Diabetes Mellitus Fifth Stage-Medicine

1. Diabetes MellitusFifth Stage-Medicine Dr. Sarbast Fakhradin MBChB, MSc Diabetes Care & Management

2. Comprehensive diabetes care of type 2 DM

3. Patient education & follow up: DAFNE & DESMOND • It is essential that people with diabetes understand their disorder and learn to handle all aspects of their management & educating patients about diabetes complications. • Carry a diabetic card stating their name and address. • Driving

4. Patient education & follow up: DAFNE & DESMOND Blood glucose monitoring; Target Preprandial capillary plasma glucose (70-130 mg/dl) Target postprandial capillary plasma glucose (< 180 mg/dl) • A. Treatment with insulin; • Regular BG monitoring should be performed by all patients to adjust the insulin dose and detect hypoglycaemia • Daily pre-prandial and bedtime measurements are usually recommended

5. Treatment with oral hypoglycemic agents; • BG monitoring is optional in many patients with stable type 2 diabetes. • Monitoring is most useful in patients taking sulphonylureas, during intercurrent illness and prescription of corticosteroids, and during changes in therapy. • Lower limbs & feet • Blood pressure < 130/80 • Smoking & alcohol • Hypoglycemic episodes. • Psychological support • Target Lipid profile: Cholesterol< 200mg/dl, • LDL < 100 mg/dl, TG < 150 mg/dl HDL> 40 mg/dl.

6. Lifestyle modification • 1. Healthy diet • 2. Regular Exercise: in the form of walking, gardening, swimming or cycling, approximately 30 minutes daily, as this improves insulin sensitivity and the lipid profile and lowers blood pressure. • 3. Stop smoking • 4. Reduce/stop alcohol intake • 5. Salt: reduce sodium intake to no more than 6 g daily.

7. The glycaemic index (GI) of a carbohydrate-containing food is a measure of the change in blood glucose following its ingestion. Consumption of foods with a low GI is encouraged. • All the CHO prescribed should be taken in the form of starches and other complex sugars. • Fiber- rich foods (e.g barley, oats, legumes, beans & lentils) has been associated with improved blood glucose control & lower blood lipids in both normal, diabetic & hyperlipidemic persons. • Low-calorie and sugar-free drinks are useful for patients with diabetes. These drinks usually contain non-nutritive sweeteners. Many 'diabetic foods' contain sorbitol, are expensive and high in calories, and may cause gastrointestinal side-effects. As a result, these foods are not recommended as part of the diabetic diet.

8. Recommended composition of diet for people with diabetes: • CHO 40-65% • Fat < 35% ( saturated <10%) • Protein 10-15% • Fruit/Vegetable 5 portions daily

9. Anti-Diabetic Medications • Oral Agents: 1. Biguanides (Metformin) 2. Insulin Secretagogues – Sulphonylureas (Gliclazide) 3.Insulin Secretagogues – Non-sulphonylureas (Repaglinide) 4. DPP4 inhibitor (Sitagliptin) 5. α-glucosidase inhibitors (Acarbose) 6. Thiazolidinediones (TZDs) (Pioglitazone) • Injections: • 1. Insulin • 2. GLP-1 agonist (Incretin mimetic) Exenatide & Liraglutide

10. Biguanides (Metformin) First drug of choice for obese patients in whom strict dieting has failed to control type 2 diabetes. • Insulin sensitivity and peripheral glucose uptake are increased, • Impairs glucose absorption by the gut and inhibits hepatic gluconeogenesis • It does not increase insulin secretion and seldom causes hypoglycaemia. • Metformin is given with food.

11. Biguanides (Metformin) • Glucose-lowering effect of metformin is synergistic with that of sulphonylureas. • Improves lipid profiles & reduces risk of CA. • SE: Dyspepsia, Risk of lactic acidosis: contraindicated in patients with impaired renal or hepatic function, drinking alcohol in excess, hypoxia, & shock. • Not contraindicated in pregnancy.

12. SULPHONYLUREAS • Mainly for people with type 2 diabetes who are not overly obese. • First Generation: Tolbutamide (well tolerated, short acting, useful in elderly), Chlorpropamide Very long acting (up to 60 hours), avoid in elderly. • Second generation: Glibenclamide, Gliclazide, Glimepiride, Glipizide. • Glibenclamide is prone to induce severe hypoglycaemia (avoid in the elderly) • Principally stimulate production of insulin, may reduce glucagon levels.

13. SULPHONYLUREAS • SUs can cause hypoglycaemia and their use should therefore be closely monitored in the elderly & in those with nephropathy. • Several drugs can potentiate their hypoglycaemic effect (e.g. salicylates, phenylbutazone and antifungal agents) • SE: Hypoglycemia, increased appetite and weight gain, skin rashes (hypersensitivity) and G.I. Disturbances, cholestatic Jaundice, blood dyscrasia. Feature of disulfiram- like reaction occur in some patients after taking alcohol. • Occasionally chlorpropamide can induce (SIADH).

14. Meglitinides - prandial glucose regulators • Repaglinide, Nateglinide • Stimulates insulin release (rapid and short acting) • Better control of postprandial hyperglycaemia • Take before meals. • It is less likely to cause hypoglycaemia than sulphonylureas.

15. Alpha-glucosidase inhibitors (Acarbose) • Carbohydrate digestion in the small intestine is slowed down by selectively inhibiting disaccharidases • Glucose is not absorbed into the bloodstream so quickly. • SE: Bloating, flatulence, diarrhoea and abdominal pain, especially upon initial treatment.

16. Thiazolidinediones (pioglitazone) • Bind and activate peroxisome proliferator-activated receptor-γ (PPARγ agonists). • Reduced insulin resistance and decreased insulin levels • insulin concentrations are not increased & hypoglycemia is not a problem. • Fat redistribute from the abdominal stores and into subcutaneous depots. However, body weight and total body fat are increased. • Pioglitazone may reduce myocardial infarctions and strokes (improvement in endothelial function), but increase the risk of HF?

17. Thiazolidinediones (pioglitazone) • SE: sodium and fluid retention, which is aggravated if they are combined with insulin, upper limb fractures. • TZDs must be avoided in patients with cardiac failure, hepatic impairment or severe renal insufficiency. • Increase LDL (non-atherogenic form?), increased HDL, lowered FFA, lowered triglycerides.

18. Oral hypoglycaemics -glucosidase inhibitors Sulfonylureas/meglitinides  Rate of carbohydrate breakdown/absorption  Insulin secretion Biguanides Thiazolidinediones  Insulin resistance  Glucoseoutput  Insulin resistance

19. Mechanisms of glucose-stimulated insulin secretion

20. Incretin-based therapies • The secretion of insulin in response to a rise in blood glucose is greater when glucose is given by mouth than by intravenous infusion. In part this is caused by secretion of gut hormones, or incretins (Glucagon-like peptide (GLP-1), which potentiate glucose-induced insulin secretion. • GLP-1 suppresses glucagon secretion, delays gastric emptying, reduces appetite and encourages weight loss.

21. Incretin-based therapies (Cont.) • They improve postprandial glucose excursions and early satiety • GLP-1 is rapidly degraded by the enzyme, dipeptidyl peptidase 4, inhibitors of this enzyme can be used to prolong its biological effect. • The DPP-4 inhibitors or gliptins (sitagliptin, vildagliptin and saxagliptin) are oral agents which act in this manner.

22. Incretin-based therapies (Cont.) • Exenatide & Liraglutide (SC injection) are Synthetic GLP-1 receptor antagonists with longer therapeutic action. They induce weight loss in most patients. SE: pancreatitis & GI disturbance. • Incretin-based therapies are most useful in obese patients and can be used in combination with other oral anti-diabetic agents.

23. Insulin • Insulin are either bovine or porcine, human insulin produced by recombinant DNA technology & protein engineering technique. • In most countries, the insulin concentration in available formulations has been standardised at 100 U/mL. • Plastic Syringe or pen injector. • Insulin is usually given by the SC route, IV or IM routes. • Rotation of injection sites is recommended to reduce insulin injection site damage.

24. Insulin (Cont.) • It is removed mainly by the liver and also the kidneys; plasma insulin concentrations are elevated in patients with liver disease or renal failure. • Absorption from the abdomen is faster than from thighs or upper arms and may be preferred for short- acting preparation. • Insulin absorption may be influenced by insulin formulation, injection site, depth and volume of injection, skin temperature (warming), local massage and exercise.

25. Types of insulin • Rapid-acting insulin– it begins to work about 5 minutes after injection, peaks in around 1 hour, and continue to work for 2-4 hours (Lispro, Aspart). • Regular or Short-acting insulin – reach the bloodstream within 30 minutes after injection. It will peak anywhere from 2-3 hours after injection and will stay effective for around 3-6 hours. • Intermediate-acting insulin (NPH)- reach the bloodstream within 2-4 hours after injection. It will stay effective for around 12-18 hours. • Long-acting insulin (Glargin)this type of insulin will reach the bloodstream within 6-10 hours after injection and will stay effective for 20-27 hours. • Premixed insulin

26. Insulin • Side-effects: • Hypoglycaemia • Weight gain • Peripheral oedema (insulin treatment causes salt and water retention in the short term) • Insulin antibodies (animal insulins) • Local allergy (rare) • Lipodystrophy at injection sites

27. Insulin dosing regimens • Most people require two or more injections of insulin daily. • Once-daily injections rarely achieve satisfactory glycaemic control & are reserved either for some elderly patients or for those who retain substantial endogenous insulin secretion & have a low insulin requirement. • Twice- daily mixtures of short- and intermediate acting insulin is a commonly used regimen. • Basal-Bolus: A regimen of multiple injection of short- acting insulin before the main meals, with an appropriate dose of single daily intermediate- or long acting insulin. • The dose of the insulin preparations is adjusted according to frequent monitoring of blood glucose levels. Blood glucose monitory should be intensified during intercurrent illness & other stressful conditions (Sick Day rule)

28. Combined oral anti-diabetic therapy and insulin • In patients with type 2 diabetes who are requiring increasing doses of oral anti-diabetic drugs, the introduction of a single dose of an intermediate- (e.g. isophane) or long-acting insulin analogue, administered at bedtime, may improve glycaemic control and delay the development of overt pancreatic β-cell failure. • Insulin Pump • Transplantation • Surgery

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