Diabetes Mellitus

1. Diabetes Mellitus Type 1 and Type 2 Gary Strokosch, MD Region III & V Medical Specialist April 18, 2019

2. Diabetes Mellitus • Type 1: formerly known as insulin-dependent diabetes mellitus (IDDM) or juvenile onset diabetes • Type 2: formerly known as non-insulin-dependent diabetes mellitus (NIDDM) or adult onset diabetes

3. Type 1 Diabetes • Type 1 accounts for only 10% of all cases of diabetes, but demands daily treatment with insulin. • Type 1 patients have a variety of symptoms during a brief latency period. • Type 1 students will have been diagnosed before JC

4. Diagnosis • A diagnosis of diabetes is made if the fasting glucose is >125 mg/dL, or if a 2-hour GTT results in a glucose >200 mg/dL • However, one abnormal glucose value is all that is needed in a patient with classical symptoms of diabetes, such as polyuria or polydipsia. • A HgA1C (A1C) ≥6.5% was added in 2010. • The diagnosis of diabetes should never be made on the basis of glucose in the urine (glycosuria).

5. Pre-DiabetesVs.Diabetes

6. Glucohemoglobin • HbA1C is a measure of integrated glucose control over the preceding 2-3 months and reflects the average life of a red blood cell. • Glucose becomes attached to hemoglobin in a non-enzymatic fashion that is dependent on the average concentration of blood glucose.

7. Glucohemoglobin

8. The DiabetesTreatmentGame Changer • 1921: Frederick G. Banting, Charles H. Best, J.J.R. Macleod and James B. Collip discovered insulin. • The first patients with diabetes were treated with insulin.

9. Insulin Discovery Books • “The Discovery of Insulin” by Michael Bliss • “Breakthrough: Elizabeth Hughes, the Discovery of Insulin, and the Making of Medical Miracle” by Arthur Ainsberg and Thea Cooper • “The Fight to Survive: A Young Girl’s Struggle with Diabetes and the Discovery of Insulin” by Caroline Cox

10. Insulin Treatment History • 1921/22: Insulin was initially from bovine and later porcine sources. • 1980: Recombinant human insulin manufactured from E. Coli is introduced. • 1995: The first basal (long acting) insulin was introduced. • 1996: Analogue (rapid acting) insulins were introduced

11. Etiology of T1 • Type 1 diabetes is cause by an absolute deficiency of insulin, a hormone which is produced in the beta cells of the Islets of Langerhans in the pancreas. • Although poorly understood, it is likely that (1) some environmental factor triggers a (2) selective autoimmune destruction of the beta cells (3) in a genetically predisposed individual.

12. T1 Presenting Symptoms • Polyuria / Nocturia • Thirst • Polydipsia • Polyphagia • Weight Loss • Ketoacidosis Progression

13. Diabetic Ketoacidosis:A Rapid Onset a Life-threatening Complication in T1 • Consists of hyperglycemia, ketosis and acidosis • 10-25% of episodes of DKA result from new patients presenting for the first time • 30-40% of episodes are from infections • Most of the rest of the episodes are from stopping insulin! • NB: 1-2% mortality during each episode

14. Mortality / Morbidity • Prior to 1921 the development of type 1 diabetes meant an almost certain death shortly after diagnosis. • A significant proportion of deaths in young diabetics are attributable to DKA. • Later deaths are more commonly associated with cardiovascular and renal disease in older patients.

15. Chronic Complications • Retinopathy: most common cause of blindness in people of working age • Nephropathy: 20-44% of all new patients needing renal replacement therapy have diabetes • Erectile Dysfunction: may affect up to 50% of men with long-standing diabetes • Macrovascular Disease: 2-3 fold increased risk of coronary heart disease and stroke • Foot Problems: 15% of people with diabetes develop foot ulcers; 5-15% of people with diabetic foot ulcers need amputations

16. Applicant File ReviewInterview with Applicant • Treatment of type 1 diabetes is NOT optional. Does the applicant agree with the diagnosis and need for daily injections? Does the student think this disease will eventually go away? Who has s/he been seeing for diabetes care and how often? How do they reach that individual when there is a problem? How many ER visits or hospitalizations in the past year?

17. AFR • How long has applicant been in treatment? Some new patients have a “grace period” of weeks or months with minimal need for insulin after starting treatment. Management plans change frequently during the first few months of treatment and can require repeated adjustments of insulin timing and dose.

18. AFR • What are the specifics of the treatment plan? e.g., the type(s) of insulin, is it the pens or vials, the prescribed schedule for administration, the sliding scale for meals, the schedule for BS measurements, is there an evening snack plan, etc. – plan for the details to be requested. You cannot know too much!

19. AFR • Highly effective self-management by an adolescent patient is unlikely and is not the criterion for entry into JC. Sometimes A1C levels can go very high (10-15%) – what does the applicant think is the reason it is high? • Episodes of DKA are usually related to stopping insulin for whatever reason. Why was it stopped?

20. AFR • Who performs the applicant’s injections and tests their blood sugar? Confirm this with a parent/guardian. • Are the insulin(s) and the supplies covered under insurance? What insurance? Who is the insured party? • Have you ever been on an insulin pump? Was it discontinued? If so, why? How are the supplies ordered and who pays for them?

21. Treatment of T1 • Basal and bolus insulin • Estimation of carbohydrate intake • Moderate exercise

22. Insulin Names Generic Brand Novolog Humalog Apidra Humulin R / Novolin R Humulin N / Novolin N Levemir Lantus • aspart • lispro • glulisine • regular • NPH • determir • glargine

23. Insulin Action NPH = Neutral Protamine Hagedorn

24. Bolus Action • Rapid Acting • Novolog • Humalog • Apidrah • Short Acting • Humulin R • Novolin R • Onset: 10-15 min • Peak: 1-2 hrs • Duration: 3-4 hrs • Onset: 30-60 min • Peak: 2-3 hrs • Duration: 8-10 hrs

25. Basal Action • Intermed. Acting • NPH • Long Acting • Levemir • Lantus • Onset: 1-1½ hrs • Peak: 6-8 hrs • Duration: 8-16 hrs • Onset: 2-4 hrs • Peak: none • Duration: 14-24 hrs

26. Pre-mixed Insulins(biphasic) • Novolog mix: aspart+ NPH • 70/30 mix (vials and pens) • Humalog mix: lispro + NPH • 50/50 mix (vials and pens) • 75/25 mix (vials and pens) • Novolin mix: NPH / regular • 70/30 mix (vials) • Humulin mix: NPH / regular • 70/30 mix (vials and pens) • 50/50 mix (vials)

27. Treatment Regimens • Pre-mixed insulin twice daily • 2 injections daily • Basal-bolus regimen with rapid acting insulin at the three meals and long acting insulin at bed time • 4 injections daily • Continuous subcutaneous insulin infusion (CSII) or insulin pumps • 1 needle insertion every 3 days

28. Injection Sites FRONT BACK

29. Injection Site Side Effects • LIPOHYPERTROPHY: when insulin is repeatedly injected into the same site there can be a local tropic effect and lead to lumps at the site and compromise absorption of insulin • LIPOATROPHY: immunoglobulin G immune complexes against insulin can form and produce atrophy as well as compromise the action of insulin

30. Omnipod Insulin Pump

31. Medtronics Insulin Pump

32. Medtronics Connections

33. Hypoglycemia • When blood glucose falls below 63 mg/dL • The most common side effect of insulin therapy • A barrier to obtaining optimal glycemic control • Most type 1 patients will experience several mild episodes per week and 1-2 severe episodes per year needing outside help • Occurs more frequently in young patients and those under tight glycemic control

34. HypoglycemiaSigns / Symptoms • Autonomic • Sweating • Pins & needles • Feeling hot • Shakiness • Anxiety • Palpitations • Pallor • Neuroglycopenic • Difficulty speaking • Loss of concentration • Drowsiness • Dizziness • Hemiplegia • Fits • Coma • Non-specific • Nausea • Hunger • Weakness

35. DIABETES MELLITUS TYPE 2

36. Type 2 Diabetes Mellitus • It is the commonest type of diabetes • Accounts for 90% of diabetes cases • There are many undiagnosed cases in JC • The prevalence is increasing rapidly for unclear reasons – perhaps because of obesity • The WHO predicts cases doubling between the years 2000 and 2030 • Although the incidence increases with age, it is now also seen in young people • The lifetime risk of developing T2 is 1 in 10

37. Type 2 Diabetes Mellitus • Insulin resistance is cardinal but not limited to diabetes – NB: only about 20% of people with insulin resistance develop T2 • Insulin deficiency from pancreatic beta-cell dysfunction precedes the diagnosis of T2 by a decade and is only 50% normal at diagnosis • Beta-cell function deteriorates further at about ~4% per year!!

38. T2 Genetic Predisposition • Heritability accounts for 40-80% of total disease susceptibility • Maternal H/O diabetes confers a higher risk than a paternal history, which may be explained by an added intrauterine effect • Sum: No single gene explains T2 inheritance – it is polygenic

39. Environmental Predisposition • Estimated that 80% of new cases of T2 can be attributed to obesity • Fat distribution is also important • Increased visceral fat increases T2 risk (which is reflected in an increased waist circumference) • A sedentary life style can lead to obesity, but is also an independent risk factor for T2

40. Prevention of T2- HEALs - • Reducing weight • Reducing intake of fat, especially saturated fat • Increasing dietary fiber • Daily physical activity

41. Presentation • About 50% of T2 cases are diagnosed by symptoms of polyuria, nocturia, thirst, tiredness and/or blurry vision. • About 16% of T2 cases are diagnosed after presenting during an infection.

42. Diagnostic Criteria • FBS = ≥126 mg/dL • 2-hour oral glucose tolerance test with 75 gm glucose after an overnight fast = ≥200 mg/dL • A1C = ≥6.5% X2 (controversial) • Normal = 4.0 – 5.6% • Suspicious = 5.7 – 6.4% • Random BS ≥200 mg/dL with other symptoms of diabetes

43. Natural History Model for T2

44. Screening for T2 • Universal screening is impractical • Screening high-risk students is justified (undiagnosed T2 common) • Although the OGTT is the gold standard, it is inconvenient • A FBS is suitable, but is not as sensitive and may miss some • A1C screening in JC • Random BS of ≥200 mg/dL in JC

45. Common Pharmacologic Medications • Alpha-glucosidase Inhibtors (i.e., Acarbose) • Biguanides (i.e., Metformin) • Meglitinides (i.e., Repaglinide / Nateglinide) • Sulfonylureas (i.e., Tolazimide Glimepiride) • Thiazolidinediones (i.e., Rosiglitazone) • Injectibles (i.e., Exenatide / Sitagliptin)

46. Algorithm for T2 Treatment

47. PRH 6.12, R11: MSWR • Students are medically separated: • when they are determined to have a health condition that significantly interferes with or precludes further training in JC, • when the health problem is too complicated to manage, or • when the necessary treatment will be unusually costly.

48. Thank you for your attention. Questions?

49. AMERICAN DIABETES ASSOCIATION • Medical Management of Type 1 Diabetes, 7th Edition • Cecilia C. Low Wang, MD, FACP, and Avni C. Shah, MD, editors • ePUB: $31.49  Book: $44.95 • Updated 2017 edition presents the latest guidelines for the comprehensive management of type 1 diabetes and strategies to improve outcomes.

50. AMERICAN DIABETES ASSOCIATION • Medical Management of Type 2 Diabetes, 7th Edition • Charles F. Burant, MD, PhD, and Laura A. Young, MD, PhD, Eds. • ePUB: $31.49 Book: $44.95 • Diabetes mellitus type 2 health care professional guide. Comprehensive protocols for diagnosing and treating type 2 diabetes patients.