The New HbA1c HbA1c – DCCT (%) HbA1c – IFFC (mmol/mol)

NICE Targets HbA1c<6.5% BP<140/80 mmHg, but if kidney, eye or cerebrovascular disease <130/80 LipidsCholesterol <4.0 mmol/l, LDL <2.0mmol/l AspirinFor all over 50 yrs and BP <145/90

Benefits of 10kg weight loss in Type 2 Diabetic Fall of >30% diabetes related deaths Fall of >50% fasting glucose Fall of 10mmHg systolic BP Fall of 20mmHg diastolic BP Fall of 10% total cholesterol

Newer Agents for Glycaemic Control ThiazolidinedionesGliptins Incretin mimetics Insulins

Thiazolidinediones (pioglitazone, rosiglitazone) They improve insulin-mediated glucose disposal by enhancing the sensitivity to insulin in the liver, adipose tissue and skeletal muscle. Combination with biguanide or sulphonylurea or as triple therapy in the obese. S/E Heart Failure. Increased fracture risk. Rarely liver toxicity (monitor LFT’s before treatment, and periodically thereafter). Hypoglycaemia. GI upset. weight gain.

Incretin Effect Incretin hormones (GLP1 and GIP) produced by GI tract in response to nutrient entry. Stimulates post-prandial secretion of insulin Suppresses post-prandial secretion of glucogon (reduces gluconeogenesis) Promotes satiety and reduces appetite.

Gliptins (Sitagliptin, Vildagliptin) Inhibits the breakdown of incretins Licensed for any triple therapy. And can be used with insulin. Once daily tablet. (up to bd with vildagliptin) More effective if used early in the course of diabetes. Avoid if eGFR <50 S/E Headache. URTI. Weight neutral. There are worries that it may also inhibit the breakdown of other peptide hormones involved in the immune system.

Incretin Mimetics (Exenatide and Liraglutide) GLP 1 Analogue It interacts with a specific receptor on the beta cell. Helps weight loss Sub cut injection (as rapidly degraded in the circulation) 60 minutes before meals. BD for exenatide, OD for Liraglutide

Incretin Mimetics 2 Exenatide licensed triple therapy with sulphonylurea and metformin, Liraglutide triple therapy can also include a Glitazone. NOT licensed for monotherapy. NICE : HbA1c >7.5% and BMI > 35 in people of European decent or lower BMI (>30) if other ethnicity or weight loss would benefit other co-morbidities. eGFR avoid if <30 exenatide, <60 Liraglutide. S/E nausea very common. Hypoglycaemia more common if taken with a sulphonylurea. Acute pancreatitis.

Insulin in NIDDM Newer synthetic insulin e.g insulin glargine (Lantus), and insulin determir (Glargine) Reduced risk of hypoglycaemia due to ‘peakless’ profile Very long acting Can continue oral therapy Titrated against fasting blood sugar May ultimately need multiple injections, as for Type 1

Relevant Studies UKPDS (Glyceamic control and hypertension) DCCT (Glycaemic control) EEDIT (Glycaemic control) HOT (Hypertension) ABCD (Hypertension) ASCOT (ACEI) HOPE (ACEI) CARDS (Statins) HPS (Statins) HOT (Aspirin) although newer evidence suggests not.

Subclinical Hypothyroidism

Overt Hypothyroisim Symptomatic TSH <10 Reduced serum free or total thyroxine

Sub-clinical Hypothyroidism TSH 5-10 Normal Thyroxine levels Whether to treat is controversial EXCEPT IN PREGNANCY or trying to conceive. Risk of progression to overt is small (5% pa with antibodies, 2% pa without)

When to Treat IF SYMPTOMS trial of thyroxine for 6 months, if feel better can continue (50%). NO SYMPTOMS BUT ANTIBODIES not to treat but yearly surveillance.