Diabetes Mellitus

Diabetes Mellitus

• 1.
  Diabetes Mellitus
• 2.
  Glucose metabolism • Normallevel: 3.5–8.0 mmol/L (63–144 mg/dL) • Liver absorbs/stores glucose in the postabsorptive state and releases it into the circulation between meals to match the rate of glucose utilization by peripheral tissues. • Liver combines 3-carbon molecules derived from breakdown of fat, muscle glycogen (lactate) and protein into the 6-carbon glucose molecule by the process of gluconeogenesis. • Insulin is involved in storage of glycogen in liver and muscle, and triglyceride in fat. • During meal: insulin is released from pancreas into the portal vein and facilitates glucose uptake by fat and muscle and suppresses glucose production by the liver. • Fasting state: insulin are low and modulates glucose production from the liver • Counter-regulatory hormones: glucagon, adrenaline, cortisol and GH: opposes insulin and cause production of glucose from the liver and less utilization of glucose in fat and muscle for a given plasma level of insulin.
• 5.
  Cause Type 1 diabetesmellitus: • due to an autoimmune destruction of the pancreatic β cells. • occurs in genetically susceptible individuals and is triggered by environmental antigens • Autoantibodies against insulin and islet cell antigens (e.g. glutamic acid decarboxylase) predate the onset of clinical disease by several years. • It is an association with other organ-specific autoimmune diseases (autoimmune thyroid disease, Addison’s disease and pernicious anaemia)
• 6.
  Cause Type 2 DM •genetic causes of type 2 DM include: >mutations of the insulin receptor > structural alterations of the insulin molecule • Environmental factors: central obesity: trigger DM in susceptible individuals • β-cell mass is reduced to 50% at time of DX • Hyperglycemia: result of reduced insulin secretion and peripheral insulin resistance
• 7.
  Clinical features Acute presentation: •Young pt: 2– 6week hx: thirst, polyuria and wt loss • Polyuria is due to osmotic diuresis, blood glucose exceed renal tubular reabsorptive capacity • Fluid and electrolyte losses stimulate thirst. • Wt loss is due to fluid depletion and breakdown of fat and muscle secondary to insulin deficiency. • Ketoacidosis: if early sx are not recognized and treated. Subacute presentation: • Older patients may present with the same symptoms, although less marked and extending over several months. • may also complain of lack of energy, visual problems and pruritus vulvae or balanitis due to Candida infection.
• 8.
  Diagnosis if any oneof the following is present: • Casual plasma glucose ≥11.1 mmol/l • Fasting plasma glucose ≥7.0 mmol/l • 2-hour postprandial plasma glucose ≥11.1 mmol/l
• 11.
  Treatment Biguanide • Metformin isa biguanide • it reduces glucose production by the liver and sensitizes target tissues to insulin. • It is the first line treatment in patients who have not achieved optimal glucose control with diet alone, in overweight patients • It reduces cardiovascular risk in diabetics.
• 12.
  • Metformin: canbe used in combination tx when single agent has failed to control DM Side-effects: • anorexia and diarrhoea • Lactic acidosis in pts with severe heart failure, liver disease or renal disease (serum creatinine > 150 μmol/L), in whom its use is contraindicated.
• 13.
  Sulphonylureas: promote insulinsecretion. • Glibenclamide is best avoided in elderly people and in those with renal failure because of its relatively long duration of action (12–20 hours) and renal excretion. • Tolbutamide, which is shorter acting and metabolized by the liver, is a better choice in older pts • The most common side-effect of sulphonylureas is hypoglycaemia, which may be prolonged. • Meglitinides, e.g. repaglinide and nateglinide, are also insulin secretagogues. • They have a rapid onset of action and short duration of action and are administered shortly before each main meal.
• 14.
  Acarbose: inhibits intestinalα-glucosidases and impairs carbohydrate digestion and slows glucose absorption. • Postprandial glucose peaks are reduced. • Gastrointestinal side-effects, e.g. flatulence, bloating and diarrhoea, are common and limit the dose and acceptability of this treatment.
• 15.
  • Weight lossis associated with improved diabetic control and even remission of diabetes. • Orlistat is an intestinal lipase inhibitor and reduces the absorption of fat from the diet. • It promotes weight loss in patients under careful dietary supervision on a low fat diet. • Gastric banding and gastric bypass surgery should be offered to those with marked obesity unresponsive to 6 months intensive attempts at dieting and graded exercise.
• 16.
  main types ofinsulin: 1. Short-acting (soluble) insulins: • start working within 30–60 minutes andlast for 4–6 hours. • They are given 15–30 minutes before meals in patients on multiple dose regimens 2. Short-acting insulin analogues • human insulin analogues (insulin aspart, insulin lispro, insulin glulisine) have a faster onset and shorter duration of action than soluble insulin but overall do not improve diabetic control. • They have a reduced carry-over effect compared to soluble insulin and are used with the evening meal in patients who are prone to nocturnal hypoglycaemia.
• 17.
  3. Longer-acting insulins. •Insulins premixed with retarding agents (either protamine or zinc) precipitate crystals of varying size according to the conditions employed • These insulins are intermediate (12–24 hours) or long acting (more than 24 hours). • The protamine insulins are also known as isophane or NPH insulins • zinc insulins as lente insulins • Insulin glargine is a structurally modified insulin that precipitates in tissues and is then slowly released from the injection site.
• 18.
  • Thank yougoogle… • Harrisons • WHO guideline http://crisbertcualteros.page.tl