1. Hypoglycemia Rami Unterman, MD

2. Hypoglycaemia Medical emergencies in diabetes mellitus Diabetic KetoAcidosis (DKA) Hyperosmolar Hyperglycemic State (HHS) Hypoglycemia High Glucose Low Glucose

3. Hypoglycaemia Definition of hypoglycaemia When the level of glucose falls in the blood so that the cells in the periphery, and eventually the brain cells, do not get adequate glucose to function.

4. Hypoglycaemia Hypoglycemia – Whipple’s triad: Symptoms Low blood glucose Relief of symptoms when blood glucose raised

5. Hypoglycaemia Physiology of hypoglycemia

6. Hypoglycaemia Causes of hypoglycemia

7. Hypoglycaemia Were it not for hypoglycemia, diabetes would be rather easy to treat… Increasing efforts to achieve glycemic control Increasing episodes of hypoglycemia

8. Hypoglycaemia The body’s response ●Endogenous insulin secretion suppressed (<80 mg/dl) Release of counter-regulatory hormones: glucagon, epinephrine, cortisol, growth hormone (<65 mg/dl) Autonomic (adrenergic) response (<55 mg/dl) –Tremors in 32%-78% of people –Palpitations in 8%-62% –Sweating in 47%-84% –Anxiety in 10%-44% –Ravenous hunger in 39%-49% –Nausea in 5%-20% –Tingling especially around lips in 10%-39%.

9. Hypoglycaemia The body’s response At about 45-50 mg/dl: -Neuroglycopenia- brain lacks glucose -Temporary cognitive impairment -prolonged neuroglycopenia can cause permanent brain damage and eventually death Symptoms: Difficulty concentrating (31%-75%) Confusion (13%-53%) Weakness (28%-71%) Drowsiness (16%-33%) Vision changes (24%-60%) Headache (24%-36%) Tiredness (38%-46%) coma Wide variation in symptoms and thresholds

10. Hypoglycaemia Glucagon- most important Hypoglycemia stimulates release It acts in the liver to increase glucose production –glycogenolysis –gluconeogenesis –stimulating production of ketones

11. Hypoglycaemia Epinephrine glycogenolysis gluconeogenesis Reduces cellular uptake of glucose Reduces production of insulin

12. Hypoglycaemia Cortisol and growth hormone Reduce cellular uptake of glucose gluconeogenesis Lypolysis -Energy for organs (other than the brain) -Substrates for gluconeogenesis

13. Hypoglycaemia Symptoms of hypoglycaemia MildModerateSevere Capable of self- treating May require prompting Not capable of self- treatment Tremors, palpitation, sweating, hunger, fatigue Headache, mood changes, low attentiveness Conscious or unconscious AdrenergicNeuroglycopenic

14. Hypoglycaemia Consequences of hypoglycaemia Mild-moderate –fear –anxiety –affects self- care –social stigma –prejudice Severe –injury –seizures –transient paralysis –cognitive impairment –death

15. Hypoglycaemia People at risk of hypoglycaemia people taking glucose-lowering medicines or insulin Increased risk: –too little or wrong type of carbohydrate –late or missed meal –fasting or malnourishment –too much insulin or insulin secretagogues –prolonged or unplanned activity

16. Hypoglycaemia People at risk of hypoglycaemia Increased risk: Recent severe hypoglycaemia Gastroparesis Liver disease or kidney failure Pregnancy Injection-related Over-correction of high BGL

17. Hypoglycaemia Management Mild or moderate Test if possible 15 g glucose; re-test Glucose tablets Fruit juice Soft drink Sugar Re-treat if level remains low CDA 2003

18. Hypoglycaemia Management Severe 20 g glucose Glucagon Intravenous dextrose Manage seizure – place person on their side if not too agitated

19. Hypoglycaemia Glucagon/IV dextrose options If unable to treat orally: Glucagon subcutaneously or intramuscular –1 ml for adult (0.5ml for child) –blood glucose 3.0 to 11.8 in 45 min –vomiting –severe headache IV dextrose 50%: –25-50 ml IV over 2-3 minutes –immediate response –Caution: tissue necrosis if not IV! Follow by dextrose 5% or 10% constant infusion

20. Hypoglycaemia Follow-up management Carbohydrate Consider reducing insulin Assess cause Prevent recurrence Avoid BGLs < 4 mM (75 mg/dl) If BGL < 7mM before bed, eat a snack CDA, 2003

21. Hypoglycaemia Other management strategies Long acting insulin –Glargine/levemir insulin –No peak Pump Different injection sites Depth of injection –More rapid absorption from IM than SC

22. Hypoglycaemia Relative hypoglycaemia Symptoms of hypoglycaemia without low blood glucose levels Associated with: – suboptimal control of BGL – significant and sudden change in blood glucose

23. Hypoglycaemia Rebound hyperglycaemia After nocturnal hypoglycaemia Low levels in early hours Fasting ketones may be present in prolonged hypoglycaemia Caution not to increase insulin administration!

24. Hypoglycaemia Rebound hypoglycaemia Treatment options Decrease evening intermediate- acting insulin Intermediate insulin at bedtime Long-acting insulin analogue Increase bedtime snack

25. Hypoglycaemia Defective counter-regulation hypoglycemia unawareness Defective counter-regulation and hypoglycemia unawareness Glucagon response often lost after five years with type 1 diabetes Epinephrine response may be blunted and delayed Adrenergic symptoms blunted Reliance on recognizing neuroglycopenic symptoms

26. Hypoglycaemia Managing hypoglycemic unawareness Unawareness is reversible (but requires >2 weeks of avoidance of hypoglycemia) Encourage hypoglycaemia-free state Test glucose before potentially hazardous behaviour (e.g. driving)

27. Hypoglycaemia Alcohol Increased risk of hypoglycaemia Decreased gluconeogenesis Glycogenolysis not effected –However alcoholics may have low glycogen reserves d/t low intake Decreased ability to recognize symptoms ‘Safe’ drinking education Turner 2001

28. Hypoglycaemia Hypoglycaemia in older people Risk of injury from falls May be missed or mistaken for dementia Malnutrition may increase risk of hypoglycaemia Avoid long-acting sulphonylureas in older people

29. Hypoglycaemia Summary Hypoglycaemia Common Frightening for person with diabetes and family Can usually be prevented Reduced through education, self- monitoring and self-care Must be addressed at every visit to healthcare professional Treatment must be revised if recurrent

30. Hypoglycaemia Review question 1.Which of the following symptoms are part of the autonomic response to hypoglycaemia? a.Trembling, palpitations, drowsiness b.Hunger, sweating, confusion c.Palpitations, sweating, drowsiness d.Palpitations, trembling, hunger

31. Hypoglycaemia Review question 2. Hypoglycaemia unawareness is thought to be caused by impaired counter-regulation due to: a.Repeated hypoglycaemia b.Autonomic neuropathy c.Nephropathy d.Absent glucagon production

32. Hypoglycaemia Review question 3. At what blood glucose level do neuroglycopenic symptoms generally begin to show? a.Less than 3.7mmol/L (66mg/dL) b.Less than 3.1mmol/L (56mg/dL) c.Less than 2.5mmol/L (45mg/dL) d.Less than 2.0mmol/L (36mg/dL)

33. Hypoglycaemia Review question 4. Glucagon secretion results in: a.Increased production of glucose in the liver b.Increased sensitivity to glucose in the cells c.Decreased absorption of glucose from the gastrointestinal tract d.Decrease in glucose passed in the urine

34. Hypoglycaemia Review question 5. Which would be the most appropriate to treat mild-to-moderate hypoglycaemia? a.Cup of tea b.Chocolate bar c.Six crackers d.Glass of fruit juice

35. Hypoglycaemia Answers 1. d 2. a 3. c 4. a 5. d