ACUTE COMPLICATIONS OF DIABETES MELLITUS

1. ACUTE COMPLICATIONS OF DIABETES MELLITUS

2. Diabetes Mellitus • Diabetes mellitus is a metabolic disorder of multiple aetiology, characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action or both (WHO 1999).

3. Physiological roles of insulin • Anabolic hormone • Enhances glucose uptake into cells of skeletal muscle and adipose tissue via receptors especially GLUT4 • Increases glycogenesis, lipogenesis and protein synthesis • Reduces glycogenolysis, gluconeogenesis and lipolysis

4. Physiological roles of insulin • In the presence of insulin deficiency; • Glucose cannot enter the cells of the skeletal muscles and adipose tissue • The cells are ‘starved’ of glucose • Glucagon acts to provide fuel • Leads to increased glycogenolysis, gluconeogenesis and lipolysis

5. Physiological roles of insulin • Substrate for gluconeogenesis include amino acids and pyruvate • Amino acids are mobilized from muscle protein breakdown • Increased lipolysis leads to production of fatty acids • These are used as substrate for ketogenesis

6. Physiological roles of insulin • Ketone bodies are used as fuel by body tissues • Hence insulinopenia manifests as a state of ‘starvation’ • There is hyperglycemia and ketonemia • Catecholamines and cortisol also help to increase hepatic glucose output and lipolysis in addition to the effects of glucagon

7. Complications of diabetes mellitus • Acute Diabetic keto-acidosis Hyperosmolar hyperglycaemic state Hypoglycaemia • Chronic Microvascular Macrovascular

8. Diabetic ketoacidosis • A diabetic emergency which occurs due to profound insulin deficiency • Occurs mainly in type1 DM • May also occur in type2 DM with poor beta cell reserve • Insulin deficiency leads to hyperglycemia and ketogenesis

9. Pathophysiology of DKA • Increased serum glucose levels occur because of increased hepatic glucose output reduced uptake by insulin-sensitive tissues • Insulin deficiency leads to lipolysis and ketogenesis due to unopposed glucagon action.

10. DKA

11. DKA • Hyperglycemia leads to increased osmolality • Polyuria occurs due to osmotic diuresis • Increased osmolality leads to fluid shifts from intracellular to extracellular space • There is increased thirst and increased water intake initially • Compensatory mechanisms fail leading to intravascular volume depletion

12. DKA • Ketogenesis leads to accumulation of ketone bodies and metabolic acidosis • The presence of unmeasured ketoacidanions causes an increased anion gap • Anion gap is calculated as; • [Na+ + K+ ] – [Cl- + HCO3-] • The major ketone bodies are acetoacetate and beta-hydroxybutyrate • Acetone is also produced in minor quantities

13. DKA • There is also increased serum osmolality • Hyperosmolality leads to cellular dehydration • In the brain this eventually leads to coma • Osmolality = 2[Na+ + K+] + Glucose/18 • Metabolic acidosis stimulates respiratory center • Leads to Kussmaul breathing (deep, laboured gasping breathing due to worsening acidosis, earlier stage in acidosis is shallow and rapid)

14. DKA • There is loss of K through; • Acidosis • Diuresis • Shift of K out of cells due to insulinopenia and hyperglycemia • Correction of acidosis and hyperglycemia leads to K shift back into the cells and subsequent hypokalemia

15. Presentation of DKA • Symptoms: • Lethargy, tiredness, non-specific abdominal pain, polyuria, nausea, vomiting, weight loss • Fast breathing, drowsiness and later coma may ensue • There may be a history of inter-current illness e.g malaria, pneumonia • In children may mimic acute abdomen

16. Presentation of DKA • Signs • Include coma, Kussmaul breathing (air hunger), acidotic breath • Note that coma is not invariable. • Dehydration, hypotension, tachycardia, cold extremities

17. Biochemical presentation • Hyperketonemia(≥ 3 mmol/L) and ketonuria (more than 2+ on standard urine sticks) • Hyperglycemia (blood glucose ≥ 11 mmol/L (~200 mg/dL). Very high levels of glucose may be recorded • Metabolic acidosis ( bicarbonate < 15 mmol/L and/or venous pH < 7.3) • Serum potassium is variable and may be falsely high • High anion gap > 12mEq/L

18. Principles of management • If in coma, Resuscitation; check ABCD • A: Airway ensure it is patent • B: Breathing check adequacy • C: Circulation set up IV access • D: Drugs; emergency drugs as needed

19. Principles of management • Replace fluid losses • Correct insulin deficiency and hyperglycemia • Replace K • Correct acidosis • Treat underlying infection • Prevent recurrence

20. Fluid replacement • Estimated fluid deficit is usually about 6 liters • Monitoring is essential to prevent over-correction • Normal saline is fluid of choice • Monitor response with central venous line, urine output (15ml/hr), clinical response

21. Fluid replacement • Use 0.9% Normal saline initially • Typical regimen of fluid replacement include • 1 litre in first 30 minutes • 1 litre over 1 hour • 1 litre over 2 hours • 1 litre over 4 hours • 1 litre over 4 hours • 1 litre over 6 hours • Fluid switch to 5% Dextrose/saline when RBG < 250mg/dl

22. Insulin and glucose • Correct hyperglycaemia with soluble insulin • Bolus IV dose of 10U • Commence infusion pump to deliver 6-10iu/hr (about 0.1U/kg/hr) • IM hourly insulin can be given in absence of pump. SC insulin inappropriate till patient can eat • Monitor rate of fall of BG about 50mg/dl hourly

23. Insulin and glucose • The insulin infusion be reduced if necessary • Increased insulin rate if BG drop is not optimal • However assess hydration • Avoid too rapid correction because of risk of cerebral edema • Avoid hypoglycemia • Monitor BG every hour • The first SC dose should overlap the infusion by at least 30 mins

24. Potassium replacement • 40 mmol of potassium chloride added to second litre of IV fluid • Ensure patient is making urine; pass a catheter • Further replacement depends on serum potassium level • K > 5.5 No replacement • 3.5 -4.5 40mmol/l of infusion • Correction of metabolic acidosis Not usually necessary

25. Other treatment • Antibiotics to treat underlying infection • Cultures • ECG monitoring • Monitor potassium • Monitor urine output • Take history and search for precipitants eg compliance etc • Counselling

26. Hyperglycemic hyperosmolar state (HHS) • Similar to DKA • Occurs in type2 patients who still have insulin reserve • Ketoacidosis is mild or absent • Very high glucose levels; may be up to 1000mg/dl • Very high osmolality; 350mosm/l or more • Severe dehydration

27. HHS • Insulin requirement is less • BG falls rapidly with rehydration • Avoid cerebral edema and cardiac decompensation with fluid replacement • 0.45% saline preferred due to hyperosmolality • Anticoagulation with heparin or enoxaparin • Treat underlying infection

28. HYPOGLYCAEMIA • Glucose is an obligate metabolic fuel for the brain • Brain cannot store glycogen • Survival requires continuous supply of glucose to the brain • Endogenous glucose is produced by glycogenolysis and gluconeogenesis mainly in the liver • Glucose tightly regulated by insulin and counter-regulatory hormones; glucagon, cortisol, adrenaline

29. Hypoglycaemia • Whipple’s triad definition; • (1) symptoms, signs, or both consistent • with hypoglycaemia; • (2) a low measured plasma glucose concentration and; • (3) resolution of those symptoms and signs after the plasma glucose concentration is raised

31. Hypoglycaemia • Falling glucose levels trigger a sequence of reactions; • 1. Fall in insulin levels occur first • 2. Increase in counter-regulatory hormones • 3. Sympatho-adrenal stimulation • 4. Cognitive decline and manifestation of brain failure i.e coma or seizure • Death may occur

32. CAUSES IN DIABETIC PATIENTS • Injudicious use of glucose lowering agents; overdose, skipped meals etc • Most common with insulin use • Oral agents include sulphonylureas, Glinides • Hypoglycaemia unawareness esp Type1 patients

33. HYPOGLYCAEMIA • Autonomic and neuroglycopenic symptoms • Sweating, hunger, anxiety, tachycardia • Confusion, drowsiness, inability to concentrate, irritability • Coma may ensue

34. Hypogycaemia: autonomic symptoms Adrenergic Cholinergic Sweating Hunger Paraesthesiae • Palpitations • Tremor • Anxiety/arousal

35. Hypoglycaemia: neuroglycopenic symptoms • Cognitive impairment • Impaired judgement • Behavioral changes • Psychomotor abnormalities • At lower glucose levels, seizure and coma

36. Hypoglycaemia • Signs include; pallor, diaphoresis, increased heart rate, increased systolic BP • Threshold recommended is <3.9mmol/l • Hypoglycemia unawareness is largely the result of reduced release of the sympathetic neurotransmitters norepinephrine and acetylcholine in patients

37. Hypoglycaemia- management • Medical emergency • If conscious and able to eat, give sugary drink or glucose tablets • IV 50ml 50% glucose • IM glucagon 1mg • Recurrence is likely in patients on long-acting insulin or sulphonylureas • These patients should be admitted for observation • Maintained on IV glucose till stable

38. Lactic acidosis • May occur in diabetic patients on biguanide therapy. • Risk is low with metformin; avoid in hepatic or renal failure • They present in severe metabolic acidosis with a large anion gap, usually without significant • hyperglycaemia or ketosis

39. Lactic acidosis • Treatment is by rehydration and infusion of isotonic 1.26% bicarbonate. The mortality is in excess of 50%.