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Diabetes
- 1. Type 1 Diabetes Karen S. Penko, MD Fellow, Pediatric Endocrinology September 2005
- 2. PREP Content Specifications • Recognize signs/symptoms • Know how to treat type 1 diabetes • Know the value of hemoglobin A1c • Know the natural history • Counsel patients on self-management • Differentiate Somogyi & dawn phenomena
- 3. PREP Content Specifications • Know how to manage sick days • Know the long-term complications • Know importance of blood glucose control in preventing long-term complications • Recognize the association with other autoimmune disorders
- 4. Gary Hall Jr. Olympic swimming medalist Type 1 diabetes
- 5. Case 1 • 18 y/o white male, father pages on-call peds endo: – Polyuria, polydipsia x 1 week – 16 y/o brother has type 1 diabetes – Using brother’s supplies, BG “high”, large urine ketones – What should we do? • Leaving for college next week
- 6. At WRAMC ED Serum glucose Venous pH Bicarb UA Serum acetone Electrolytes 497 mg/dl 7.396 27 mmol/l 150 mg/dl ketones, + glucose Negative Na 133, K 4.2, Cl 94, BUN 14, creat 0.8
- 7. Diagnostic Criteria • Symptoms of diabetes and a casual plasma glucose 200 mg/dl, OR • Fasting plasma glucose 126 mg/dl, OR • 2-hour plasma glucose 200 mg/dl during an oral glucose tolerance test. • In the absence of unequivocal hyperglycemia, these criteria should be confirmed by repeat testing on a different day.
- 8. Presenting Signs/Symptoms • Polyuria, Polydipsia • Nocternal enuresis • Polyphagia • Weight loss • Fatigue, weakness • Blurry vision • Ketoacidosis: abdominal pain, nausea, vomiting, mental status changes
- 9. Epidemiology • Prevalence 1:300 • Peak age of diagnosis: 11-13 y/o • Risk for sibling: 6% • Risk for monozygotic twin: 50% • Risk for offspring: 2-10%, higher side if father has diabetes • Highest incidence: Finland, Sardinia
- 10. Pathophysiology • Autoimmune destruction of pancreatic - cell • Antibodies: – Islet cell – Insulin – Anti-glutamic acid decarboxylase 65 • T-cell mediated • Lymphocytic infiltration
- 11. Pathophysiology • Genetic susceptibility – Association with HLA DR3/4, DQ 2/8 alleles • Environmental triggers – Viruses: congenital rubella, coxsackievirus, enterovirus, mumps – Early exposure to cow’s milk
- 12. Progression to Type 1 DM Autoimmune destruction “Diabetes threshold” Honeymoon 100% Islet loss Autoimmune markers (ICA, IAA, GAD) Islet Cell Mass
- 13. Associated Autoimmune Disorders • Thyroid (Hashimoto’s, Graves’): 5-10% • Celiac Disease: 6% • Addison’s disease: <1%
- 14. Nicole Johnson Miss America 1999 Type 1 diabetes
- 15. Management • Diabetes team • Insulin • Diet • Exercise • Psychological support
- 16. Banting and Best 1923 Nobel Prize for discovery and use of insulin in the treatment of IDDM
- 17. Patient J.L., December 15, 1922 February 15, 1923 The Miracle of Insulin
- 18. Insulin Preparations - US • Novo Nordisk – NovoLog (aspart) – NovoLog Mix 70/30 – Novolin R – Novolin N – Novolin 70/30 • Sanofi-Aventis – Lantus (glargine) • Lilly – Humalog (lispro) – Humalog Mix 75/25 – Humulin R – Humulin N – Humulin 70/30 – Humulin 50/50 • Lente, Ultralente have been discontinued
- 19. Treatment with Insulin • Total daily requirement: – 0.5-1 unit/kg/day – 1.5 units/kg/day during puberty • Typical Regimens – NPH and Regular – Basal/Bolus: glargine and Novolog/Humalog
- 20. Insulin Delivery • Vials and syringes • Pens • Insulin pump
- 21. 4:00 25 50 75 8:00 12:00 16:00 20:00 24:00 4:00 Breakfast Lunch Dinner Plasma insulin ( µ U/ml) Time 8:00 Physiological Serum Insulin Secretion Profile Dawn phenomenon
- 22. 4:00 25 50 75 8:00 12:00 16:00 20:00 24:00 4:00 Breakfast Lunch Dinner Plasma insulin ( µ U/ml) Time 8:00 NPH and Regular R R N N
- 23. AM 2/3 PM 1/3 2/3 NPH 1/3 Regular ½ NPH (2/3) ½ Regular (1/3) NPH and Regular
- 24. NPH and Regular • Regular insulin given 30 min prior to a meal • NPH dose often given at bedtime • Prescribed amount of carbs at meals/snacks
- 25. NPH and Regular • AM blood glucoses → Evening NPH • Lunch → AM Regular • Dinner → AM NPH • Bedtime → PM Regular
- 26. 4:00 16:00 20:00 24:00 4:00 Breakfast Lunch Dinner 8:00 12:00 8:00 Time Glargine Lispro Lispro Lispro Aspart Aspart Aspart or or or Plasma insulin Basal/Bolus
- 27. Basal/Bolus • Basal: glargine, 50% total daily dose • Bolus: NovoLog or Humalog – Insulin to carbohydrate ratio – Correction BG – target Correction factor
- 28. Basal/Bolus • I:CHO = 450/total daily insulin dose = amount of carbs 1 units will cover • Correction Factor: “1700 rule” = 1700/TDD • Glargine can not be mixed with any other insulins
- 29. Basal/Bolus • Glargine dose limited by which blood sugar? – 2 AM and breakfast • Which blood sugar is affected by the I:CHO ratio? – 2 hour post-prandial
- 30. NPH and Regular • Advantages – 2-3 shots per day – “Easier” – less carb counting and calculations • Disadvantages – Strict dietary plan – Less flexible – Less physiologic
- 31. Basal/Bolus • Advantages – More physiologic – More flexible – Less hypoglycemia • Disadvantages – More labor-intensive (CHO counting, insulin calculations) – At least 4 injections per day
- 32. Diet • Healthy, balanced diet – 50-60% total calories from carbohydrate – <30% fat – 10-20% protein • Carbohydrate counting • No forbidden foods - moderation • Eating too much will not cause ketosis
- 33. Exercise • Increases sensitivity to insulin • Helps control blood sugar • Lowers cardiovascular risk • Blood sugar usually decreases but may initially increase • Hypoglycemia may occur during, immediately after, or 8-24 hours later
- 34. Exercise • Check blood sugar before, during, after • Always have snacks available • May need extra snacks or decreased insulin (learn from experience) – Usually 15 gm CHO for every 30 min vigorous exercise • Do not exercise if ketones are present
- 35. Psychosocial Support • Every newly diagnosed family should meet with a psychologist • Guilt • Anger • Fear • Denial • Depression
- 36. Case 1: Special Concerns for College Students • Independence • Dining hall food • Alcohol – lowers blood sugar • Roommate aware of diabetes, glucagon • Airline travel – prescription labels
- 37. Case 1 • Discharged after teaching complete on – Glargine and Humalog – 0.7 units/kg/day • 3 weeks after diagnosis blood sugars begin going low • What is going on?
- 38. Honeymoon Phase • Educate that it may happen • Diabetes is not cured! • Occurs within first 3 months of diagnosis • Insulin requirements <0.5 units/kg/day • Lasts weeks to up to 2 years • Resolution of glucotoxicity, recovery of residual β-cell function
- 39. Case 1 • Blood glucoses continue to be so low that pt takes himself off all insulin • Normal blood glucoses for 5 months off insulin • Blood glucoses begin to rise • Homesickness • Depression
- 40. Long Term Complications • Retinopathy • Nephropathy • Neuropathy • Cardiovascular disease • Prevention by optimal glucose control
- 41. Diabetes Control and Complications Trial Conventional Therapy • 1-2 injections/day • Mean A1c 9% Intensive Therapy • ≥3 injections/day • Mean A1c 7% • 1983-1993, early termination given results • Intensive therapy delays onset and progression of long-term complications in type 1 diabetes
- 42. Diabetes Control and Complications Trial • Intensive therapy reduced risk by: – 76% for retinopathy – 54% for nephropathy – 69% for neuropathy – 41% for macrovascular disease • Adverse events – Hypoglycemia – Weight gain
- 43. Case 1 – Follow-up visit • Home from college on break • Insulin requirement 0.5 units/kg/day • Physical exam • Monitoring for complications
- 44. Physical Exam • Height, weight, BP • Pubertal progression • Thyroid • Abdomen • Shot sites - lipohypertrophy • Feet • Medical alert tag
- 46. Prayer Sign Limited joint mobility Associated with: poor control, increased risk of retinopathy, nephropathy
- 47. Monitoring • Hemoglobin A1c – every 3 months • Celiac screen – at diagnosis and if ssx • Annually – TSH – Ophthalmology exam - after 10 and 3-5 yrs disease – Urine microalbumin - after 10 and 5 yrs disease – Lipid panel - puberty, unless fam hx, q5 years if normal – Influenza vaccine
- 48. Case 1 • Hemoglobin A1c - 6.0% • Ophthalmology exam – no retinopathy • TSH, FT4 – normal • Lipids – cholesterol 143 • Urine microalbumin - negative
- 49. Hemoglobin A1c • Reflects blood glucose over the past 3 months • Goal <7 for adults <7.5% for teens <8% for 6-12 y/o 7.5-8.5% for <6 y/o A1C BG 6 135 7 170 8 205 9 240 10 275 11 310 12 345
- 50. Case 1 • 1 year after diagnosis, remains diligent about sending blood sugars • Insulin requirements 0.5 units/kg/day • A1c 5.9% • Interested in the insulin pump
- 52. Insulin Pump Candidates • Highly motivated • Willing to perform frequent blood glucose monitoring • Good control on basal/bolus regimen • Proficient at carbohydrate counting • Proficient at adjusting insulin doses with I:CHO and correction factor
- 53. Insulin Pump • Only NovoLog or Humalog insulin • Hourly basal rate: 1. 80% of total daily insulin dose 2. Divided by 2 3. Divide by 24 • Same I:CHO and correction factor
- 54. Insulin Pump • Advantages – Mimics physiologic pancreatic secretion – Lifestyle – Accurate dosing – Less hypoglycemia • Disadvantages – No depot to protect from DKA – Labor intensive – Expensive
- 55. Jason Johnson Detroit Tigers Pitcher Type 1 diabetes diagnosed age 11 Wears insulin pump on field
- 56. Case 2 • 9 y/o male with type 1 diabetes for 4 years • NPH and Regular insulin 2 shots per day • Total insulin dose = 0.8 units/kg/day • Relatively high AM numbers
- 57. Case 2 B L D HS 200 110 106 120 220 97 102 115 198 105 132 110 241 99 96 122
- 58. Case 2 • What is going on? • What additional information do you want? • 2AM blood sugar is 122 • Dawn phenomenon • To correct: Move evening NPH to bedtime
- 59. Case 2 • What if 2AM blood sugar was 59? • Somogyi phenomenon – rebound hyperglycemia after hypoglycemia • Treatment: decrease evening NPH
- 60. Mary Tyler Moore Type 1 diabetes
- 61. Case 3 • 13 y/o black female, 2 week h/o polyuria, polydipsia, 16 lb weight loss • Overweight, BMI 97% • Acanthosis nigricans on neck • 2 grandparents have type 2 diabetes
- 62. Case 3 • Initial glucose – 634 mg/dl • Bicarb – 18 mmol/l • UA >80 mg/dl ketones • Serum ketones – negative • Type 1 or type 2?
- 63. Risk Factors for Type 2 • Obesity • Acanthosis nigricans • Family history • Maternal gestational diabetes
- 64. Case 3 • Islet cell antibodies – positive • Anti-GAD 65 – positive • Insulin antibodies – negative • C-peptide - <0.5 • Type 1
- 65. Sick Day Management • Never omit insulin • Insulin requirements are often greater with illness • Hypoglycemia may be a problem, especially in younger children • Test blood sugars every 2-4 hours • Check urine ketones
- 66. Sick Day Management • Drink plenty of fluids (1 cup per hour) – Sugar-containing liquids for hypoglycemia • Need extra insulin to clear ketones – NPH/R: extra 20% of total dose as R q4 hours – Basal/bolus: correction dose q3 hours + additional 20% of calculated correction • ED for persistent vomiting
- 67. Halle Berry Actress Type 1 diabetes
- 68. New Directions: Inhaled Insulin
- 69. PREP Questions
- 70. Question Which of the following statements regarding the development of type 1 diabetes is true? A. Administration of parenteral insulin to those at risk has been proven to decrease the likelihood of developing diabetes B. HLA typing has not been shown to be useful in determining the risk of developing diabetes C. Most patients have complete destruction of the beta cells, with no residual function at the time of diagnosis. D. The presence of antibodies against islet cells and insulin can be predictive of the risk of developing diabetes.
- 71. Answer • D. The presence of antibodies against islet cells and insulin can be predictive of the risk of developing diabetes.
- 72. Question Which of the following statements regarding insulin therapy is true? A. Inhaled insulin is not effective in children. B. Insulin pump therapy should be reserved for noncompliant adolescent patients. C. Insulin therapy should be discontinued temporarily during the “honeymoon” period. D. Rapid-acting insulin is beneficial because it decreases glycosylated hemoglobin levels over time. E. Use of rapid-acting insulin can decrease postprandial hyperglycemia and night-time hypoglycemia.
- 73. Answer • E. Use of rapid-acting insulin can decrease postprandial hyperglycemia and night-time hypoglycemia.
- 74. Question • You are seeing a 9 y/o boy who was diagnosed with type 1 diabetes 2 years ago. He currently receives 2 daily injections of short- and intermediate- acting insulin. As part of your evaluation, you ask to see his blood glucose diary. You note that most of his readings over the last month have been around 200 mg/dL. His mother is unwilling to try a pump at this point.
- 75. Question Which of the following management options is best? A. Increase the evening dose of short-acting insulin. B. Increase the morning dose of intermediate-acting insulin. C. Increase the morning dose of short-acting insulin. D. Obtain a hemoglobin A1c level, and if it is normal, continue the current insulin regimen. E. Split the evening dose to administer intermediate- acting insulin at bedtime.
- 76. Answer • E. Split the evening dose to administer intermediate-acting insulin at bedtime.
- 77. SSG Mark Thompson Deployed to Iraq with Type 1 Diabetes
- 78. Resources • www.childrenwithdiabetes.com • Clinical Practice Recommendations: January Diabetes Care, ADA website • American Diabetes Association • Juvenile Diabetes Research Foundation