In the name of GOD

1. In the name of GOD

2. Hypoglycemia in diabetic patients

4. Case1 پسر ١٠ساله اي باسابقه ٣ساله ديابت به علت تشنج دراورژانس بستري شده است درازمايشات ارسالي قندخون وي ٣٠ميلي گرم دردسي ليتر گزارش شده است. • چه عللي درايجادهيپوگليسمي وي دخيل بوده است؟ • درمان مناسب بيمارچيست؟

5. Case2 دختر٧ساله اي باسابقه ٢ساله ديابت به علت كابوسهاي شبانه وافت تحصيلي اخير به شما مراجعه كرده است .دربررسيها قندخون شبانه وي ٥٠ميلي گرم دردسي ليتر گزارش شده است . • الف:چه عللي درايجاد هيپوگليسمي وي دخيل بوده است؟ • ب:چه راهكار درماني براي وي پيشنهاد مي كنيد؟

6. Case3 • پسر٧ساله اي باسابقه اخير ابتلا به ديابت به علت ضعف وبيحالي دراورژانس بستري شده است قندخون وي ٦٠ميلي كرم دردسي ليترميباشد . • چه عللي درايجادهيپوگليسمي وي دخيل بوده است؟ • درمان مناسب بيمارچيست؟

7. Case4 • دختر 1/5ساله مبتلا به ديابت با وزن 10 كيلوگرم جهت follow up به درمانگاه غدد مراجعه كرده است. ميزان انسولين دريافتي به صورت • 3واحد NPH، 2واحدRegصبح • 2واحدرگولار ظهر • 2واحد NPH ، 2واحدReg عصر مي باشد. • HbA1C =6.5 % • با توجه به جدول زیر چه تصمیمی میگیرید؟

8. Case 4

9. Definition • Most common complication of type 1 diabetes mellitusin childhood. • Defined as blood glucose level <65 mg/dL. • Blood glucose level <70 mg/dLis the threshold for recognizing and initiating treatment . ISPAD Clinical Practice Consensus Guidelines 2014.

10. Pathophysiology • Physiologic response include release of counterregulatory hormones such as glucagon, epinephrine, cortisol, and growth hormone. • In individuals with T1DM, this response often becomes blunted over time. • The glucagonresponse is impaired . • Epinephrinesurge may be attenuated.

11. Pathophysiology • Impairment of the epinephrine response occurs in 30 percent of children whose diabetes is well controlled . • This is especially likely to occur in tightly controlled patients with frequent biochemical hypoglycemia. Diabetes Care 2009

13. Symtoms • Adrenergic: due to sympathetic neural activationand epinephrine release . • Neuroglycopenic: direct effects of hypoglycemia on theCNS. • Behavioral : consequence of adrenergicand neuroglycopenic responses ISPAD Clinical Practice Consensus Guidelines 2014.

15. Symtoms • Adrenergic : Tremor, pallor, rapid heart rate, palpitations, and diaphoresis. • Neuroglycopenic :Fatigue, lethargy, headaches, behavior changes, drowsiness,unconsciousness, seizures, or coma. • Behavioral : irritability, agitation, erratic behavior,quietnessor tantrums(most common in younger children). ISPAD Clinical Practice Consensus Guidelines 2014

16. Hypoglycemia unawareness • Lack of warning symptoms ofhypoglycemia because of blunting of the autonomic epinephrine response . • Commonly seen in children with long duration of diabetes . • Increases the risk of severe and recurrent hypoglycemia. • Any episode of hypoglycemia can lowerthe glucose threshold at which adrenergic discharge and symptoms occur. • Prevention of hypoglycemia for a few weeks can restorehypoglycemia awareness. up to date 21.3

17. Nocturnal hypoglycemia • Due to decreased release of counterregulatory hormones during sleep • Commonin children • Reported up to47 percent . • Can be subtle • Symptoms : nightmares, restless sleep, and upon awakening ,headache, confusion, or behavior changes. Up to date 21.3

18. CLASSIFICATION OF SEVERITY • Mild hypoglycemia: adrenergic and mild neuroglycopenicsymptoms. (ie,headachesand behavior changes). • Older children can recognize symptoms . • Do not need assistance of a second person. Can be treated with oral intake of a rapidly absorbed carbohydrate. up to date 21.3

19. CLASSIFICATION OF SEVERITY Mild hypoglycemia in infants : • Unable to communicate symptoms of hypoglycemia to caregivers. • May not have the same adrenergic signs as older children. Nonspecific symptoms include poor feeding, lethargy, jitteriness, and hypotonia. up to date 21.3

20. CLASSIFICATION OF SEVERITY Moderate hypoglycemia : • Neurologically impaired to a level that requireshelp from a second person to administer oral therapy. In the absence of a person to aid therapy,moderateepisodes could become severe . up to date 21.3

21. CLASSIFICATION OF SEVERITY Severe hypoglycemia: • Presence of severe neurologic symptoms(seizures or coma), OR • Requirement for intervention with SlCor IM glucagonand/or IV dextrose. up to date 21.3

22. RISK FACTORS • Age of the patient • Degree of glycemic control • Insulin regimen • Exercise • Alcohol ingestion • Timing, frequency, and carbohydrate content of meals • Acute illness • Psychological and socioeconomic factors, including patient education and self-care beha • Occurrence of prior hypoglycemic episodes

23. RISK FACTORS Age : • More common and severe in younger children . • Food intake, activity, and adherence to treatment are less predictable. • Aiming for very tight glycemic control can increase the risk .

24. Risk factors Targets for glycemic control : • ADA and International Society for Pediatric and AdolescentDiabetes (ISPAD) now recommend a general target A1C of <7.5 percent for all pediatric age groups.

25. Risk factors Insulin regimens : • Intensive insulin therapy has the advantage of improved glycemic control, and probably also reduces the risk for hypoglycemia when appropriately administered. • Conventional regimens : Patients using a fixed conventional insulin regimen are at risk for hypooglycemic events. • Insulin pump:is similar to or somewhat better than MDI in achieving glycemic control and avoiding hypoglycemic episodes.

26. stacking effect • Frequent administration of boluses of rapid-acting and short-acting insulin before the glucose loweringeffect of each dose has completely dissipated . • Devices (glucose sensors) that continuously monitor blood glucose have been used to enhance insulindosing for patients using an insulin pump; this is known as sensor-augmented pump therapy. • This approach may reduce the risk of hypoglycemia compared with standard insulin pump therapy.

27. Exercise

28. Risk factors Exercise: • Well-established cause of hypoglycemia . • Enhances insulinsensitivity. • Increases utilization of glucose. • Increases insulin absorption from the injection site dueto increased blood flow. • The hypoglycemic effects of exercise can be delayed several hours.

29. Risk factors Exercise : • Nearly all forms of activity lasting >30 min will be likely to require some adjustment to food and/ or insulin. • Continuous moderate-intensity exercise may causefall in blood glucose levels.

30. Risk factors Recommendations: • Do 2 or 3 pre-exercise glucose measurements at 30-min intervals. • Monitoring BG Q30min during exercise & Q2h after the end of exercise for up to 2 readings. • Post-exercise measurements may be needed for up to 24 hours after the end of exercise (late-onset hypoglycemia).

31. Risk factors Recommendations : • Monitoring blood glucose before, during, and after vigorous activity. • If this is a new activity,monitoringshould be done up to 12 hours after physical activity (possible delayed effects). • Consuming a snack before and/or during the time of increased activity. • Reducing the last insulin dose before activity.

32. Risk factors Alcohol ingestion : • A common trigger of hypoglycemic episodes in adolescents. • suppresses gluconeogenesis and glycogenolysis . • Acutely increases insulin sensitivity . • The combination of exercise with alcohol ingestion increases the risk for severe hypoglycemia.

33. Risk factors Acute illness : • Causes nausea, vomiting, and anorexia. • Poor oral intake . • Hyperglycemia can also occur (peripheralinsulin resistance). • Frequent blood glucose monitoring is mandatory for insulin dose adjustment .

34. Risk factors Meals : • Variations in the timing and carbohydrate content of food intake result in erratic glycemiceffects and an increased risk of hypoglycemia. • Fixed conventional insulinregimen does not match glycemic needs.

35. Risk factors Psychological and socioeconomic factors : • Lower socioeconomic status and psychiatric disorders.

36. Risk factors Coexisting autoimmune disorders : • Celiac disease, Addison’s disease, and autoimmunethyroiditis. • Recurrent unexplained hypoglycemia.

38. TREATMENT Mild and moderate hypoglycemia : • Treat orally with a concentrated and rapidly absorbed simple carbohydrate food source (10 to 15 g glucose). • Sweetened fruit juice, glucose tablets, or cake frosting. • Glucoseand sucrose are probably moreeffective than fructose in treating hypoglycemia .

39. TREATMENT • A snack with a mixed foodsource should be eaten to sustain blood glucose levels( peanut butter sandwich, bagel withcheese ). • Blood glucose should be checked again in 15 to 20 minutes . • May need to eat additional carbohydrates until blood glucose are sustainedabove 100 mg/dL.

40. TREATMENT Severe hypoglycemia : • Intervention with glucagon and/or IV dextrose. • Glucagon is administered S/C or IM: • •≤20 kg: 0.5 mg (or 0.02 to 0.03 mg/kg) • •>20 kg: 1 mg • These doses of glucagon are usually sufficient to increase blood glucose within a few minutes. • Glucagon must be followed by oral intake of concentrated carbohydrates(immediately uponawakening from the confused state). • Severe hypoglycemia and glucagon maycause nausea and vomiting within 45 minutes to an hour.

41. TREATMENT • Intravenous dextrose can be given at a dose of 0.25 gram/kg (maximum single dose 25 grams). • This is usually achieved by giving 2.5 mL/kg of 10 percent dextrose solution, or 1 mL/kg of 25 percentdextrose solution. • Every child should have a glucagonkit at home, school/daycare, and in the car during long journeys.

42. NEUROLOGIC SEQUELAE • Early onset of T1DM may be associated with an increased risk for mild neuropsychological dysfunction . • One hypothesis is that these effects are caused by severe or repeated episodes of hypoglycemia, which may have deleterious effects on brain.

43. NEUROLOGIC SEQUELAE • Current studies provide some reassurance that moderateepisodes of hypoglycemia may not beassociated with long-term cognitive sequelae in adolescents and adults . • Severe hypoglycemia clearly has short-term effects on cognitive function.

44. NEUROLOGIC SEQUELAE • Mental efficiency, attention andmemory , alter findings on the EEG, increase regional cerebral blood flow. • Acute and transient cortical blindness(severe hypoglycemia). • Stroke-like hemiparesis (persist for up to 24 hours). • Critical activities(driving or performance in standardized schoolexaminations) • Efficiency on mathematical tasks(even in mild hypoglycemia). • Death(prolonged severe hypoglycemia)

45. FEAR OF HYPOGLYCEMIA • Result in poor glycemic control. • Some children and parents who are concerned about hypoglycemia maykeep blood glucose values above targets (avoid hypoglycemic episodes ).

46. Somogyi phenomenon • should be suspected in patients presenting with atypical hyperglycemia in the early morning that resists treatment with increased insulin doses.

47. Somogyi phenomenon • Overtreatment with insulin induces hypoglycemia, thus initiating counter regulatory hormone release. • This stimulates lipolysis,gluconeogenesis, and glycogenolysis, which in turn cause rebound hyperglycemiaand ketosis.

48. Somogyi phenomenon • Test of blood glucose between 2 and 3 a.m.Lowblood glucose levels could signify the Somogyi effect is in action.

49. Somogyi phenomenon • Snack with protein before bedtime, like a piece of toast with butter, or some cheese, or yogurt, or some nuts. • Go to bed with a glucose level slightly higher than usual. • Reduce evening or bedtime insulin.

50. Somogyi phenomenon • Decrease evening long-acting insulin (NPH) dose. • Regular insulin before dinner and NPH at bedtime. • Substitution of regular insulin with an immediate-acting insulin analog, such as Human insulin lispro,may be of some help.