studies also reported improved glycemic control following the intervention. The small sample sizes and heterogeneity of the trials precluded an evaluation of which technology-mediated intervention method was most efficacious.

CONCLUSIONS: Technology-mediated diabetes prevention programs can result in clinically significant amounts of weight loss, as well as improvements in glycaemia in patients with prediabetes. Due to their potential for large-scale implementation, these interventions will play an important role in the dissemination of diabetes prevention programs.

Brown SA, Garcia AA, Zuniga JA,Lewis KA. Effectiveness of workplace diabetes prevention programs: A systematic review of the evidence. Patient Education & Counseling 2018;101(6):1036-1050 PURPOSE: The primary purpose is to review diabetes workplace interventions and the degree to which

they improve diabetes-related outcomes in employees diagnosed with or at risk for T2DM. METHODS: Three electronic databases and ancestry searches were used to identify peer reviewed articles

published in English from 2000 to June 2017. RESULTS: The number of participants represented by the 22 selected studies, excluding one large outlier, was

4243. On average, the samples were 57% female and ethnically diverse. Interventions-healthy eating behaviors, physical activity, and/or monitoring and self-managing diabetes and cardiovascular risk factors-were delivered in group sessions of fewer than 20 employees. Programs involved 1-h weekly sessions held during lunch hour or at other times during the workday for 12 to 24weeks. Study outcomes, commonly measured at 6 and/or 12 months, were consistently positive.

CONCLUSION: The literature search uncovered beginning evidence that workplace interventions hold promise for preventing diabetes and/or its complications. More rigorous, creatively designed, workplace studies, are needed for employees at high-risk for developing diabetes.

PRACTICE IMPLICATIONS: Implications include the need for employer education about the benefits of employer support for such programs and attention to motivational strategies so employees will take full advantage of programs that are offered.

Candido FG, Ton WT,Alfenas Rde C. Dairy products consumption versus type 2 diabetes prevention and treatment; a review of recent findings from human studies. Nutricion Hospitalaria 2013;28(5):1384-95 INTRODUCTION: It has been claimed that the appropriate consumption of dairy products can be beneficial

for the prevention and treatment of type 2 diabetes mellitus (T2DM). OBJECTIVE: The objective of this review is to critically analyze the main scientific evidence about this topic. METHODS: MEDLINE, PubMEd, Science Direct, SCIELO and LILACS were searched for studies published over

the past 12 years exploring the effects of the consumption of dairy products or its components (calcium, vitamin D and magnesium) on T2DM.

RESULTS AND DISCUSSION: Epidemiological studies indicate that consumption of at least three servings of low-

25

fat dairy products per day as a part of a healthy diet is crucial to reduce the risk of developing T2DM. The majority of the analyzed intervention studies reported beneficial effects of increased calcium and vitamin D ingestion on insulin sensitivity improvement and T2DM prevention.

CONCLUSIONS: Although the impact of dairy consumption to treat T2DM needs further investigation, the consumption of low-fat dairy products may be an important strategy to prevent and control T2DM.

Dimova ED, Mohan ARM, Swanson V,Evans JMM. Interventions for prevention of type 2 diabetes in relatives: A systematic review. Primary care diabetes 2017;11(4):313-326 The relatives and partners of people with type 2 diabetes are at increased risk of developing type 2

diabetes. This systematic review examines randomized controlled trials, written in English that tested an intervention, which aimed to modify behaviors known to delay or prevent type 2 diabetes, among the relatives or partners of people with type 2 diabetes. Study quality was assessed using the Cochrane Collaboration's tool for assessing risk of bias. Seven studies met the inclusion criteria. The majority of studies were at low risk of bias. Six studies tested an intervention in first-degree relatives of people with type 2 diabetes and one in partners. Intervention components and intervention intensity across studies varied, with those targeting diet and physical activity reporting the most significant changes in primary outcomes. Only one study did not observe significant changes in primary outcomes. There were three main recruitment approaches: advertising in the community, recruiting people through their relatives with diabetes, or identifying people as high risk by screening of their own health care contacts. Some evidence was found for potentially successful interventions to prevent type 2 diabetes among the relatives and partners of people with type 2 diabetes, although finding simple and effective methods to identify and recruit them remains a challenge. Future studies should explore the effect of patients' perceptions on their family members' behavior and capitalize on family relationships in order to increase intervention effectiveness.

Dunkley AJ, Bodicoat DH, Greaves CJ, Russell C, Yates T, Davies MJ, et al. Diabetes prevention in the real world: effectiveness of pragmatic lifestyle interventions for the prevention of type 2 diabetes and of the impact of adherence to guideline recommendations: a systematic review and meta-analysis. Diabetes Care 2014;37(4):922-33 OBJECTIVE To summarize the evidence on effectiveness of translational diabetes prevention programs,

based on promoting lifestyle change to prevent type 2 diabetes in real-world settings and to examine whether adherence to international guideline recommendations is associated with effectiveness. RESEARCH DESIGN AND METHODS Bibliographic databases were searched up to July 2012. Included studies had a follow-up of >=12 months and outcomes comparing change in body composition, glycemic control, or progression to diabetes. Lifestyle interventions aimed to translate evidence from previous efficacy trials of diabetes prevention into real-world intervention programs. Data were combined using random-effects meta-analysis and meta-regression considering the relationship between intervention effectiveness and adherence to guidelines. RESULTS Twenty-five studies met the inclusion criteria. The primary meta-analysis included 22 studies (24 study groups) with outcome data for weight loss at 12 months. The pooled result of the direct pairwise meta-analysis shows that lifestyle interventions resulted in a mean weight loss of 2.12 kg (95% CI -2.61 to -1.63; I(2) = 91.4%). Adherence to guidelines was significantly associated with a greater weight loss (an increase of 0.3 kg per point increase on a 12-point guideline-adherence scale). CONCLUSIONS Evidence suggests that pragmatic diabetes prevention programs are effective. Effectiveness varies substantially between programs but can be improved by maximizing guideline adherence. However, more research is needed to establish optimal strategies for maximizing both cost-effectiveness and longer-term maintenance of weight loss and diabetes prevention effects.

El Dib R, Gameiro OL, Ogata MS, Modolo NS, Braz LG, Jorge EC, et al. Zinc supplementation for the prevention of type 2 diabetes mellitus in adults with insulin resistance. Cochrane Database of Systematic Reviews 2015;5):CD005525 BACKGROUND: Diabetes is associated with long-term damage, dysfunction and failure of various organs,

especially the eyes, kidneys, nerves, heart and blood vessels. The risk of developing type 2 diabetes increases with age, obesity and lack of physical activity. Insulin resistance is a fundamental aspect of the aetiology of type 2 diabetes. Insulin resistance has been shown to be associated with atherosclerosis, dyslipidaemia, glucose intolerance, hyperuricaemia, hypertension and polycystic ovary syndrome. The mineral zinc plays a key role in the synthesis and action of insulin, both physiologically and in diabetes mellitus. Zinc seems to stimulate insulin action and insulin receptor tyrosine kinase activity.

OBJECTIVES: To assess the effects of zinc supplementation for the prevention of type 2 diabetes mellitus in adults with insulin resistance.

SEARCH METHODS: This review is an update of a previous Cochrane systematic review published in 2007. We searched the Cochrane Library (2015, Issue 3), MEDLINE, EMBASE, LILACS and the ICTRP trial register (from inception to March 2015). There were no language restrictions. We conducted citation searches and screened reference lists of included studies.

26

SELECTION CRITERIA: We included studies if they had a randomised or quasi-randomised design and if they investigated zinc supplementation compared with placebo or no intervention in adults with insulin resistance living in the community.

DATA COLLECTION AND ANALYSIS: Two review authors selected relevant trials, assessed risk of bias and extracted data.

MAIN RESULTS: We included three trials with a total of 128 participants in this review. The duration of zinc supplementation ranged between four and 12 weeks. Risk of bias was unclear for most studies regarding selection bias (random sequence generation, allocation concealment) and detection bias (blinding of outcome assessment). No study reported on our key outcome measures (incidence of type 2 diabetes mellitus, adverse events, health-related quality of life, all-cause mortality, diabetic complications, socioeconomic effects). Evaluation of insulin resistance as measured by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) showed neutral effects when comparing zinc supplementation with control (two trials; 114 participants). There were neutral effects for trials comparing zinc supplementation with placebo for total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol and triglycerides (2 studies, 70 participants). The one trial comparing zinc supplementation with exercise also showed neutral effects for total cholesterol, HDL and LDL cholesterol, and a mean difference in triglycerides of -30 mg/dL (95% confidence interval (CI) -49 to -10) in favour of zinc supplementation (53 participants). Various surrogate laboratory parameters were also analysed in the included trials.

AUTHORS' CONCLUSIONS: There is currently no evidence on which to base the use of zinc supplementation for the prevention of type 2 diabetes mellitus. Future trials should investigate patient-important outcome measures such as incidence of type 2 diabetes mellitus, health-related quality of life, diabetic complications, all-cause mortality and socioeconomic effects.

England CY, Andrews RC, Jago R,Thompson JL. A systematic review of brief dietary questionnaires suitable for clinical use in the prevention and management of obesity, cardiovascular disease and type 2 diabetes. European Journal of Clinical Nutrition 2015;69(9):977-1003 The aim of this systematic review was to identify and describe brief dietary assessment tools suitable for

use in clinical practice in the management of obesity, cardiovascular disease and type 2 diabetes. Papers describing development of brief (<35 items) dietary assessment questionnaires, that were accessible, simple to score and assessed aspects of the diet of relevance to the conditions of interest were identified from electronic databases. The development of 35 tools was described in 47 papers. Ten tools assessed healthy eating or healthy dietary patterns, 2 assessed adherence to the Mediterranean diet, 18 assessed dietary fat intake, and 5 assessed vegetable and/or fruit intake. Twenty tools were developed in North America. Test-retest reliability was conducted on 18 tools; correlation coefficients for total scores ranged from 0.59 to 0.95. Relative validation was conducted on 34 tools. The most common reference variable was percentage energy from fat (15 tools) and correlation coefficients ranged from 0.24, P<0.001 to 0.79, P<0.002. Tools that have been evaluated for reliability and/or relative validity are suitable for guiding clinicians when providing dietary advice. Variation in study design, settings and populations makes it difficult to recommend one tool over another, although future developers can enhance the understanding and use of tools by giving clear guidance as to the strengths and limitations of the study design. When selecting a tool, clinicians should consider whether their patient population is similar in characteristics to the evaluation sample.

Esposito K, Chiodini P, Maiorino MI, Bellastella G, Panagiotakos D,Giugliano D. Which diet for prevention of type 2 diabetes? A meta-analysis of prospective studies. Endocrine 2014;47(1):107-16 No specific diet is recommended to prevent type 2 diabetes. We did a meta-analysis of prospective cohort

studies to assess the association between different diets and prevention of type 2 diabetes. We did a comprehensive search of multiple electronic databases (Medline, Scopus, EMBASE, and ISI web of knowledge) until August 2013 using predefined criteria. We included prospective cohort studies that evaluated the role of different diets in type 2 diabetes prevention. Studies were selected by 2 independent reviewers. We did random-effects meta-analyses to determine the relative risk (RR) of incident diabetes associated with healthful dietary patterns. A total of 21,372 cases of incident diabetes, from 18 prospective studies, with 20 cohorts, in 4 world regions were identified. In the random-effect meta-analysis of the 20 cohorts, RR was 0.80 (95 % confidence interval (CI) = 0.74-0.86, P < 0.001), with high heterogeneity (I (2) = 57 %, P = 0.001) and no evidence of publication bias (Egger's test, P = 0.653). Exclusion of two cohorts produced identical RR (0.80, 95 % CI 0.76-0.84), with nonsignificant heterogeneity (I (2) = 9 %). The risk of incident diabetes did not appreciably change considering the geography (USA, Europe, and Asia), the duration of follow-up (<=10 and >10 years), and type of diets (Mediterranean and DASH, Dietary Approaches to Stop Hypertension, diets). There was a difference between at risk and general population (P = 0.0487), but the evidence was limited to two studies only. The results of our study demonstrate that several healthy diets are equally and consistently associated with a 20 % reduced risk of future type 2 diabetes.

27

Galaviz KI, Weber MB, Straus A, Haw JS, Narayan KMV,Ali MK. Global Diabetes Prevention Interventions: A Systematic Review and Network Meta-analysis of the Real-World Impact on Incidence, Weight, and Glucose. Diabetes Care 2018;41(7):1526-1534 OBJECTIVE: Understanding the real-world impacts of lifestyle modification (LSM) for diabetes prevention

is imperative to inform resource allocation. The purpose of this study was to synthetize global evidence on the impact of LSM strategies on diabetes incidence and risk factors in one parsimonious model.

RESEARCH DESIGN AND METHODS: PubMed, Embase, Cochrane Library, and ClinicalTrials.gov were searched for studies published between January 1990 and April 2015. Effectiveness/translation studies of any design testing LSM strategies, targeting high-risk populations (with prediabetes or diabetes risk factors), and reporting diabetes incidence, weight, or glucose outcomes were included. We extracted number of diabetes cases/incidence rates and mean changes in weight (kg), fasting blood glucose (FBG, mmol/L), 2-h postload glucose (mmol/L), and hemoglobin A_1c (%). Pairwise random-effects and frequentist random-effects network meta-analyses were used to obtain pooled effects.

RESULTS: Sixty-three studies were pooled in the meta-analysis (n = 17,272, mean age 49.7 years, 28.8% male, 60.8% white/European). In analyses restricted to controlled studies (n = 7), diabetes cumulative incidence was 9% among intervention participants and 12% among control participants (absolute risk reduction 3%; relative risk 0.71 [95% CI 0.58, 0.88]). In analyses combining controlled and uncontrolled studies (n = 14), participants receiving group education by health care professionals had 33% lower diabetes odds than control participants (odds ratio 0.67 [0.49, 0.92]). Intervention participants lost 1.5 kg more weight [-2.2, -0.8] and achieved a 0.09 mmol/L greater FBG decrease [-0.15, -0.03] than control participants. Every additional kilogram lost by participants was associated with 43% lower diabetes odds (beta = 0.57 [0.41, 0.78]).

CONCLUSIONS: Real-world LSM strategies can reduce diabetes risk, even with small weight reductions. Geng DF, Jin DM, Wu W, Liang YD,Wang JF. Angiotensin converting enzyme inhibitors for prevention of new-onset type 2 diabetes mellitus: a meta-analysis of 72,128 patients. International Journal of Cardiology 2013;167(6):2605-10 BACKGROUND: Angiotensin converting enzyme inhibitors (ACEIs) have been linked to reduced risk of

new-onset diabetes, but the evidence was insufficient. OBJECTIVE AND METHODS: The aim of this study was to evaluate the effect of ACEIs on the development of

new-onset type 2 diabetes. Randomized controlled trials (RCTs) about ACEIs and new-onset diabetes were identified by electronic and manual searches.

RESULTS: Nine RCTs with 92,404 patients (72,128 non-diabetic patients at baseline) were included in this study. Compared with control group, incidence of new-onset diabetes was significantly reduced in the ACEIs group [OR 0.80, (0.71, 0.91)], irrespective of achieved blood pressure levels at the follow-up. ACEIs therapy was associated with significant reduction in the risk of new-onset diabetes compared with beta-blockers/diuretics [OR 0.78, (0.65, 0.93)], placebo [OR 0.79, (0.64, 0.96)], or calcium channel blockers [OR 0.85, (0.73, 0.99)]. ACEIs treatment was associated with significant reduction in the risk of new-onset diabetes in patients with hypertension [OR 0.80, (0.68, 0.93)], coronary artery disease (CAD) or cardiovascular disease [OR 0.83, (0.68, 1.00)], or heart failure [OR 0.22, (0.10, 0.47)]. Among patients with impaired glucose tolerance or impaired fasting glucose, ramipril did not significantly reduce the incidence of diabetes [OR 0.91, (0.79, 1.05)], but significantly increased regression to normoglycemia.

CONCLUSION: ACEIs have beneficial effects in preventing new-onset diabetes. ACEIs provide additional benefits of lowering the risk of new-onset diabetes in patients with hypertension, CAD or other cardiovascular disease.

Glechner A, Harreiter J, Gartlehner G, Rohleder S, Kautzky A, Tuomilehto J, et al. Sex-specific differences in diabetes prevention: a systematic review and meta-analysis. Diabetologia 2015;58(2):242-54 AIMS/HYPOTHESIS: In people with prediabetes, lifestyle interventions and glucose-lowering medications

are effective in preventing the progression to type 2 diabetes. It is unclear whether differences in treatment effects between men and women need to be taken into consideration when choosing a preventive strategy for an individual person.

METHODS: We systematically searched PubMed, the Cochrane Library, EMBASE, CINAHL, Web of Science, and reference lists of pertinent review articles from 1980 to June 2013. We conducted random effects meta-analyses of published and unpublished data to determine differences of treatment effects between men and women.

RESULTS: Twelve randomised control trials (RCTs) provided sex-specific information on treatment effects. Compared with usual care, men and women who received lifestyle interventions had a lower rate of progression to type 2 diabetes (RR 0.60 [95% CI 0.35, 1.05] after 1 year; RR 0.63 [95% CI 0.51, 0.79] after 3 years); greater weight reduction (-2.45 kg; [95% CI -3.56, -1.33 kg] after 3 years); and greater reductions of fasting plasma glucose (-0.31 mmol/l [95% CI -0.48, -0.15] after 3 years) and 2 h post-challenge-glucose (-0.68 mmol/l [95% CI -1.03, -0.34] after 3 years). No statistically significant differences in treatment effects between men and women were apparent for any outcomes (p values of all comparisons >= 0.09).

CONCLUSIONS/INTERPRETATION: Our study emphasises the importance of preventive interventions in people

28

with prediabetes and indicates no differences of beneficial preventive effects on the incidence of type 2 diabetes and weight gain between men and women.

Hall DL, Lattie EG, McCalla JR,Saab PG. Translation of the Diabetes Prevention Program to Ethnic Communities in the United States. Journal of Immigrant & Minority Health 2016;18(2):479-89 The Diabetes Prevention Program (DPP), an evidenced-based lifestyle intervention for type 2 diabetes

(T2D), has been translated for use with ethnic minority communities throughout the United States that are disproportionately at-risk for T2D. The present paper sought to critically review ethnic translation studies of the DPP with respect to translation methods utilized, the success of these methods, and alternative or supplemental methodologies for future translation efforts. Manuscripts reviewed were found by searching PubMed and PsycINFO, using the terms: "diabetes prevention program" AND ["translation" or "ethnic"]. Of 89 papers found, only 6 described ethnic translations of the DPP in the United States, and were included in this review. Translations of the DPP to African American, Hispanic/Latino, Native Hawaiian and Other Pacific Islander, Arab American, and American Indian and Native Alaskan communities were identified and reviewed. The most common translation strategies included group-based delivery and use of bilingual study personnel. Generally, these factors appeared to increase acceptability of the intervention within the ethnic communities reviewed, and should be considered in future efforts to implement and translate the DPP to ethnic communities in the United States.

Haw JS, Galaviz KI, Straus AN, Kowalski AJ, Magee MJ, Weber MB, et al. Long-term Sustainability of Diabetes Prevention Approaches: A Systematic Review and Meta-analysis of Randomized Clinical Trials. JAMA Internal Medicine 2017;177(12):1808-1817 Importance: Diabetes prevention is imperative to slow worldwide growth of diabetes-related morbidity and

mortality. Yet the long-term efficacy of prevention strategies remains unknown. Objective: To estimate aggregate long-term effects of different diabetes prevention strategies on diabetes

incidence. Data Sources: Systematic searches of MEDLINE, EMBASE, Cochrane Library, and Web of Science databases.

The initial search was conducted on January 14, 2014, and was updated on February 20, 2015. Search terms included prediabetes, primary prevention, and risk reduction.

Study Selection: Eligible randomized clinical trials evaluated lifestyle modification (LSM) and medication interventions (>6 months) for diabetes prevention in adults (age >=18 years) at risk for diabetes, reporting between-group differences in diabetes incidence, published between January 1, 1990, and January 1, 2015. Studies testing alternative therapies and bariatric surgery, as well as those involving participants with gestational diabetes, type 1 or 2 diabetes, and metabolic syndrome, were excluded.

Data Extraction and Synthesis: Reviewers extracted the number of diabetes cases at the end of active intervention in treatment and control groups. Random-effects meta-analyses were used to obtain pooled relative risks (RRs), and reported incidence rates were used to compute pooled risk differences (RDs).

Main Outcomes and Measures: The main outcome was aggregate RRs of diabetes in treatment vs control participants. Treatment subtypes (ie, LSM components, medication classes) were stratified. To estimate sustainability, post-washout and follow-up RRs for medications and LSM interventions, respectively, were examined.

Results: Forty-three studies were included and pooled in meta-analysis (49029 participants; mean [SD] age, 57.3 [8.7] years; 48.0% [n=23549] men): 19 tested medications; 19 evaluated LSM, and 5 tested combined medications and LSM. At the end of the active intervention (range, 0.5-6.3 years), LSM was associated with an RR reduction of 39% (RR, 0.61; 95% CI, 0.54-0.68), and medications were associated with an RR reduction of 36% (RR, 0.64; 95% CI, 0.54-0.76). The observed RD for LSM and medication studies was 4.0 (95% CI, 1.8-6.3) cases per 100 person-years or a number-needed-to-treat of 25. At the end of the washout or follow-up periods, LSM studies (mean follow-up, 7.2 years; range, 5.7-9.4 years) achieved an RR reduction of 28% (RR, 0.72; 95% CI, 0.60-0.86); medication studies (mean follow-up, 17 weeks; range, 2-52 weeks) showed no sustained RR reduction (RR, 0.95; 95% CI, 0.79-1.14).

Conclusions and Relevance: In adults at risk for diabetes, LSM and medications (weight loss and insulin-sensitizing agents) successfully reduced diabetes incidence. Medication effects were short lived. The LSM interventions were sustained for several years; however, their effects declined with time, suggesting that interventions to preserve effects are needed.

He S, Yu S, Zhou Z, Wang C, Wu Y,Li W. Effect of vitamin D supplementation on fasting plasma glucose, insulin resistance and prevention of type 2 diabetes mellitus in non-diabetics: A systematic review and meta-analysis. Biomedical Reports 2018;8(5):475-484 Increasing epidemiological studies suggest that there is an association between vitamin D deficiency and

risk of type 2 diabetes mellitus (T2DM). Therefore, randomized clinical trials (RCTs) have been performed to observe the effect of vitamin D supplementation on preventing T2DM, decreasing fasting plasma glucose (FPG) and improving insulin resistance to confirm the association between vitamin D and T2DM. However, the results of RCTs on controlling FPG level, improving insulin resistance and preventing T2DM in non-diabetics are inconsistent. In the present study, a systematic meta-analysis considering individual

29

variation and intervention strategy was conducted to establish an objective and definitive conclusion. The results suggested that vitamin D supplementation had no significant effect on controlling FPG level, improving insulin resistance or preventing T2DM in non-diabetics in a pooled meta-analysis of 23 articles (containing 28 RCTs). However, stratified analysis indicated that supplementation of vitamin D had differential effects on FPG control, insulin sensitivity improvement and T2DM prevention in individuals with different baseline states: FPG was decreased for those with BMI <25 (P=0.048) or 20<= 25(OH)D <30 ng/ml (P=0.002); insulin resistance was improved for those with 25(OH)D >=30 ng/ml (P=0.021); and risk of T2DM was lower for pre-diabetic individuals (P=0.047) or for those with 25<= BMI <30 (P=0.032). Additionally, the effect on T2DM prevention was improved when the supplement dose was >2,000 IU/day (P=0.047) and with intervention without calcium (P=0.047). Thus, further trials should focus on individual baselines and the supplementation strategy of vitamin D in the prevention of T2DM. Copyright © 2018, Spandidos Publications. All rights reserved.

Hemmingsen B, Sonne DP, Metzendorf MI,Richter B. Insulin secretagogues for prevention or delay of type 2 diabetes mellitus and its associated complications in persons at increased risk for the development of type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2016;10(CD012151 BACKGROUND: The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into

a substantial health problem worldwide. Whether insulin secretagogues (sulphonylureas and meglitinide analogues) are able to prevent or delay T2DM and its associated complications in people at risk for the development of T2DM is unknown.

OBJECTIVES: To assess the effects of insulin secretagogues on the prevention or delay of T2DM and its associated complications in people with impaired glucose tolerance, impaired fasting blood glucose, moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these.

SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, PubMed, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and the reference lists of systematic reviews, articles and health technology assessment reports. We asked investigators of the included trials for information about additional trials. The date of the last search of all databases was April 2016.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) with a duration of 12 weeks or more comparing insulin secretagogues with any pharmacological glucose-lowering intervention, behaviour-changing intervention, placebo or no intervention in people with impaired fasting glucose, impaired glucose tolerance, moderately elevated HbA1c or combinations of these.

DATA COLLECTION AND ANALYSIS: Two review authors read all abstracts and full-text articles/records, assessed quality and extracted outcome data independently. One review author extracted data which were checked by a second review author. We resolved discrepancies by consensus or the involvement of a third review author. For meta-analyses we used a random-effects model with investigation of risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We carried out trial sequential analyses (TSAs) for all outcomes that could be meta-analysed. We assessed the overall quality of the evidence by using the GRADE instrument.

MAIN RESULTS: We included six RCTs with 10,018 participants; 4791 participants with data on allocation to intervention groups were randomised to a second- or third-generation sulphonylurea or a meglitinide analogue as monotherapy and 29 participants were randomised to a second-generation sulphonylurea plus metformin. Three trials investigated a second-generation sulphonylurea, two trials investigated a third-generation sulphonylurea and one trial a meglitinide analogue. A total of 4873 participants with data on allocation to control groups were randomised to a comparator group; 4820 participants were randomised to placebo, 23 to diet and exercise, and 30 participants to metformin monotherapy. One RCT of nateglinide contributed 95% of all participants. The duration of the intervention varied from six months to five years. We judged none of the included trials as at low risk of bias for all 'Risk of bias' domains.All-cause and cardiovascular mortality following sulphonylurea (glimepiride) treatment were rarely observed (very low-quality evidence). The RR for incidence of T2DM comparing glimepiride monotherapy with placebo was 0.75; 95% CI 0.54 to 1.04; P = 0.08; 2 trials; 307 participants; very low-quality evidence. One of the trials reporting on the incidence of T2DM did not define the diagnostic criteria used. The other trial diagnosed T2DM as two consecutive fasting blood glucose values >= 6.1 mmol/L. TSA showed that only 4.5% of the diversity-adjusted required information size was accrued so far. No trial reported data on serious adverse events, non-fatal myocardial infarction (MI), non-fatal stroke, congestive heart failure (HF), health-related quality of life or socioeconomic effects.One trial with a follow-up of five years compared a meglitinide analogue (nateglinide) with placebo. A total of 310/4645 (6.7%) participants allocated to nateglinide died compared with 312/4661 (6.7%) participants allocated to placebo (hazard ratio (HR) 1.00; 95% CI 0.85 to 1.17; P = 0.98; moderate-quality evidence). The two main criteria for diagnosing T2DM were a fasting plasma glucose level >= 7.0 mmol/L or a 2-hour post challenge glucose >= 11.1 mmol/L. T2DM developed in 1674/4645 (36.0%) participants in the nateglinide group and in 1580/4661 (33.9%) in the placebo group (HR 1.07; 95% CI 1.00 to 1.15; P = 0.05; moderate-quality evidence). One or more serious adverse event was reported in 2066/4602 (44.9%) participants allocated to nateglinide compared with 2089/4599 (45.6%) participants allocated to placebo. A total of 126/4645 (2.7%) participants allocated to nateglinide died

30

because of cardiovascular disease compared with 118/4661 (2.5%) participants allocated to placebo (HR 1.07; 95% CI 0.83 to 1.38; P = 0.60; moderate-quality evidence). Comparing participants receiving nateglinide with those receiving placebo for the outcomes MI, non-fatal stroke and HF gave the following event rates: MI 116/4645 (2.5%) versus 122/4661 (2.6%), stroke 100/4645 (2.2%) versus 110/4661 (2.4%) and numbers hospitalised for HF 85/4645 (1.8%) versus 100/4661 (2.1%) - (HR 0.85; 95% CI 0.64 to 1.14; P = 0.27). The quality of the evidence was moderate for all these outcomes. Health-related quality of life or socioeconomic effects were not reported.

AUTHORS' CONCLUSIONS: There is insufficient evidence to demonstrate whether insulin secretagogues compared mainly with placebo reduce the risk of developing T2DM and its associated complications in people at increased risk for the development of T2DM. Most trials did not investigate patient-important outcomes.

Hemmingsen B, Sonne DP, Metzendorf MI,Richter B. Dipeptidyl-peptidase (DPP)-4 inhibitors and glucagon-like peptide (GLP)-1 analogues for prevention or delay of type 2 diabetes mellitus and its associated complications in people at increased risk for the development of type 2 diabetes mellitus. Cochrane Database of Systematic Reviews 2017;5(CD012204 BACKGROUND: The projected rise in the incidence of type 2 diabetes mellitus (T2DM) could develop into

a substantial health problem worldwide. Whether dipeptidyl-peptidase (DPP)-4 inhibitors or glucagon-like peptide (GLP)-1 analogues are able to prevent or delay T2DM and its associated complications in people at risk for the development of T2DM is unknown.

OBJECTIVES: To assess the effects of DPP-4 inhibitors and GLP-1 analogues on the prevention or delay of T2DM and its associated complications in people with impaired glucose tolerance, impaired fasting blood glucose, moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these.

SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials; MEDLINE; PubMed; Embase; ClinicalTrials.gov; the World Health Organization (WHO) International Clinical Trials Registry Platform; and the reference lists of systematic reviews, articles and health technology assessment reports. We asked investigators of the included trials for information about additional trials. The date of the last search of all databases was January 2017.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) with a duration of 12 weeks or more comparing DPP-4 inhibitors and GLP-1 analogues with any pharmacological glucose-lowering intervention, behaviour-changing intervention, placebo or no intervention in people with impaired fasting glucose, impaired glucose tolerance, moderately elevated HbA1c or combinations of these.

DATA COLLECTION AND ANALYSIS: Two review authors read all abstracts and full-text articles and records, assessed quality and extracted outcome data independently. One review author extracted data which were checked by a second review author. We resolved discrepancies by consensus or the involvement of a third review author. For meta-analyses, we planned to use a random-effects model with investigation of risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the overall quality of the evidence using the GRADE instrument.

MAIN RESULTS: We included seven completed RCTs; about 98 participants were randomised to a DPP-4 inhibitor as monotherapy and 1620 participants were randomised to a GLP-1 analogue as monotherapy. Two trials investigated a DPP-4 inhibitor and five trials investigated a GLP-1 analogue. A total of 924 participants with data on allocation to control groups were randomised to a comparator group; 889 participants were randomised to placebo and 33 participants to metformin monotherapy. One RCT of liraglutide contributed 85% of all participants. The duration of the intervention varied from 12 weeks to 160 weeks. We judged none of the included trials at low risk of bias for all 'Risk of bias' domains and did not perform meta-analyses because there were not enough trials.One trial comparing the DPP-4 inhibitor vildagliptin with placebo reported no deaths (very low-quality evidence). The incidence of T2DM by means of WHO diagnostic criteria in this trial was 3/90 participants randomised to vildagliptin versus 1/89 participants randomised to placebo (very low-quality evidence). Also, 1/90 participants on vildagliptin versus 2/89 participants on placebo experienced a serious adverse event (very low-quality evidence). One out of 90 participants experienced congestive heart failure in the vildagliptin group versus none in the placebo group (very low-quality evidence). There were no data on non-fatal myocardial infarction, stroke, health-related quality of life or socioeconomic effects reported.All-cause and cardiovascular mortality following treatment with GLP-1 analogues were rarely reported; one trial of exenatide reported that no participant died. Another trial of liraglutide 3.0 mg showed that 2/1501 in the liraglutide group versus 2/747 in the placebo group died after 160 weeks of treatment (very low-quality evidence).The incidence of T2DM following treatment with liraglutide 3.0 mg compared to placebo after 160 weeks was 26/1472 (1.8%) participants randomised to liraglutide versus 46/738 (6.2%) participants randomised to placebo (very low-quality evidence). The trial established the risk for (diagnosis of) T2DM as HbA1c 5.7% to 6.4% (6.5% or greater), fasting plasma glucose 5.6 mmol/L or greater to 6.9 mmol/L or less (7.0 mmol/L or greater) or two-hour post-load plasma glucose 7.8 mmol/L or greater to 11.0 mmol/L (11.1 mmol/L). Altogether, 70/1472 (66%) participants regressed from intermediate hyperglycaemia to normoglycaemia compared with 268/738 (36%) participants in the placebo group. The incidence of T2DM after the 12-week off-treatment extension period

31

(i.e. after 172 weeks) showed that five additional participants were diagnosed T2DM in the liraglutide group, compared with one participant in the placebo group. After 12-week treatment cessation, 740/1472 (50%) participants in the liraglutide group compared with 263/738 (36%) participants in the placebo group had normoglycaemia.One trial used exenatide and 2/17 participants randomised to exenatide versus 1/16 participants randomised to placebo developed T2DM (very low-quality evidence). This trial did not provide a definition of T2DM. One trial reported serious adverse events in 230/1524 (15.1%) participants in the liraglutide 3.0 mg arm versus 96/755 (12.7%) participants in the placebo arm (very low quality evidence). There were no serious adverse events in the trial using exenatide. Non-fatal myocardial infarction was reported in 1/1524 participants in the liraglutide arm and in 0/55 participants in the placebo arm at 172 weeks (very low-quality evidence). One trial reported congestive heart failure in 1/1524 participants in the liraglutide arm and in 1/755 participants in the placebo arm (very low-quality evidence). Participants receiving liraglutide compared with placebo had a small mean improvement in the physical component of the 36-item Short Form scale showing a difference of 0.87 points (95% CI 0.17 to 1.58; P = 0.02; 1 trial; 1791 participants; very low-quality evidence). No trial evaluating GLP-1-analogues reported data on stroke, microvascular complications

AUTHORS' CONCLUSIONS: There is no firm evidence that DPP-4 inhibitors or GLP-1 analogues compared mainly with placebo substantially influence the risk of T2DM and especially its associated complications in people at increased risk for the development of T2DM. Most trials did not investigate patient-important outcomes.

Howells L, Musaddaq B, McKay AJ,Majeed A. Clinical impact of lifestyle interventions for the prevention of diabetes: an overview of systematic reviews. BMJ Open 2016;6(12):e013806 OBJECTIVES: To review the clinical outcomes of combined diet and physical activity interventions for

populations at high risk of type 2 diabetes. DESIGN: Overview of systematic reviews (search dates April-December 2015). SETTING: Any level of care; no geographical restriction. PARTICIPANTS: Adults at high risk of diabetes (as per measures of glycaemia, risk assessment or presence of

risk factors). INTERVENTIONS: Combined diet and physical activity interventions including >=2 interactions with a healthcare

professional, and >=12 months follow-up. OUTCOME MEASURES: Primary: glycaemia, diabetes incidence. Secondary: behaviour change, measures of

adiposity, vascular disease and mortality. RESULTS: 19 recent reviews were identified for inclusion; 5 with AMSTAR scores <8. Most considered only

randomised controlled trials (RCTs), and RCTs were the major data source in the remainder. Five trials were included in most reviews. Almost all analyses reported that interventions were associated with net reductions in diabetes incidence, measures of glycaemia and adiposity, at follow-up durations of up to 23 years (typically <6). Small effect sizes and potentially transient effect were reported in some studies, and some reviewers noted that durability of intervention impact was potentially sensitive to duration of intervention and adherence to behaviour change. Behaviour change, vascular disease and mortality outcome data were infrequently reported, and evidence of the impact of intervention on these outcomes was minimal. Evidence for age effect was mixed, and sex and ethnicity effect were little considered.

CONCLUSIONS: Relatively long-duration lifestyle interventions can limit or delay progression to diabetes under trial conditions. However, outcomes from more time-limited interventions, and those applied in routine clinical settings, appear more variable, in keeping with the findings of recent pragmatic trials. There is little evidence of intervention impact on vascular outcomes or mortality end points in any context. 'Real-world' implementation of lifestyle interventions for diabetes prevention may be expected to lead to modest outcomes.

Johnson M, Jones R, Freeman C, Woods HB, Gillett M, Goyder E, et al. Can diabetes prevention programmes be translated effectively into real-world settings and still deliver improved outcomes? A synthesis of evidence. Diabetic Medicine 2013;30(1):3-15 OBJECTIVE: Randomized trials provide evidence that intensive lifestyle interventions leading to dietary

and physical activity change can delay or prevent Type 2 diabetes. Translational studies have assessed the impact of interventions based on, but less intensive than, trial protocols delivered in community settings with high-risk populations. The aim of this review was to synthesize evidence from translational studies of any design to assess the impact of interventions delivered outside large randomized trials.

METHODS: Medical and scientific databases were searched using specified inclusion and exclusion criteria. Studies were included that used a tested diabetes preventive study protocol with an adult population at risk from Type 2 diabetes. Included papers were quality assessed and data extracted using recommended methods.

RESULTS: From an initial 793 papers, 19 papers reporting 17 studies were included. Translational studies from a range of settings utilized a variety of methods. All were based on the US Diabetes Prevention Programme protocol or the Finnish Diabetes Prevention Study, with modifications that increased feasibility and access. The main outcome that was reported in all studies was weight change. Weight loss, which occurred in all

32

but one study, was greater in intervention arms than in control subjects. No consistent differences were found in blood glucose or waist circumference.

CONCLUSIONS: Translational studies based on the intensive diabetes prevention programmes showed that there is potential for less intensive interventions both to be feasible and to have an impact on future progression to diabetes in at-risk individuals.

Khemayanto H,Shi B. Role of Mediterranean diet in prevention and management of type 2 diabetes. Chinese Medical Journal 2014;127(20):3651-6 OBJECTIVE: To summarize the importance of Mediterranean diet in the prevention and management of

type 2 diabetes. DATA SOURCES: We searched electronic database on PubMed up to 14 April 2014, we identified these articles

with following key words: "Mediterranean diet" and "diabetes". The initial search resulted in 451 entries. The search strategy had no language and publication date restrictions. The relevance of the studies was assessed based only on the title and abstract. The studies included in our review had to match the following inclusion criteria: (1) randomized clinical trials and meta-analysis or systematic review, and (2) provided strong evidence for the diet as a way to prevent type 2 diabetes, and improve glycemic control and cardiovascular risk factors in diabetic patients. We reviewed 49 manuscripts and only 22 met our inclusion criteria.

STUDY SELECTION: Relevant literatures including randomized control trials, meta-analysis or systematic review. RESULTS: Based on several studies, Mediterranean diet is inversely related to type 2 diabetes and plays important

roles in the management of type 2 diabetes. Based on the evidence gathered and evaluated from various studies, we concluded combination and interaction of Mediterranean diet components, such as fruits, vegetables, nuts, legumes, whole grains, fish and moderate intakes of red wine, which contain essential nutrients and health promoting properties, including high fibers, high magnesium, high anti-oxidant and high monounsaturatal fatty acids (MUFA). Interaction and combination of these essential nutrients and health promoting properties found to lower body weight, hemoglobin A1C (HbA1c), low density lipoprotein (LDL), oxidative-stress and improve high density lipoprotein (HDL) level; which are beneficial for prevention and prognosis improvement of type 2 diabetes.

CONCLUSIONS: In the modern society, poor dietary habits accompanied by inadequate physical activity are associated with the risk of having obesity and type 2 diabetes. Promoting healthy lifestyle and diet are not only beneficial in the prevention and treatment of various diseases but also important in maintaining the overall health. Switching from unhealthy diet to health-friendly diet such as Mediterranean diet represents healthy lifestyle choice.

Lindstrom J, Wikstrom K, Maggini M, Icks A, Kuske S, Rothe U, et al. Quality indicators for diabetes prevention programs in health care targeted at people at high risk. Annali Dell'Istituto Superiore di Sanita 2015;51(3):187-91 OBJECTIVE: Type 2 diabetes can be efficiently prevented by lifestyle intervention provided for people at

high diabetes risk. The aim of this paper was to conduct a literature search on existing quality indicators for type 2 diabetes prevention and to collate and present a set of indicators that could be applied in European countries with different health care systems and cultures.

METHODS: Scientific and grey literature was searched for relevant studies using electronic databases. We also hand searched previous systematic reviews and reference lists of relevant articles.

RESULTS: The only publication identified was the report presenting the results from the IMAGE project. The IMAGE indicators were used as the basis for the proposed indicators.

CONCLUSIONS: Publications on quality indicators of diabetes prevention programmes are scarce. The quality indicators presented here are a first step toward the definition of a core set of European indicators to monitor and improve the quality of diabetes prevention.

McCurley JL, Crawford MA,Gallo LC. Prevention of Type 2 Diabetes in U.S. Hispanic Youth: A Systematic Review of Lifestyle Interventions. American Journal of Preventive Medicine 2017;53(4):519-532 CONTEXT: Prevalence of type 2 diabetes mellitus (T2DM) in youth has increased rapidly in recent

decades along with rises in childhood obesity. Disparities in risk and prevalence of T2DM are evident in Hispanic youth when compared with non-Hispanic whites. Targeted diabetes prevention programs have been recommended to reduce risk prior to adulthood in this population. This systematic review explores the effectiveness of lifestyle-based diabetes prevention interventions for Hispanic youth.

EVIDENCE ACQUISITION: PubMed, PsycINFO, Web of Science, and CENTRAL were searched from database inception to March 1, 2017, for studies that evaluated lifestyle-focused prevention trials targeting U.S. Hispanic youth under age 18 years. Fifteen publications met criteria for inclusion.

EVIDENCE SYNTHESIS: Of the 15 studies, 11 were RCTs; four were uncontrolled. Interventions were heterogeneous in intensity, content, and setting. Duration of most trials was 12-16 weeks. Mean age of participants ranged from 9.8 to 15.8 years, sample sizes were generally small, and the majority of participants were overweight (BMI >=85th percentile). Three studies reported statistically significant reductions in mean BMI, four in BMI z-score, and six in fasting glucose/insulin. Study quality was moderate to high. Effect sizes were generally small to medium.

33

CONCLUSIONS: Evidence for the impact of lifestyle-based diabetes prevention interventions targeting U.S. Hispanic youth remains limited. Few interventions demonstrated success in reducing BMI and glucose regulation and follow-up times were brief. More studies are needed that recruit larger samples sizes, extend follow-up times, explore innovative delivery modalities, and examine effectiveness across sex and age.

McCurley JL, Gutierrez AP,Gallo LC. Diabetes Prevention in U.S. Hispanic Adults: A Systematic Review of Culturally Tailored Interventions. American Journal of Preventive Medicine 2017;52(4):519-529 CONTEXT: Type 2 diabetes, prediabetes, and metabolic syndrome are highly prevalent in Hispanic

individuals in the U.S. Cultural adaptations of traditional lifestyle interventions have been recommended to better reach this high-risk population. This systematic review examined the effectiveness of diabetes prevention programs for Hispanics in lowering risk for Type 2 diabetes, as evidenced by a reduction in weight or improvement in glucose regulation.

EVIDENCE ACQUISITION: PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Web of Science, and PsycINFO were searched from database inception to June 2016 for studies that evaluated diabetes prevention trials targeting U.S. Hispanic populations. Twelve publications met criteria for inclusion.

EVIDENCE SYNTHESIS: Interventions varied substantially in length, rigor, and tailoring strategies. Five of 12 studies were RCTs. Eight studies included entirely or largely (>70%) female samples. All studies were delivered in Spanish and took place in community settings. Nine studies reported significant reductions in weight, and two in glucose regulation, post-intervention or when compared with controls. Effect sizes were small to moderate, study quality was moderate, and attrition was high in most trials. Interventions with the largest effect sizes included one or more of the following adaptations: literacy modification, Hispanic foods/recipes, cultural diabetes beliefs, family/friend participation, structured community input, and innovative experiential learning.

CONCLUSIONS: Culturally tailored lifestyle interventions for diabetes prevention appear to be modestly effective in reducing risk for diabetes in Hispanics in the U.S. More studies are needed that utilize randomized controlled designs, recruit Hispanic men, report intervention content and tailoring strategies systematically, and publish participant evaluation and feedback.

Merlotti C, Morabito A, Ceriani V,Pontiroli AE. Prevention of type 2 diabetes in obese at-risk subjects: a systematic review and meta-analysis. Acta Diabetologica 2014;51(5):853-63 Different intervention strategies can prevent new cases of type 2 diabetes (T2DM) in obese subjects. The

present systematic review and meta-analysis evaluates the effectiveness of different strategies in prevention of type 2 diabetes in obese subjects. Studies were grouped into five different strategies: (1) physical activity +/- diet; (2) anti-diabetic drugs (glitazones, metformin, glinides, alfa-glucosidase inhibitors); (3) antihypertensive drugs (ACE inhibitors, ARB); (4) weight loss-promoting drugs and lipid-lowering drugs (orlistat, bezafibrate, phentermine/topiramate controlled release); and (5) bariatric surgery. Only controlled studies, dealing with subjects BMI >= 30 kg/m(2), were included in the analysis, whether randomized or non-randomized studies. Appropriate methodology (PRISMA statement) was adhered to. Publication bias was formally assessed. Eighteen studies (43,669 subjects, 30,774 with impaired glucose tolerance and/or impaired fasting glucose), published in English language as full papers, were analyzed to identify predictors of new cases of T2DM and were included in a meta-analysis (random-effects model) to study the effect of different strategies. Intervention effect (new cases of diabetes) was expressed as odds ratio (OR), with 95 % confidence intervals (CIs). In obese subjects, non-surgical strategies were able to prevent T2DM, with different effectiveness [OR from 0.44 (0.36-0.52) to 0.86 (0.80-0.92)]; in morbidly obese subjects, bariatric surgery was highly effective [OR = 0.10 (0.02-0.49)]. At meta-regression analysis, factors associated with effectiveness were weight loss, young age and fasting insulin levels. Publication bias was present only when considering all studies together. These data indicate that several strategies, with different effectiveness, can prevent T2DM in obese subjects.

Merlotti C, Morabito A,Pontiroli AE. Prevention of type 2 diabetes; a systematic review and meta-analysis of different intervention strategies. Diabetes, Obesity & Metabolism 2014;16(8):719-27 AIM: Different intervention strategies can prevent type 2 diabetes (T2DM). Aim of the present systematic

review and meta-analysis was to evaluate the effectiveness of different strategies. METHODS: Studies were grouped into 15 different strategies: 1: diet plus physical activity; 2: physical activity; 3-6:

anti-diabetic drugs [glitazones, metformin, beta-cell stimulating drugs (sulphanylureas, glinides), alfa-glucosidase inhibitors]; 7-8: cardiovascular drugs (ACE inhibitors, ARB, calcium antagonists); 9-14 [diets, lipid-affecting drugs (orlistat, bezafibrate), vitamins, micronutrients, estrogens, alcohol, coffee]; 15: bariatric surgery. Only controlled studies were included in the analysis, whether randomized, non-randomized, observational studies, whether primarily designed to assess incident cases of diabetes, or performed with other purposes, such as control of hypertension, of ischemic heart disease or prevention of cardiovascular events. Appropriate methodology [preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement] was used. Seventy-one studies (490813 subjects), published as full papers, were analysed to identify predictors of new cases of T2DM, and were included in a meta-analysis (random-

34

effects model) to study the effect of different strategies. Intervention effect (new cases of diabetes) was expressed as odds ratio (OR), with 95% confidence intervals (C.I.s). Publication bias was formally assessed.

RESULTS: Body mass index was in the overweight range for 13 groups, obese or morbidly obese in lipid-affecting drugs and in bariatric surgery. Non-surgical strategies, except for beta-cell stimulating drugs, estrogens and vitamins, were able to prevent T2DM, with different effectiveness, from 0.37 (C.I. 0.26-0.52) to 0.85 (C.I. 0.77-0.93); the most effective strategy was bariatric surgery in morbidly obese subjects [0.16 (C.I. 0.11,0.24)]. At meta-regression analysis, age of subjects and amount of weight lost were associated with effectiveness of intervention.

CONCLUSIONS: These data indicate that several strategies prevent T2DM, making it possible to make a choice for the individual subject.

Merone L,McDermott R. Nutritional anti-inflammatories in the treatment and prevention of type 2 diabetes mellitus and the metabolic syndrome. Diabetes Research & Clinical Practice 2017;127(238-253 AIMS: Obesity-fuelled metabolic syndrome and diabetes is now a global epidemic. There is increasing

evidence that these and other chronic conditions have common inflammatory antecedents. There is an interest in nutritionally based anti-inflammatory treatments for type 2 diabetes and metabolic syndrome. The aim of this review is to examine the evidence from a 5-year period; 2011-2016, for nutritionally based anti-inflammatory treatments for the Metabolic Syndrome and Type 2 Diabetes Mellitus.

METHODS: A literature search produced a total number of 1377 records, of which 26 papers were evaluated. RESULTS: Literature was analysed and tabulated according to date, outcome measures and results. CONCLUSION: The evidence is strong for use of polyphenolic compounds, fish oils and vitamins in reducing

inflammation biomarkers, however the impact on metabolic control is less evident. Messina J, Campbell S, Morris R, Eyles E,Sanders C. A narrative systematic review of factors affecting diabetes prevention in primary care settings. PLoS ONE [Electronic Resource] 2017;12(5):e0177699 BACKGROUND: Type 2 diabetes is impacting millions of people globally; however, many future cases can

be prevented through lifestyle changes and interventions. Primary care is an important setting for diabetes prevention, for at-risk populations, because it is a patient's primary point of contact with the health care system and professionals can provide lifestyle counselling and support, as well as monitoring health outcomes. These are all essential elements for diabetes prevention for at-risk adults.

AIM: To understand the factors related to the delivery and uptake of type 2 diabetes prevention interventions within primary care in higher income countries.

METHODS: For this narrative systematic review, we combined qualitative and quantitative studies of diabetes prevention within a primary care setting for patients at-risk of developing the condition. We used an iterative approach for evidence collection, which included using several databases (MEDLINE, Embase, Pysch info, BNI, SSCI, CINAHL, ASSIA), where we combined diabetes terms with primary care terms. Narrative and thematic synthesis were utilised to identify the prominent themes emerging from the data.

RESULTS: A database of 6646 records was screened by the research team, and 18 papers were included. Three major themes were identified in this review. The first theme of context and setting of diabetes progression includes the risk and progression of diabetes, primary care as a setting, and where the responsibility for change is thought to lie. This review also found mixed views on the value of preventative services within primary care. The second theme focused on the various patient factors associated with diabetes prevention such as a patient's motivation to modify their current lifestyle, perceptions and knowledge (or lack thereof) of the impacts of diabetes, lack of follow-up in healthcare settings, and trust in healthcare professionals. The third theme was centred on professional factors impacting on diabetes prevention which included workload, time constraints, resources, self-efficacy and knowledge as well as professionals' perception of patient motivations towards change.

CONCLUSION: This review explored the factors influencing diabetes prevention in primary care, and identified the context of prevention, as well as patient and professional factors related to preventative services being offered in primary care. This systematic review complements previous reviews of real-world settings by exploring the significant factors in prevention, and the findings are relevant to academics, policymakers, patients and practitioners interested in understanding the factors associated with the delivery and uptake of diabetes prevention interventions.

Mudaliar U, Zabetian A, Goodman M, Echouffo-Tcheugui JB, Albright AL, Gregg EW, et al. Cardiometabolic Risk Factor Changes Observed in Diabetes Prevention Programs in US Settings: A Systematic Review and Meta-analysis. PLoS Medicine / Public Library of Science 2016;13(7):e1002095 BACKGROUND: The Diabetes Prevention Program (DPP) study showed that weight loss in high-risk

adults lowered diabetes incidence and cardiovascular disease risk. No prior analyses have aggregated weight and cardiometabolic risk factor changes observed in studies implementing DPP interventions in nonresearch settings in the United States.

METHODS AND FINDINGS: In this systematic review and meta-analysis, we pooled data from studies in the United States implementing DPP lifestyle modification programs (focused on modest [5%-7%] weight loss

35

through >=150 min of moderate physical activity per week and restriction of fat intake) in clinical, community, and online settings. We reported aggregated pre- and post-intervention weight and cardiometabolic risk factor changes (fasting blood glucose [FBG], glycosylated hemoglobin [HbA1c], systolic or diastolic blood pressure [SBP/DBP], total [TC] or HDL-cholesterol). We searched the MEDLINE, EMBASE, Cochrane Library, and Clinicaltrials.gov databases from January 1, 2003, to May 1, 2016. Two reviewers independently evaluated article eligibility and extracted data on study designs, populations enrolled, intervention program characteristics (duration, number of core and maintenance sessions), and outcomes. We used a random effects model to calculate summary estimates for each outcome and associated 95% confidence intervals (CI). To examine sources of heterogeneity, results were stratified according to the presence of maintenance sessions, risk level of participants (prediabetes or other), and intervention delivery personnel (lay or professional). Forty-four studies that enrolled 8,995 participants met eligibility criteria. Participants had an average age of 50.8 years and body mass index (BMI) of 34.8 kg/m2, and 25.2% were male. On average, study follow-up was 9.3 mo (median 12.0) with a range of 1.5 to 36 months; programs offered a mean of 12.6 sessions, with mean participant attendance of 11.0 core sessions. Sixty percent of programs offered some form of post-core maintenance (either email or in person). Mean absolute changes observed were: weight -3.77 kg (95% CI: -4.55; -2.99), HbA1c -0.21% (-0.29; -0.13), FBG -2.40 mg/dL (-3.59; -1.21), SBP -4.29 mmHg (-5.73, -2.84), DBP -2.56 mmHg (-3.40, 1.71), HDL +0.85 mg/dL (-0.10, 1.60), and TC -5.34 mg/dL (-9.72, -0.97). Programs with a maintenance component achieved greater reductions in weight (additional -1.66kg) and FBG (additional -3.14 mg/dl). Findings are subject to incomplete reporting and heterogeneity of studies included, and confounding because most included studies used pre-post study designs.

CONCLUSIONS: DPP lifestyle modification programs achieved clinically meaningful weight and cardiometabolic health improvements. Together, these data suggest that additional value is gained from these programs, reinforcing that they are likely very cost-effective.

Muley A, Muley P,Shah M. ALA, fatty fish or marine n-3 fatty acids for preventing DM?: a systematic review and meta-analysis. Current Diabetes Reviews 2014;10(3):158-65 Diabetes mellitus (T2DM) has become a global problem. Role of n-3 FA in its prevention is still not

completely understood. We carried out this systematic review and meta-analysis to assess the relation of dietary intake of fish and n-3PUFA with risk of diabetes. We searched PUBMED, EMBASE and GOOGLE with cross references to identify relevant articles. Since no RCTs were available, we searched for prospective cohort studies. Sixteen studies with 6,79,763 participants which assessed the association of dietary intake of fish and n-3 PUFA (marine or alpha-linolenic acid) with incidence of T2DM in > 18 years population and provided relative risk (RR) or hazard ratio (HR) with the corresponding 95% confidence interval (CI) of T2DM for each category of fish or n-3 PUFA intake were included. Three independent reviewers reviewed all eligible studies and abstracted the relevant information from individual studies. Meta-analysis confirmed the previous finding that marine n-3 FA increased risk of T2DM in Americans but reduced the same in Asians. We observed that two and seven times increased intake of ALA and fatty fish respectively reduced the risk of T2DM significantly and ALA did not increase the risk in Americans. We concluded that ALA may have some role in preventing T2DM, but is not studied widely. Hence, it should be studied in greater details (with higher degrees of intake; more than two times) to aid in developing effective preventive strategies against diabetes.

Naumann J, Biehler D, Luty T,Sadaghiani C. Prevention and Therapy of Type 2 Diabetes-What Is the Potential of Daily Water Intake and Its Mineral Nutrients? Nutrients 2017;9(8):22 We aim to present an overview of the possible influence of drinking water in general and mineral water in

particular in improving glycemic parameters in persons with or without type 2 diabetes. We performed a literature search that produced 15 randomized controlled trials (RCTs) on this topic with mainly small sample sizes. We also discuss relevant observational and animal studies as well as the effects of important supplements in mineral water such as hydrogencarbonate and magnesium. There is low evidence for the positive effects of water or mineral water in improving glycemic parameters in diabetic and non-diabetic persons, and the results are heterogenous, making it difficult to reach an unequivocal conclusion. Meta-analyses of prospective cohort studies and other observational studies, studies with animal models and interventional studies using hydrogencarbonate and magnesium supplements suggest a probable positive effect of drinking water and mineral water in particular on glycemic parameters, supporting the positive results found in some of the RCTs, especially those substituting diet beverages or caloric beverages with water, or those using bicarbonate and magnesium-rich water. Regarding the high prevalence, the associated suffering and the resulting health expenditures of type 2 diabetes, it is imperative to conduct larger and more rigorous trials to answer the question whether drinking water or mineral water can improve glycemic parameters in diabetic and non-diabetic persons.

Neamah HH, Sebert Kuhlmann AK,Tabak RG. Effectiveness of Program Modification Strategies of the Diabetes Prevention Program: A Systematic Review. Diabetes Educator 2016;42(2):153-65 PURPOSE: The purpose of this study is to review the effectiveness of commonly used program

36

modifications classified under cultural adaptation and program translational strategies for the Diabetes Prevention Program (DPP) in terms of risk reduction for type 2 diabetes.

METHODS: Authors extracted data about weight, body mass index (BMI), and 5 areas of program modification strategies from 28 interventions and analyzed them in SPSS software. Bivariate analyses examined the odds of achieving a significant reduction in outcomes by each modification of the DPP and by presence of a maintenance component, as well as the mean reduction of weight and BMI by more versus fewer modifications and by the presence of a maintenance component.

RESULTS: There were no statistically significant differences in achieving a significant reduction in weight or BMI by any type of modification or by the presence of a maintenance component. Programs with fewer modifications reported significantly greater reduction in mean weight at 12 months postintervention and the furthest time point extracted. Programs with a maintenance component achieved significantly greater reduction in mean weight measured at the furthest time point extracted.

CONCLUSIONS: The DPP appears to be programmatically robust to a variety of cultural adaptation and translational strategies. Potentially cost-saving modifications do not seem to reduce effectiveness, which should encourage implementation on a broader scale. Program planners should, however, make efforts to include maintenance components because they appear to significantly reduce risk for acquiring type 2 diabetes.

Nieto-Martinez R, Gonzalez-Rivas JP, Aschner P, Barengo NC,Mechanick JI. Transculturalizing Diabetes Prevention in Latin America. Annals of Global Health 2017;83(3-4):432-443 BACKGROUND: Type 2 diabetes (T2D) imposes a heavy burden in developing countries, requiring

effective primary prevention policies. Randomized clinical trials have identified successful strategies in T2D prevention. However, translating these results to real-life scenarios and adapting to ethnocultural differences is a major challenge. Transculturalization allows incorporating cultural factors to diabetes prevention strategies to optimize implementation of clinical trials results. The purpose of this paper is to review the transcultural adaptations developed for T2D prevention in Latin America (LA).

METHODS: A comprehensive literature review spanning 1960-2016 was performed, using "Diabetes," "Latin America," "Prevention," "Screening," and "Tools" as key words.

RESULTS: Two major tasks are underway in LA: adaptation of screening tools for high-risk individuals, and implementation of diabetes prevention programs. The Finnish Diabetes Risk Score (FINDRISC) is the most widely used screening tool to detect new cases of T2D and people with prediabetes, and it has been adapted (LA-FINDRISC) to include the waist circumference cutoff values appropriate for LA population (>=94 cm for men and >=90 cm for women). The validation of the LA-FINDRISC performance depends on the local characteristics. A LA-FINDRISC score >10 may be the best cutoff to identify individuals with impaired glucose regulation in population-based studies, but a higher score (>12-14) might be more appropriate in a clinical setting. A shorter version of the FINDRISC using only the 4 variables with highest impact has been developed and validated in Colombia (ColDRISC). The translation of the Diabetes Prevention Program study in a Latino population in Venezuela found a significant improvement in cardiometabolic risk factors. An adaptation of the Diabetes Prevention Study in the DEMOJUAN study in Barranquilla, Colombia, reduced 2-hour postload glucose.

CONCLUSION: Successful transculturalization strategies have been implemented in screening tools and prevention programs in LA.

Panunzi S, De Gaetano A, Carnicelli A,Mingrone G. Predictors of remission of diabetes mellitus in severely obese individuals undergoing bariatric surgery: do BMI or procedure choice matter? A meta-analysis. Annals of Surgery 2015;261(3):459-67 OBJECTIVE: To compare diabetes remission after bariatric surgery in subjects with body mass index (BMI)

of 35 kg/m2 or more or BMI of less than 35 kg/m to determine which predictors are best. BACKGROUND: BMI is currently the only selection criterion for bariatric surgery in diabetic subjects. Many studies

have challenged BMI for predicting diabetes remission. METHODS: Data sources were PubMed, Cochrane Library, and EMBASE databases from January 1980 to June

2013. The selected studies were randomized controlled trials, controlled clinical trials, or cohort studies with 10 or more patients per arm. Of 1437 screened articles, 94 studies were included with 94,579 patients undergoing surgical procedures (4944 with type 2 diabetes mellitus). Weight, BMI, glycated hemoglobin A1c, fasting glucose, and insulin were abstracted by 2 independent reviewers. The effect size was the percent diabetes remission.

RESULTS: Meta-analysis was performed for BMI less than 35 kg/m2 (group 1) and BMI 35 kg/m2 or more (group 2). Diabetes remission was 72% [95% confidence interval (CI), 65-80] in group 1 and 71% (95% CI, 65-77) in group 2. Diabetes resolution was 89% (95% CI, 83-94) after biliopancreatic diversion, 77% (95% CI, 72-82) after Roux-en-Y bypass, 62% (95% CI, 46-79) after gastric banding, and 60% (95% CI, 51-70) after sleeve gastrectomy. The only significant predictor of glycated hemoglobin A1c reduction was waist circumference, lower baseline waist associating with higher reduction.

CONCLUSIONS: Bariatric surgery determines similar diabetes remission rates in patients with BMI of 35 kg/m2 or more or BMI of less than 35 kg/m2. Baseline BMI is unrelated to diabetes remission. The association of

37

baseline waist circumference with glycated hemoglobin A1c reduction is likely due to selection bias. Bariatric or metabolic effects of the surgical procedures appear independent, and different indices are needed to predict them.

Parackal S. Dietary Transition in the South Asian Diaspora: Implications for Diabetes Prevention Strategies. Current Diabetes Reviews 2017;13(5):482-487 BACKGROUND: South Asians (SA) have a four to five fold higher risk for type 2 diabetes mellitus (T2DM)

in comparison to other Asian migrant groups. Dietary patterns have been attributed as an important independent modifiable risk factor.

OBJECTIVE: The aim of this review is to document the dietary patterns of SA migrants in Western countries and to summarize the evidence for the association of dietary patterns with T2DM and its predisposing factors.

METHODS: Using key search words articles from 1990 onwards were sourced from MEDLINE Pro- Quest and PubMed (not MEDLINE) databases for this narrative review.

RESULTS: A significant shift in meal pattern with frequent dining out and eating fast foods, traditional festival foods and Western desserts and snacks was common among SA. Consumption of potatoes, dairy, oil, meat and fish increased and beans, lentils, fruits and vegetables decreased post-migration. "Animal protein" and "fried snacks, sweets and high-fat dairy" were associated with greater insulin resistance and lower HDL cholesterol. A "mixed" dietary pattern was associated with obesity and hypertension and a "western" dietary pattern was associated with overall risk for Metabolic Syndrome. A 70% increase in the odds of diabetes per standard deviation in gram of protein intake was also observed.

CONCLUSION: Dietary patterns pave the way to develop diabetes and other obesity related diseases among SA as duration of residence increases. The first five years since migration maybe a window of opportunity to provide targeted interventions to ensure maintenance of healthy dietary habits.

Raynor HA, Davidson PG, Burns H, Nadelson MDH, Mesznik S, Uhley V, et al. Medical Nutrition Therapy and Weight Loss Questions for the Evidence Analysis Library Prevention of Type 2 Diabetes Project: Systematic Reviews. Journal of the Academy of Nutrition & Dietetics 2017;117(10):1578-1611 BACKGROUND: Eleven recommendations, based on systematic reviews, were developed for the

Evidence Analysis Library's prevention of type 2 diabetes project. Two recommendations, medical nutrition therapy (MNT) and weight loss, were rated strong.

OBJECTIVE: Present the basis of systematic reviews for MNT and weight loss recommendations. METHODS: Literature searches using Medline were conducted to identify studies that met eligibility criteria. The

MNT literature search covered a time span of 1995 to 2012, the weight loss literature search covered 2008 to 2012 due to inclusion of a Cochrane Review meta-analysis of randomized controlled trials (RCTs) published in 2008. Eligibility criteria for inclusion of articles included original research using higher-quality study designs (ie, RCTs, case control, cohort, crossover, and nonrandomized trials) with participants aged >18 years and meeting prediabetes or metabolic syndrome diagnostic criteria. MNT was defined as individualized and delivered by a registered dietitian nutritionist or international equivalent and length of weight loss interventions was >=3 months.

MAIN OUTCOME MEASURES: Two-hour postprandial blood glucose level, glycated hemoglobin level, albumin-to-creatinine ratio (metabolic syndrome samples only), fasting blood glucose level, high-density lipoprotein cholesterol level, systolic and diastolic blood pressure, triglyceride levels, urinary albumin excretion rate (metabolic syndrome samples only), waist circumference (WC), and waist-to-hip ratio were evaluated.

RESULTS: For MNT, 11 publications were included, with all 11 using an RCT study design and 10 including participants with prediabetes. A majority of publications reported significant improvements in glycemic outcomes, WC, and blood pressure. For weight loss, 28 publications were identified, with one meta-analysis (only included RCTs) and 20 publications using an RCT study design, with the meta-analysis and 10 RCTs including participants with prediabetes. A majority of publications reported significant improvements in glycemic outcomes, triglyceride level, WC, and blood pressure.

CONCLUSIONS: Systematic reviews provided strong evidence that MNT and weight loss alter clinical parameters in ways that should reduce the risk of developing type 2 diabetes.

Roberts S, Barry E, Craig D, Airoldi M, Bevan G,Greenhalgh T. Preventing type 2 diabetes: systematic review of studies of cost-effectiveness of lifestyle programmes and metformin, with and without screening, for pre-diabetes. BMJ Open 2017;7(11):e017184 OBJECTIVE: Explore the cost-effectiveness of lifestyle interventions and metformin in reducing

subsequent incidence of type 2 diabetes, both alone and in combination with a screening programme to identify high-risk individuals.

DESIGN: Systematic review of economic evaluations. DATA SOURCES AND ELIGIBILITY CRITERIA: Database searches (Embase, Medline, PreMedline, NHS EED)

and citation tracking identified economic evaluations of lifestyle interventions or metformin alone or in combination with screening programmes in people at high risk of developing diabetes. The International Society for Pharmaco-economics and Outcomes Research's Questionnaire to Assess Relevance and Credibility of Modelling Studies for Informing Healthcare Decision Making was used to assess study

38

quality. RESULTS: 27 studies were included; all had evaluated lifestyle interventions and 12 also evaluated metformin.

Primary studies exhibited considerable heterogeneity in definitions of pre-diabetes and intensity and duration of lifestyle programmes. Lifestyle programmes and metformin appeared to be cost effective in preventing diabetes in high-risk individuals (median incremental cost-effectiveness ratios of 7490/quality-adjusted life-year (QALY) and 8428/QALY, respectively) but economic estimates varied widely between studies. Intervention-only programmes were in general more cost effective than programmes that also included a screening component. The longer the period evaluated, the more cost-effective interventions appeared. In the few studies that evaluated other economic considerations, budget impact of prevention programmes was moderate (0.13%-0.2% of total healthcare budget), financial payoffs were delayed (by 9-14 years) and impact on incident cases of diabetes was limited (0.1%-1.6%reduction). There was insufficient evidence to answer the question of (1) whether lifestyle programmes are more cost effective than metformin or (2) whether low-intensity lifestyle interventions are more cost effective than the more intensive lifestyle programmes that were tested in trials.

CONCLUSIONS: The economics of preventing diabetes are complex. There is some evidence that diabetes prevention programmes are cost effective, but the evidence base to date provides few clear answers regarding design of prevention programmes because of differences in denominator populations, definitions, interventions and modelling assumptions.

Samuel-Hodge CD, Johnson CM, Braxton DF,Lackey M. Effectiveness of Diabetes Prevention Program translations among African Americans. Obesity Reviews 2014;15 Suppl 4(107-24 The Diabetes Prevention Program (DPP) demonstrated risk reduction for incident diabetes through weight

loss among all participants, including African Americans. Several DPP translations have been conducted in less controlled settings, including primary care practices and communities; however, there is no detailed compilation of how effective these translations have been for African Americans. This systematic literature review evaluated DPP translations from 2003 to 2012. Eligible records were retrieved using a search strategy of relevant databases and gray literature. Retrieved records (n=1,272) were screened using a priori criteria, which resulted in 21 full-text studies for review. Seventeen studies were included in the full-text qualitative synthesis. Seven studies had 100% African American samples and 10 studies had mixed samples with African American subgroups. African American participants' average weight loss was roughly half of that achieved in the DPP intervention. However, with few higher-quality studies, small sample sizes and differences in intervention designs and implementation, comparisons across interventions were difficult. The suboptimal effectiveness of DPP translations among African American adults, particularly women, signals the need for enhancements to existing evidence-based interventions and more high-quality research that includes other at-risk African American subgroups such as men and younger adults of lower socioeconomic status.

Schwingshackl L, Lampousi AM, Portillo MP, Romaguera D, Hoffmann G,Boeing H. Olive oil in the prevention and management of type 2 diabetes mellitus: a systematic review and meta-analysis of cohort studies and intervention trials. Nutrition & Diabetes 2017;7(4):e262 BACKGROUND/OBJECTIVES: Olive oil (OO) as food is composed mainly of fatty acids and bioactive

compounds depending from the extraction method. Both had been discussed as health promoting with still open questions. Thus, we conducted a meta-analysis to illustrate the impact of this food on type 2 diabetes (T2D) by investigating the association between OO intake and risk of T2D, and the effect of OO intake in the management of T2D.

SUBJECTS/METHODS: Searches were performed in PubMed, Cochrane Library and google scholar. First, we conducted a random effect meta-analysis of prospective cohort studies and trials investigating the association between OO and risk of T2D. Second, a meta-analysis was performed to detect the effects of olive oil on glycemic control in patients with T2D.

RESULTS: Four cohort studies including 15784 T2D cases and 29 trials were included in the meta-analysis. The highest OO intake category showed a 16% reduced risk of T2D (RR: 0.84; 95% CI: 0.77, 0.92) compared with the lowest. However, we observed evidence for a nonlinear relationship. In T2D patients OO supplementation resulted in a significantly more pronounced reduction in HbA1c (MD: -0.27%; 95% CI: -0.37, -0.17) and fasting plasma glucose (MD: -0.44mmoll^-1; 95% CI -0.66, -0.22) as compared with the control groups.

CONCLUSIONS: This meta-analysis provides evidence that the intake of OO could be beneficial for the prevention and management of T2D. This conclusion regards OO as food, and might not been valid for single components comprising this food.

Seida JC, Mitri J, Colmers IN, Majumdar SR, Davidson MB, Edwards AL, et al. Clinical review: Effect of vitamin D3 supplementation on improving glucose homeostasis and preventing diabetes: a systematic review and meta-analysis. Journal of Clinical Endocrinology & Metabolism 2014;99(10):3551-60 CONTEXT: Observational studies report consistent associations between low vitamin D concentration and

increased glycemia and risk of type 2 diabetes, but results of randomized controlled trials (RCTs) are

39

mixed. OBJECTIVE: The objective of the study was to systematically review RCTs that report on the effects of vitamin D

supplementation on glucose homeostasis or diabetes prevention. DATA SOURCES: Sources of data for the study were MEDLINE, EMBASE, SCOPUS, Cochrane Database of

Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment, and Science Citation Index from inception to June 2013.

STUDY SELECTION: Study selection was trials that compared vitamin D3 supplementation with placebo or a non-vitamin D supplement in adults with normal glucose tolerance, prediabetes, or type 2 diabetes.

DATA EXTRACTION AND SYNTHESIS: Two reviewers collected data and assessed trial quality using the Cochrane Risk of Bias tool. Random-effects models were used to estimate mean differences (MDs) and odds ratios. The main outcomes of interest were homeostasis model assessment of insulin resistance, homeostasis model assessment of beta-cell function, hemoglobin A1c levels, fasting blood glucose, incident diabetes, and adverse events.

DATA SYNTHESIS: Thirty-five trials (43 407 patients) with variable risk of bias were included. Vitamin D had no significant effects on insulin resistance [homeostasis model assessment of insulin resistance: MD -0.04; 95% confidence interval (CI) -0.30 to 0.22, I-squared statistic (I(2)) = 45%], insulin secretion (homeostasis model of beta-cell function: MD 1.64; 95% CI -25.94 to 29.22, I(2) = 40%), or hemoglobin A1c (MD -0.05%; 95% CI -0.12 to 0.03, I(2) = 55%) compared with controls. Four RCTs reported on the progression to new diabetes and found no effect of vitamin D (odds ratio 1.02; 95% CI 0.94 to 1.10, I(2) = 0%). Adverse events were rare, and there was no evidence of publication bias.

CONCLUSIONS: Evidence from available trials shows no effect of vitamin D3 supplementation on glucose homeostasis or diabetes prevention. Definitive conclusions may be limited in the context of the moderate degree of heterogeneity, variable risk of bias, and short-term follow-up duration of the available evidence to date.

Sheng B, Truong K, Spitler H, Zhang L, Tong X,Chen L. The Long-Term Effects of Bariatric Surgery on Type 2 Diabetes Remission, Microvascular and Macrovascular Complications, and Mortality: a Systematic Review and Meta-Analysis. Obesity Surgery 2017;27(10):2724-2732 This systematic review aimed to evaluate the long-term (>= 5 years) outcomes of bariatric surgery on

diabetes remission, microvascular and macrovascular events, and mortality among type 2 diabetes (T2D) patients. Ten articles (one randomized controlled trial and nine cohorts) met the inclusion criteria and were included in this review. Pooled estimates of nine cohort studies showed that surgery significantly increased the diabetes remission (relative risk (RR) = 5.90; 95% CI 3.75-9.28), reduced the microvascular (RR = 0.37; 95% CI = 0.30-0.46) and macrovascular events (RR = 0.52; 95% CI 0.44-0.61), and mortality (RR = 0.21; 95% CI 0.20-0.21) as compared to non-surgical treatment. Available evidence suggests better remission and lower risks of microvascular and macrovascular disease and mortality in the surgery group as compared to non-surgical treatment group in T2D patients after at least 5 years of follow-up.

Stevens JW, Khunti K, Harvey R, Johnson M, Preston L, Woods HB, et al. Preventing the progression to type 2 diabetes mellitus in adults at high risk: a systematic review and network meta-analysis of lifestyle, pharmacological and surgical interventions. Diabetes Research & Clinical Practice 2015;107(3):320-31 AIMS: Individuals with impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) have an

increased risk of progression to Type 2 diabetes mellitus. The objective of this review was to quantify the effectiveness of lifestyle, pharmacological and surgical interventions in reducing the progression to Type 2 diabetes mellitus in people with IFG or IGT.

METHODS: A systematic review was carried out. A network meta-analysis (NMA) of log-hazard ratios was performed. Results are presented as hazard ratios and the probabilities of treatment rankings.

RESULTS: 30 studies were included in the NMA. There was a reduced hazard of progression to Type 2 diabetes mellitus associated with all interventions versus standard lifestyle advice; glipizide, diet plus pioglitazone, diet plus exercise plus metformin plus rosiglitazone, diet plus exercise plus orlistat, diet plus exercise plus pedometer, rosiglitazone, orlistat and diet plus exercise plus voglibose produced the greatest effects.

CONCLUSIONS: Lifestyle and some pharmacological interventions are beneficial in reducing the risk of progression to Type 2 diabetes mellitus. Lifestyle interventions require significant behaviour changes that may be achieved through incentives such as the use of pedometers. Adverse events and cost of pharmacological interventions should be taken into account when considering potential risks and benefits.

Sun Y, You W, Almeida F, Estabrooks P,Davy B. The Effectiveness and Cost of Lifestyle Interventions Including Nutrition Education for Diabetes Prevention: A Systematic Review and Meta-Analysis. Journal of the Academy of Nutrition & Dietetics 2017;117(3):404-421.e36 BACKGROUND: Type 2 diabetes is a significant public health concern. With the completion of the

Diabetes Prevention Program, there has been a proliferation of studies attempting to translate this evidence base into practice. However, the cost, effectiveness, and cost-effectiveness of these adapted interventions is unknown.

OBJECTIVE: The purpose of this systematic review was to conduct a comprehensive meta-analysis to synthesize

40

the effectiveness, cost, and cost-effectiveness of lifestyle diabetes prevention interventions and compare effects by intervention delivery agent (dietitian vs non-dietitian) and channel (in-person vs technology-delivered).

METHODS: English and full-text research articles published up to July 2015 were identified using the Cochrane Library, PubMed, Education Resources Information Center, CAB Direct, Science Direct, and Google Scholar. Sixty-nine studies met inclusion criteria. Most employed both dietary and physical activity intervention components (four of 69 were diet-only interventions). Changes in weight, fasting and 2-hour blood glucose concentration, and hemoglobin A1c were extracted from each article. Heterogeneity was measured by the I² index, and study-specific effect sizes or mean differences were pooled using a random effects model when heterogeneity was confirmed.

RESULTS: Participants receiving intervention with nutrition education experienced a reduction of 2.07 kg (95% CI 1.52 to 2.62; P<0.001; I²=90.99%, 95% CI 88.61% to 92.87%) in weight at 12 months with effect sizes over time ranging from small (0.17, 95% CI 0.04 to 0.30; P=0.012; I²= 86.83%, 95% CI 80.42% to 91.14%) to medium (0.65, 95% CI 0.49 to 0.82; P<0.001; I²=98.75%, 95% CI 98.52% to 98.94). Effect sizes for 2-hour blood glucose and hemoglobin A1c level changes ranged from small to medium. The meta-regression analysis revealed a larger relative weight loss in dietitian-delivered interventions than in those delivered by nondietitians (full sample: -1.0 kg; US subsample: -2.4 kg), and did not find statistical evidence that the delivery channel was an important predictor of weight loss. The average cost per kilogram weight loss ranged from $34.06 over 6 months to $1,005.36 over 12 months. The cost of intervention per participant delivered by dietitians was lower than interventions delivered by non-dietitians, although few studies reported costs.

CONCLUSIONS: Lifestyle interventions are effective in reducing body weight and glucose-related outcomes. Dietitian-delivered interventions, compared with those delivered by other personnel, achieved greater weight reduction. No consistent trend was identified across different delivery channels.

Tan XY,Hu JB. ACEIs/ARBs for the prevention of type 2 diabetes in patients with cardiovascular diseases: A systematic review and meta-analysis. International Journal of Clinical and Experimental Medicine 2016;9(6):9628-9641 Purpose: Several studies have demonstrated that angiotensin-converting enzyme inhibitors (ACEIs) and

angiotensin receptor blockers (ARBs) reduce the incidence of type 2 diabetes in patients with cardiovascular diseases. Therefore, a systematic review and meta-analysis was performed to assess the clinical efficacy of ACEIs and ARBs in preventing type 2 diabetes. Methods: Randomized controlled trials (RCTs) were retrieved from PubMed, Embase, the Cochrane Library and Clinical Trials go through August 2015. Two reviewers independently assessed search results, extracted data, and appraised risk of bias. Results: A total of 21 studies met the inclusion criteria with a total of 111,768 subjects. Thereinto, 55962 patients randomly received ACEIs or ARBs, and 55824 received anti-hypertensive agents or a placebo. ACEIs and ARBs were associated with reductions in the incidence of newly diagnosed type 2 diabetes (ACEIs RR 0.76, 95% CI 0.67-0.87, P < 0.001; ARBs RR 0.79, 95% CI 0.74-0.85, P < 0.001; pooled analysis RR 0.78, 95% CI 0.73-0.84, P < 0.001). Conclusions: ACEIs or ARBs can reduce the incidence of type 2 diabetes, especially in patients with hypertension, metabolic syndrome, pre-diabetes phase, congestive heart failure, or coronary heart disease. ACEIs or ARBs is accordingly recommended as the first line antihypertensive agents in patients with cardiovascular diseases. Copyright © 2016, E-Century Publishing Corporation. All rights reserved.

Taylor J, Cottrell C, Chatterton H, Hill J, Hughes R, Wohlgemuth C, et al. Identifying risk and preventing progression to Type 2 diabetes in vulnerable and disadvantaged adults: a pragmatic review. Diabetic Medicine 2013;30(1):16-25 AIM: To identify effective approaches to recognize diabetes risk and prevent progression to Type 2

diabetes in vulnerable groups, whose diabetes risk may be difficult to identify or manage. METHODS: UK-based interventions that assess diabetes risk and/or target known risk factors were identified

through four main sources: submissions to two calls for evidence by the National Institute for Health and Clinical Excellence; local practice examples collected via a targeted email questionnaire; selected electronic databases; and a focused search of relevant websites. No restriction was placed on the study type or evaluation methods used. Key themes and sub-themes on outcomes, as well as facilitators and barriers to successful delivery, are reported.

RESULTS: Twenty-four interventions met all inclusion criteria: 15 included a risk identification element and 14 included preventative activities. A range of risk identification tools were used to improve diagnosis of unmet diabetes-related health needs and raise awareness of diabetes risk factors. All preventative interventions focused on lifestyle change. No interventions monitored blood glucose as an outcome and only one reported improvements in baseline risk scores. Facilitators included tailored and flexible programme design, outreach delivery in familiar locations and effective inter-agency working. Barriers included literacy and language difficulties, transient participant populations, low prioritization of diabetes prevention and cost.

CONCLUSIONS: It is possible to engage successfully with high-risk adults in vulnerable groups to achieve positive

41

health outcomes relevant to the prevention of diabetes. However, more robust evidence on longer-term outcomes is required to ensure that programmes are targeted and delivered appropriately.

Wang GF, Yan YX, Xu N, Yin D, Hui Y, Zhang JP, et al. Predictive factors of type 2 diabetes mellitus remission following bariatric surgery: a meta-analysis. Obesity Surgery 2015;25(2):199-208 BACKGROUND: Although a few studies have been reported on predictive factors of postoperative

diabetes remission, the conclusions remain inconsistent. This meta-analysis aimed to assess the preoperative clinical factors for type 2 diabetes mellitus (T2DM) remission after bariatric surgery.

METHODS: The Cochrane Library, PubMed, MEDLINE, Embase, and CINAHL databases were searched. All human studies published in English between 1 January 1992 and 1 September 2013 reporting on the parameters of interest were included.

RESULTS: In total, 15 studies involving 1,753 bariatric surgery patients were selected. Analyses were performed separately for the parameters of interest. T2DM remission was observed to be negatively correlated with age, diabetes duration, insulin use, and HbA1c levels. Baseline body mass index (BMI) and C-peptide levels were positively associated with the remission rate in Asian patients. However, there was no significant association between gender and remission rate.

CONCLUSIONS: Patients with younger age, short diabetes duration, better glucose control, and better beta cell function were more likely to achieve T2DM remission after bariatric surgery. However, further randomized controlled trials with uniform remission criteria should be conducted to provide more reliable evidence.

Watson P, Preston L, Squires H, Chilcott J,Brennan A. Modelling the economics of type 2 diabetes mellitus prevention: a literature review of methods. Applied Health Economics & Health Policy 2014;12(3):239-53 Our objective was to review modelling methods for type 2 diabetes mellitus prevention cost-effectiveness

studies. The review was conducted to inform the design of a policy analysis model capable of assisting resource allocation decisions across a spectrum of prevention strategies. We identified recent systematic reviews of economic evaluations in diabetes prevention and management of obesity. We extracted studies from two existing systematic reviews of economic evaluations for the prevention of diabetes. We extracted studies evaluating interventions in a non-diabetic population with type 2 diabetes as a modelled outcome, from two systematic reviews of obesity intervention economic evaluations. Databases were searched for studies published between 2008 and 2013. For each study, we reviewed details of the model type, structure, and methods for predicting diabetes and cardiovascular disease. Our review identified 46 articles and found variation in modelling approaches for cost-effectiveness evaluations for the prevention of type 2 diabetes. Investigation of the variables used to estimate the risk of type 2 diabetes suggested that impaired glucose regulation, and body mass index were used as the primary risk factors for type 2 diabetes. A minority of cost-effectiveness models for diabetes prevention accounted for the multivariate impacts of interventions on risk factors for type 2 diabetes. Twenty-eight cost-effectiveness models included cardiovascular events in addition to type 2 diabetes. Few cost-effectiveness models have flexibility to evaluate different intervention types. We conclude that to compare a range of prevention interventions it is necessary to incorporate multiple risk factors for diabetes, diabetes-related complications and obesity-related co-morbidity outcomes.

Yan W, Bai R, Yan M,Song M. Preoperative Fasting Plasma C-Peptide Levels as Predictors of Remission of Type 2 Diabetes Mellitus after Bariatric Surgery: A Systematic Review and Meta-Analysis. Journal of Investigative Surgery 2017;30(6):383-393 AIMS: The study evaluated the predictive role of preoperative fasting C-peptide, hemoglobin (Hb)A1c,

fasting plasma glucose (FPG), and body mass index (BMI) levels on diabetes remission in patients with type 2 diabetes following bariatric surgery.

METHODS: Medline, PubMed, Central, and Google Scholar databases of up to September 7, 2016 were searched using the following terms: type 2 diabetes mellitus, gastric bypass, Roux-en-Y, anastomosis, C-peptide, weight loss, HbA/HbA1c, predictive/predictor.

RESULTS: Meta-analysis of the pooled data indicated that fasting C-peptide was predictive of increased chance of remission of type 2 diabetes (pooled difference in means = 0.93, 95% confidence interval [CI] = 0.61 to 1.25, p < .001). The analysis also found that FPG (pooled standardized mean difference = -0.42, 95% CI: -0.64 to -0.20, p < .004) and HbA1c levels (pooled difference in means = -1.05, 95% CI: -1.48 to -0.62, p < .001) were associated with reduced odds of type 2 diabetes remission. BMI was not found to be associated with remission (pooled difference in means = 0.29, 95% CI: 0.30 to 0.88, p = .343). In general, subgroup analysis, which evaluated the pooled data from the retrospective and prospective studies separately, gave similar results.

CONCLUSIONS: Preoperative fasting plasma C-peptide was associated with increased type 2 diabetes remission after bariatric surgery, whereas baseline HbA1c and FPG levels were associated with reduced chance of remission. These parameters may be used as a guideline in weighing the risks and benefits for surgical intervention in patients with type 2 diabetes.

Yan YX, Wang GF, Xu N,Wang FL. Correlation between postoperative weight loss and diabetes mellitus remission:

42

a meta-analysis. Obesity Surgery 2014;24(11):1862-9 OBJECTIVE: This meta-analysis was conducted to determine the effect of percent excess weight loss

(%EWL) after bariatric surgery on diabetes remission. METHODS: The Cochrane Library, PubMed, MEDLINE, Embase, and CINAHL were searched. All reports on

%EWL involving humans and published in English between 1 January 1992 and 1 September 2013 were included in the analysis.

RESULTS: Eight studies involving 1,247 patients who underwent bariatric surgery were selected. %EWL was positively associated with remission rate (WMD = 11.15, 95 % CI: 6.73-15.56, p < 0.01) in the Caucasian population.

CONCLUSIONS: Patients with extensive weight loss were more likely to achieve T2DM remission after bariatric surgery. Further randomized controlled trials (RCTs) with uniform remission criterion should be performed to provide more reliable evidence.