1. Hypoglycemia Dubai February 2014 Workshop Hypoglycaemia and its management

2. Hypoglycaemia Formal definition –Blood glucose <70-mg/dl Causes –Too much insulin? –Too little food? –Unusual exercise? FOUR IS THE FLOOR

3. WHICH PATIENTS WITH HYPOGLYCAEMIA SHOULD BE ADMITTED TO HOSPITAL FROM A & E FOLLOWING HYPOGLYCAEMIC COMA? Insulin treated patients who recover quickly from hypoglycaemic coma and who are otherwise well and able to eat normally may not need to be admitted to hospital. Admission is advised for: –Any insulin treated patient who is slow to recover –Large amounts of insulin injected in error or with suicidal intent –Insulin treated patients who are drunk - alcohol may precipitate or prolong hypoglycaemia –Insulin treated patients with hypopituitarism, hypoadrenalism or chronic renal failure –Elderly patients on sulfonylureas

4. Clinical features of hypoglycaemia Adrenergic symptoms Tachycardia Palpitations Tremor Anxiety Sweating Flight or fright symptoms Neuroglycopenia Faintness Feeling of hunger Headache Abnormal behaviour Altered consciousness Eventually, coma Lack of glucose to brain

5. Hypoglycemia unawareness Autonomic:tremor, sweating, hunger, heart palpitations,anxiety. Neuroglycopenic:confusion, difficulty concentrating, blurred vision, weakness, drowsiness, irritability.

6. Fall in blood glucose COUNTER-REGULATORY MECHANISM ACTIVATED BY HYPOGLYCAEMIA Vagal stimulation Adrenal medulla stimulation Neuroglycopenia Parasympathetic Sympathetic Glucagon release Adrenaline release Stimulates glycogen breakdown in liver

7. HYPOGLYCAEMIC COMA IN DIABETIC PATIENT IMMEDIATE MANAGEMENT Hypoglycaemic reaction (‘hypo’) in a diabetic patient on insulin can result from excessive insulin dosage, excessive exercise or decreased carbohydrate intake due to missed or delayed meal. It can also occur in elderly patients due to sulfonylurea therapy Diagnosis Patient’s skin feels moist and sweaty Reflexes may be brisk with extensor plantar response Confirm with plasma glucose <3 mmol/L Treatment If conscious, sugar or sweet drinks e.g. 75g glucose or 250mls lucozade If drowsy, HYPOSTOP gel If unconscious: Glucagon* 1mg i.v., i.m. or s.c. Restores consciousness in 10-15 mins 20ml 50% dextrose i.v. Restores consciousness within 5 mins Severe hypoglyceamia with no response to glucagon or dextrose - ? cerebral oedema and/or high dose steroids e.g. 2 mg dexamethasone i.v. 4-6 hourly 200ml 20% mannitol over 20-30 mins high flow oxygen dextrose infusion 10% or 20%, 0.5 litre 2-4 hourly consider ITU for ventilation * If hypoglycaemia is precipitated or associated with excess alcohol intake, glucagon may be ineffective as alcohol blocks glycogenolytic action of glucagon

8. Hypoglycaemia: Treatment

9. Exercise Diet Insulin DiabetesEquilibrium

10. Sulphonylurea induced hypoglycaemia Sulphonylureas cause release of insulin from the pancreatic  cells Continued production of insulin without adequate carbohydrate HYPOGLYCAEMIA Check blood glucose to confirm hypoglycaemia Treatment iv dextrose May need prolonged infusion

11. 1. Nathan DM, et al. Diabetologia. 2009;52:17-306. 2. Cefalu WT. Nature. 2007;81:636-49. Glucose-lowering agents classified by risk of hypoglycaemia in type 2 diabetes Hypoglycemia High risk 1 Low risk 1,2 InsulinMetformin Sulphonylureasα-glucosidase inhibitors MeglitinidesThiazolidinediones GLP-1 receptor agonists DPP-4 inhibitors

12. 50 40 30 20 10 0 Annual prevalence of severe hypoglycemia (%) (Severe: requiring external assistance) T2DM SU T2DM < 2 yrs T2DM > 5 yrs T1DM < 5 yrs Adapted from: UK Hypoglycaemia Study Group (2007) Diabetologia; 50: 1140 Type 2 DM Sulfonylureas (n = 103) Type 2 DM <2 years insulin (85) Type 2 DM >5 years insulin (75) Type 1 DM <5 years (46) Type 1 DM >15 years (54) UK Hypoglycaemia Group Study: Frequency of Severe Hypoglycemia Error bars = 95% confidence intervals T1DM > 15 yrs

13. Holstein A et al. Exper Opin Drug Saf 2010

16. Morbidity of Hypoglycaemia in Diabetes Musculoskeletal Falls, accidents (& driving accidents) Fractures, dislocations Brain Blackouts, seizures, coma Cognitive dysfunction Psychological effects Cardiovascular Myocardial ischaemia (angina and infarction) Cardiac arrhythmias

17. Outcomes of Hypoglycaemia DeSouza CV, et al. Diabetes Care 2010; 33: 1389.

18. Cardiac function during hypoglycaemia Fisher et al (1987) Diabetologia; 30: 841 Hilsted et al (1984) Diabetologia; 26: 328

19. OTHER POINTS TO NOTE RE PATIENTS WITH HYPOGLYCAEMIC COMA Hypoglycaemia may cause hypothermia Hypoglycaemic fitting can cause vertebral and occasionally long bone fractures Watch for ‘delayed’ hypoglycaemia due to excessive exercise

20. KEY TEACHING POINTS Always consider hypoglycaemia in any person whose behaviour or conscious level is abnormal. Hypoglycaemia can present with fitting. Even close colleagues may not be aware that the patient is on insulin. Neurological signs will disappear quickly with correction of hypoglycaemia. Prolonged hypoglycaemic coma can cause irreversible neurological damage.