1) diabetes epidemic 2) outcome measures in diabetes 23.9.11

8/3/2019 1) Diabetes Epidemic 2) Outcome Measures in Diabetes 23.9.11

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Diabetes Epidemic in India:

Is it subsiding?


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TOP TEN COUNTRIES FOR THEIR

ESTIMATED NUMBER OF ADULTS

WITH DIABETES(IN MILLIONS).

Country Year 1995 Year 2025

India

China

U.S.A.

Russian

Federation

Japan

Brazil

Indonesia

Pakistan

19.4

16.013.9

8.9

6.3

4.9

4.5

4.3

57.2

37.621.9

12.2

8.5

11.6

12.4

14.52


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3

STUDIES OF PREVALENCE OF DM IN INDIA

FROM 19792001YEAR AUTHOR PLACE PREVALANCE RATE

19861988

1989

1989

19911992

1997

1999

20002001

Patel J. C.Ramchandran et al

Kodali et al

Rao et al

Ahuja et alRamchandran et al

Ramchandran et al

Ashabai et al

Ramchandran et al(DESI)

Misra et al

BhadranKudremkh

Gangarathi

Eluru

New DelhiMadras

Madras

Chennai

National

Northern India

3.8 ( R )5.0 ( U )

2.2 ( R )

1.6 ( R )

6.7 ( R )8.2 ( U )/2.4 ( R )

11.6 ( U )

17.4% ( U )

12.1 ( U )

10.3 DM

15.2 IFG

U = Urban IFG = Impaired Fasting GlucoseR = Rural DESI = Diabetes E idemic Studies in India

3


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4

ESTIMATED PREVALENCE IN

URBAN AND RURAL INDIA

0

10

20

30

40

50

60

1990

1995

2000

2005

2010

2015

2020

2025

UrbanRural

Number (millions)

4


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Chennai Urban Rural Epidemiological Study (CURES- 17)(Diabetologia 2006)

Prevalence of Diabetes in Chennai rose by:

39.8% in years 1989 1995

16.3% in years 1995 2000

6% in years 2000 2004


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Factors likely to influence prevalence oftype 2 diabetes

Factors Factor likely toincrease prevalence

Factor likely todecrease prevalence

1 Demography ofthe

population

Increasing life span Increase in younger agegroups

2 Obesity Increasing obesity Decreasing obesity

3 Education Continuing lower educationalstatus

Rapidly increasing generaland health education

4 Income Increasing income

(specially when accompanied

by poor educational inputs)

Increasing income(specially whenaccompanied byenhancededucational inputs)


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Factors likely to influence prevalence of type2 diabetes

5 Genetic factors Increased prevalencetill adverseenvironment has actedon most geneticallysusceptible population

Stabilizing influence ofgenetically non-susceptiblegroup

6 Physical activity Decreased activity dueto urbanization and

poor built environment

Increased physical activity byintroducing healthylifestylethrough education and bettertown planning

7 Diet Increased calories,

saturated fat, sugarand

refined food intake

Decreased calories, saturated

fat, sugar and refinedfood intake

8 Mental stress High stress with poorquality of life

Peaceful and good quality of life


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Percentage distribution of 2001 censuspopulation for India

Age Group Persons(%)0-4 11.8

5-9 12.0

10-14 11.7

15-19 10.1

20-24 8.925-29 8.1

30-34 7.4

35-39 6.6

40-44 5.6

45-49 4.6

50-54 3.6

55-59 2.9

60-64 2.5

65-69 2.0

70-74 1.6

75-79 0.5

80+ 0.3 Source: Population Projection report - 2006


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Demographic Structure (India, 2001)

Ages 0-19 45.6%

Ages 50-80 13.4%

9


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Is there possibility of second

epidemic of DM in India?

Yes: when the population structure changes in favourof elderly subjects

No: Education

Behavior changes

Town planning

may counter the epidemic

10


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Diabetes MellitusFactors influencing Incidence & Prevalence

11

Increased life span Increased elderly population

Decreased life spanIncreased young population

Prevalence

Birth & Death rate


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ECONOMIC DEVELOPMENT

AND OBESITYObese Percent of Population

Worldwide 8.2

Least developed countries 1.8

Developing Countries 4.8

Emerging Economies 17.1Developed Economies 20.4

( The Economist, Dec 2003)

HBC- DENMARC12


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BMI TRENDS IN FINLAND & INFLUENCE OFEDUCATION

(Pekkanen, J Epidemiol Commun Health, 1995) HBC- DENMARC13

With increasing education, BMI goes down


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SHORT TERM WEIGHT LOSS

IMPROVES INSULIN SENSITIVITY

0

5

10

15

20

2530

35

40

45

Before Weight Loss After Weight Loss

*

*P


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LIFESTYLE CHANGES PREVENT

TYPE 2 DIABETES

(Finnish study) (Toumilehto, NEJM, 2001)

N= 522, IGTInterventions :

F.U. 3.7 yrs

Control group

Lifestyle intervention : Weight reduction,

Fat and SFA, fibre

Results : Wt loss: Intervention group 3.5 kg, placebo 0.3 kg

Cumulative incidence of diabetes

Control group 23%

Intervention group 11% (58% reduction) 15


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DIABETES PREVENTION PROGRAM

(DPP) (NEJM, 2002)

n= 3234, IGT, mean age 51 yrs, BMI 34Interventions :

F.U. for 2.8 yrs

Placebo Metformin : 850 mg/day : 150 min/wk Exercise

Life style modifications : 7% wt. reduction

Results :

Incidence of Diabetes (Cases per 100 person/year)

Placebo : 11

Metformin 7.8 % (31% reduction)

Lifestyle Intervention 4.8 (58 % reduction) 16


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Built Environment(Pasala, Rao, Sridhar: Built Environment and Diabetes, International Journal of

Diabetes in Developing countries, 2010)

Environment modified by humans: Home,

School, Workplace, Highways, Urbansprawls

Accessibility to amenities, leisure

Pollution


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Genetics of Type 2 DM

18

Susceptibility Genes

Present : PrevalenceAbsent : Stabilising effect

Protective Geneseg: Nephropathy


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Outcome Measures in Diabetes


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Outcome measures

1. Hard and Soft end points define: outcome

2. Non-diabetic or diabetic controls

3. Adjudicated outcome

4. Primary and Secondary outcome

5. Number needed to save one life

6. Mechanism of favorable or adverse outcome

may be difficult to unravel


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Medical Records

1. Quality of records

2. Manual or Computerization: designed to yieldto detailed analysis

3. Casual and regular patients

4. Follow up reminders

5. Cohort follow up


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Significance of outcome measures

1. All treatments modalities should undergooutcome studies

eg: CV outcome with newer agents

Malignancy

2. Efficacy versus outcome

eg: Torcetrapiband HDL-C


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DCCT : Benefits of good glycemic control

Mean HbA1c in intensive group was 7.2 % vs 9.2

% in conventional control group

Intensive glycemic control reduced the risks of

Neuropathy by 57-69 %

Retinopathy by 54-76 %

Nephropathy by 34-56 %N Engl J Med 1991

23


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UKPDS : Benefits of good glycemic control

Intensive glucose control maintained a lower HbA1cover a period of 10 years with reduction in risk of :

33 % for albuminuria

25 % for microvascular end-points

24 % for cataract extraction

21 % for retinopathy

16 % for myocardial infarction

12 % for any diabetes-related end-point

24


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Kumamoto Study :Benefits of Good

Glycemic ControlIntensive glycemic control reduced the risks of

progression of :

Nephropathy by 70 % Retinopathy by 69 %

Macrovascular events by 54 %

Preserved nerve conduction velocity better

Hypoglycemia was rareOkhubo et al, Diab Res Clin Pract 1995;28:103-117

25

O A Q A A CO O G


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HOW ADEQUATELY ARE WE CONTROLLING

DIABETES MELLITUS?

Targets:

ADA 7%

ACCE 6.5%

The targets can only be achieved, if prandial

blood glucose is targeted

Gl i G l EASD


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Glycemic Goals: EASDTYPE 2 DMLow risk Arterial

riskMicrovascular

risk

HbA1c (DCCT

Standardized)

%Hb

6.5 >7.5

Venous plasma glucose

Fasting / pre-prandial

mg/dl=110 >125

Self-monitored blood glucose

Fasting / pre-prandial

mg/dl=100 >=110

Post-prandial (peak)

mg/dl=135 >160

27

Gl cemic Go ls EASD


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Glycemic Goals-EASDTYPE 1 DM

Non-diabetic Adequate Inadequate

HbA1c (DCCT

standardized %Hb7.5

Self monitored blood glucose

Fasting/preprandial

mg/dl70-90 91-120 >120

Post-prandial (peak)

mg./dl70-135 136-160 >160

Pre-bed mg/dl 70-90 110-135 >135

It can be dangerous to strive for non-diabetic glucose levels.28


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HBA1C GOALS

Targets:

In general: HbA1c


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Only 26% of all type 2 diabetics inGermany achieve HbA1c < 6.5%

(Leibl A et al. CODE

2 Study, 2001)

Average HbA1c in US, 8.5-9.0%

(ADA, Diabetes Care 2000)

Global Scenario

DENMARC


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Global status of Glycemic control

1. Canada: Prim care; Mean HbA1c: 7.3 %

49 % not at target (A1c 7%)

(Harris, Diab Res Clin Pract, 2005)

2. Finland: 76 clinics; Mean HbA1c 8.6 1.9 %

(Type 1: 8.8, Type 2: 8.5) Lowest HbA1cvalues associated with short duration of DM

3. USA: NHANES III Preliminary report

HbA1c < 7 %: 44.5 % in 1988-94

35.5 % in 1999-2000

USA: 30 US academic centers: HbA1c


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PATIENTS AND METHODS

Type 2 DM on regular follow up (minimum

2 years)

2 study groups: group 1 DM 10 yrs (n =167), group 2 DM 10 yrs (n = 301)

Glycated hemoglobin done by total GHb or

HbA1c

;

results expressed as percent above

good control (good control GHb8%,HbA1c 7%).

32


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PATIENTS AND METHODS - 2

Initial GHb/HbA1c was compared with

average follow up values

average follow up 5.39 years (minimum 2

years)

average no. of GHb/HbA1c performed were

6.25/patient.

A total of 3400 values .

Paired t test used for data analysis.

33


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Patient CharacteristicsDENMARC DATA

Glycemic control

GHb/HbA1c (Above upper limit of good control)

Number of Patients: 330

Initial HbA1c ( n= 330 )(Mean SD) : 8.07 1.82

Number of Patients: 330

Average of subsequent HbA1c ( n= 465 )(Mean SD) : 8.01 0.59


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Change in Glycemic Control

GHb/HbA1c(MeanSD) n=468

p

Baseline Follow Up

Diabetes< 10 years

n=167

1.9

1.4 1.5

1.2 10 years

n=301

2.4

1.5 1.9

1.2


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Change in Glycemic ControlDENMARC DATA

(2007-2009)

GHb/HbA1c*

(Mean SD) n = 330

Baseline Follow Up2.22 0.67 1.33 0.22

*% above good glycemic control (HbA1c < 7.0%; GHb < 8.0%)

DENMARC

Diabetes Endocrine Nutrition Management and


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Diabetes Endocrine Nutrition Management andResearch Centre (DENMARC)

HbA1C achieved currently

27.30%

23.70%

49%8

9.7 1.34

6.2 0.5

7.5 0.31

Average of all values (n =1000):8.2 1.80 %


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HYPOGLYCEMIC AGENTS vs

ANTIHYPERGLYCEMIC AGENTS

Hypoglycemic agents Antihyperglycemic agents

Sulfonylureas

Non-SU insulin secretagogues Repaglinide

Nateglinide

Insulin

Metformin

Glitazone Nutrient blockers: acarbose,

voglibose, miglitol

GLP-1 analogues

DPP IV Inhibitors


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GLYCEMIC INDEX OF FOODS

Classification GI range Examples

Low GI 55 or less most fruit and vegetables (except

potatoes), whole grains, pulses,

soyabean, multi-grain bread,bran bread

Medium GI 56 - 69 sucrose, pasta, Icecream,

sheera, whole-wheat bread,

durham wheat

High GI 70 or more corn flakes, baked potato, white

rice, whitebread, watermelon,

coconut water

PULSES AND PULSE INCORPORATED


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PULSES AND PULSE-INCORPORATED

CEREAL FOODS(Chandalia et al, IJDDC, 1992)

White Bread 100 100

Wheat Gram meal 66.4 118.6

Gram Meal 48.3 202.1

Glycemic index Insulinemic index


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TREATMENT RELATED WEIGHT GAIN

IN DIABETES

Outline of talk:

1. Concept of set-point weight and settling pointweight

2. Obesity and Diabetes

3. Treatment- related weight gain

a. Conventional drugs

b. Newer drugs

4. Countering weight gain in DM and its benefits


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SET POINT vs. SETTLING POINT

Set-point Model: Individual defends preferred

level of body weight : Pre-determined and

constant environment

Settling Point Model: Individual defends a specific

body weight level within a changing environment

with constant genetic factors : environment

changes over time


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DEMOGRAPHIC DATA AND TREATMENT MODALITIES


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n Male;Female

Age (Years)

(Mean SD)

BMI(Kg/m2)

StableBody

Weight (Kg)

(Mean SD)

Duration ofDiabetes(Years)

(Mean SD)SU 108 67; 41 51.5 8.3 24.9

3.167.5 6.7 9.3 5

SU+MF 171 99; 72 51.5 7.7 27.24.3

73.5 10.1

11.6 5.5

INSULIN

89 55; 34 55.110.4

25.24.6

68.7 9.4 13.4 6.6

SU+I 85 50; 35 55.6 9.5 24.93.8

66.9 9.7 14.7 5.1

SU+MF+I

16 8; 8 57.6 6.8 27.14.9

77 12 17.8 5.6

SU : Sulfonylurea

SU + MF : Sulfonylurea + Metformin

SU + I : Sulfonylurea + Insulin

SU+MF+I : Sulfonylurea + Metformin + InsulinChandalia HB, Metabolic Syndrome & Related Disorders,2005.

WEIGHT CHANGE WITH DIFFERENT THERAPEUTIC MODALITIES


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WEIGHT CHANGE WITH DIFFERENT THERAPEUTIC MODALITIES

n InitialWeight (Kg)

(MeanSD)

Weight atStudy Point(Kg)(Mean SD)

Weight Gain(Kg)

(Mean SD)

P

SU 108 66.0 8.8 67.2 8.8 1.2 2.9 NS

SU+MF 171 72.2 13.2 72.8 13.5 0.6 2.9 NS

INSULIN 89 66.0 12.6 6 7.8 12.1 1.8 4.9 NS

SU+I 85 65.0 11.7 67.9 12 2.9 3.8


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58

60

626466

6870

72

7476

Group with Pre-

Treatment Weight

Loss (n=253)

Group without Pre-

Treatment Weight

Loss (n=216)

Stable weight

Intial weight

Post treatment

Weight

( )

PRE-TREATMENT WEIGHT LOSS AND THOSE

WITHOUT PRE-TREATMENT WEIGHT LOSS

Group with Pre-treatment

1) diabetes epidemic 2) outcome measures in diabetes 23.9.11

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