1. TYPE 2 DIABETES MELLITUS Cynthia Brown, MN, ANP, CDE

2. Type 2 Diabetes Mellitus  Epidemiology: 25 million Americans or 8.3% 7 million undiagnosed 1.9 million older than 20 diagnosed in 2010 7 th leading cause of death In 2007, cost of treating $174 billion 1.5 million >20 diagnosed per year

3. Type 2 Diabetes Mellitus  Epidemiology: Leading cause of ESRD, blindness, amputation, & impotence Heart disease & stroke 2-4 times more common 90-95% of persons with diabetes have Type 2

4. Type 2 Diabetes Mellitus  Populations at risk: Those older than 30 Some children now diagnosed African Americans Native Americans Hispanics Asians Pacific Islanders

5. Type 2 Diabetes Mellitus  Populations at risk: Family history in 1 st or 2 nd degree relative Hx gestational diabetes or baby >9 lbs Signs of insulin resistance Hx pre-diabetes Hx vascular disease Physical inactivity

6. Type 2 Diabetes Mellitus  Diagnosing: 1979: original WHO criteria-  FBS >140  2 hour >200 1997: ADA  Type 1  Type 2  Eliminated all other references to age, insulin usage

7. Type 2 Diabetes Mellitus  Diagnosing: 1998: ADA  Lowered FBS to 126  Based on association between glucose levels & development of retinopathy 2011: ADA accepted A1c >6.5% as diagnostic; <6.5% does not exclude diagnosis

8. Type 2 Diabetes Mellitus  Today’s testing methods: Fasting plasma glucose 1-2 hour post meal can be used; if >140, further testing indicated FPG <100mg/dl=normal FPG >100 & <126 = IFG & pre- diabetes FPG >126=diabetes

9. Type 2 Diabetes Mellitus  Oral glucose tolerance test still the gold standard 150 grams carb for 3 days prior 10-14 hour fast 75 gram glucose load No activity during test Do not perform in the ill, malnourished

10. Type 2 Diabetes Mellitus  Impaired Glucose Tolerance (IGT)  Impaired Fasting Glucose (IFG)  Glucose higher than normal, but not diagnostic of diabetes  IGT: random or 2-hour glucose >140 but <200  IFG: FPG >100 but <126

11. Type 2 Diabetes Mellitus  When to screen: Start at age 45; every 3 years if normal Start younger if overweight or risk factors present Anytime fasting blood sugar not normal Easiest is a fingerstick Must note time of last food

12. Type 2 Diabetes Mellitus  Metabolic Defects: Cellular resistance to effect of insulin Failing beta cells Loss of first phase response Decreased secretion of amylin Decreased secretion of incretins

13. Type 2 Diabetes Mellitus  Each metabolic defect causes a different problem Cellular resistance causes high circulating insulin levels Leads to fatigue and weight gain Low amylin-rapid emptying of stomach Low incretins-no sense of fullness Also problems with insulin secretion

14. Type 2 Diabetes Mellitus  Chronic disease syndrome associated with insulin resistance: Metabolic Syndrome Dysmetabolic Syndrome Syndrome X

15. Type 2 Diabetes Mellitus  Syndrome features: Central or visceral obesity Dyslipidemia Atherosclerosis Endothelial dysfunction Decreased fibrinolytic activity=pro- thrombotic Hypertension Acanthosis

16. Type 2 Diabetes Mellitus  Syndrome Features: PCOS Hyperuricemia Pre-diabetes

17. Type 2 Diabetes Mellitus  Inherited defect in insulin action Abnormal insulin signaling Abnormal glucose transport Abnormal glycogen synthesis Abnormal mitochondrial oxidation  Hyperinsulinemia by downregulation of insulin receptor numbers & post- receptor events

18. Type 2 Diabetes Mellitus  Enhanced lipolysis with elevation of free fatty acids aggravates insulin resistance  Impairs glucose uptake at muscle  Enhances hepatic glucose production  Islet cell impaired in release of insulin

19. Type 2 Diabetes Mellitus  Impaired glucose tolerance & overt diabetes develop when beta cells fail  Cause of “pancreatic exhaustion” unknown  When FBS 115, first phase insulin secretion lost

20. Type 2 Diabetes Mellitus  When FBS 180, all phases of insulin secretion markedly impaired.  Gastric emptying accelerated  Post prandial hyperglycemia  Defects in appetite control & satiety  All treatments aimed at these metabolic defects

21. Type 2 Diabetes Mellitus  Insulin resistance: Start with insulin sensitizers-  Metformin(biguanide)  Actos (TZD)  Both re-sensitize person to own insulin  Very different mechanisms  Work at liver, muscle, islet cell

22. Type 2 Diabetes Mellitus  Pancreatic stimulators: Glipizide, glyburide, glimepiride (sulfonylureas) Prandin, Starlix (secretagogues) Rapid acting beta cell stimulators Interact with ATP-dependent potassium channels of beta cells Glucose dependent action

23. Type 2 Diabetes Mellitus  Januvia, Onglyza, Tradjenta (DPP-4 inhibitors) Slows inactivation of incretin hormones Concentrations of GLP-1 & GIP increase Enhances insulin release in glucose- dependent manner Suppress hepatic glucose production Lowers post-meal glucose levels

24. Type 2 Diabetes Mellitus  Byetta, Victoza (incretin mimetics) Glucoregulatory effects similar to glucogon-like peptide-1 (GLP-1) Secreted by gut in response to food Very short half-life Restore first-phase insulin response Suppress post-meal glucagon Slows gastric emptying

25. Type 2 Diabetes Mellitus  Precose, Glyset (alpha glucosidase inhibitors) Act locally in intestine Slows digestion of carbohydrates Delays absorption of glucose GI side effects

26. Type 2 Diabetes Mellitus  Insulins: Basal: Lantus, Levemir, NPH Bolus: Humalog, Novolog, Apidra, Regular Given in patterns to mimic mother nature

27. Type 2 Diabetes Mellitus  Thank you very much for your attention!  Questions?