Michael MansfieldDiabetes ConsultantLeeds Teaching Hospitals

New units for HbA1cDiabetes is relevant to in-patient careNHS diabetes resourceGliptins & GLP-1 analogs & SGLT-2 inhibitorsEnd of lifeSodium

type 1 diabetestype 2 diabetesgestational diabetesdiabetes secondary to pancreatic diseaseunknown / uncleargenetic diabetesother

MODY 3Mutations of the hepatocyte nuclear factor 1α gene Disordered insulin releaseAutosomal dominant pedigree over 2, ideally 3 generationsAge of onset < 25 years in at least one family member No need for insulin (or detectable C-peptide) in first 2-5 years after diagnosisProgressive rise in glucose levels through lifeLow renal threshold for glucoseOften very sensitive to sulphonylurea therapy

Permanent neonatal diabetes mellitusActivating mutations of the KCNJ11 gene, which codes for the Kir6.2 subunit of the beta cell K-ATP channel.Congenital impairment of insulin releaseMostly new mutationsOnset in first 3 (- 6) months of life but no immune markers of type 1 diabetes Often responds well to sulphonylurea therapy

New units for glycated haemoglobin

DCCTHbA1c

%

IFCCHbA1c

mmol/mol

6.0 42

6.5 48

7.0 53

7.5 59

8.0 64

9.0 75

Umpierrez et al JCEM 2002, Memphis, Tennessee and Atlanta Georgia

Baker et al Thorax 2006 St George’s Hospital London

The Think Glucose programme provides a package of tried and tested products, learning and support to improve awareness and remove the obstacles to the treatment of patients with diabetes as a secondary diagnosis.

Implementing a clinical pathway will improve the patient experience and the quality of their care.

Training of staff

Links to and alerting of diabetes team

New and NHS-wide documentation

Importance of careful medicines reconciliation

IV insulin infusion safetycannulaIV fluid

Insulin storage and insulin syringes

National or local guidelines for:DKA, HHS hypoglycaemiasurgery, endoscopyhyperkalaemiaend of lifetube feedinglaboursteroids for fetal lung maturation

Capillary glucose monitoring and recording

Patient self-management/admin of insulin

“Sliding scales” and other insulin prescribing

www.diabetes.nhs.uk

withdrawn

withdrawnwithdrawn

SGLT-2 inhibitors oral 2012

(USA)

The incretin effect

oral glucose

IV glucose

oral glucose

IV glucose

Increased insulin releaseReduced glucagon release

Slowed gastric emptying

Site of GLP-1 synthesisSecretion increased after meals

Satiety effectreduced food intake

Increased glucose uptake& glycogenesis

Overview of GLP-1 physiology

DPP4 inhibitors

NICE 2009

The problem with…..Metformin is bowel side effects, risk of lactic acidosis when eGFR decreased

Sulphonylureas weight gain and risk of hypoglycaemia

Insulin is weight gain, risk of hypoglycaemia, some driving restrictionsinjections

Glitazones take weeks to start working, expensive, very marked weight gain, fluid retention and heart failure, distal bone fracture risk

Gliptins (DPP4 inhibitors) expensive, no long-term safety recordweak pancreatitis signal

Exenatide expensive, nausea and vomiting in first monthsinjected, no long-term safety record, pancreatitis signal

Liraglutide even more expensive, nausea and vomiting in first monthsinjected, no long-term safety recordpancreatitis signal, v weak thyroid malignancy signal

Dapaglifozin expensive, genital thrush, no long-term safety record

glucose control in diabetes at the end of life

altered nutritionnegative energy balanceweight reductionreduction in physical activity

systemic humoral stress response

pancreatic destructionrenal impairment

liver destructionloss of fat and muscle

steroids

psychological stressmental illness

July 2012

Key principles

Aims for glucose levels:

1.No glucose level less than 6 mmol/L2.No glucose level higher than about 15 mmol/L

Breaks down care in to 4 scenarios:

1.End of life but prognosis of more than 1 year2.Prognosis in months3.Prognosis in weeks4.Prognosis in days

A few words on hyponatraemia

Always check for hyperglycaemia:For every 3.5 mmol/L the glucose is high, sodium falls by 1 mmol/L

It’s all about the brain

Always look for timescale of sodium fallBrain tolerates slow changes (up or down) remarkably well

SIADH is not the only cause, dehydration is common too

Assessment of patient’s circulating volume status is key

A cause for appropriate ADH release/activity excludes SIADH

If patient has been on steroids then suppressed HPA axis possible

Low circulating volume (NB intact thirst)acute medical emergency including sepsissurgical abdomenhypoadrenalism (Addisons or suppressed HPA axis)diuretics

ascitesnephrosiscongestive cardiac failure

Normal or increased circulating volumesyndromes of inappropriate ADH activity (secretion or receptor)sick cell syndrome

Redistribution of body waterhyperglycaemia

Management

Usually not urgent unless the cause itself is emergencyTreatment obviously depends on the causeIn practice it often seems to self correct

May need treatment anyway if brain function impaired by sudden and/or severe fall:

ie neurological signs / seizures / reduced GCS

IV saline and in some exceptional circumstances hypertonic saline appropriate. Aim for slow improvement in Na 5mmol/L in 12 hours.Not much improvement needed to reverse brain dysfunction

Read this article: Adrogue 2000 NEJM 342: 1851