1. DIABETES Shantana Jones Clinical Seminar II

2. Prevalence  25.8 million children and adults have diabetes  Diagnosed: 18.8 million people  Undiagnosed: 7.0 million people  Pre-diabetes: 79 million people  1.9 million new cases of diabetes are diagnosed every year in people aged 20 years and older  About 1 in every 400 children and adolescents has diabetes

3. Ethnic Difference in Prevalence  7.1% of non-Hispanic whites  8.4% of Asian Americans  12.6% of non-Hispanic blacks  11.8% of Hispanics

4. Epidemiology  Type 1 diabetes accounts for 5% to 10% of all cases of diabetes  Type 2 diabetes accounts for as much as 90% of all cases of diabetes, and is largely the result of excess body weight and physical inactivity  WHO projects that diabetes will be the 7th leading cause of death in 2030

5. Pathophysiology

6. Type 1 Diabetes  Type 1 diabetes is also known as juvenile diabetes or childhood diabetes  Cellular-mediated autoimmune destruction of the beta cells in the pancreas  Absolute insulin deficiency  Onset: Early in life  Therapy must include insulin replacement

7. Type 2 Diabetes  Characterized by a combination:  Relative insulin deficiency  Insulin resistance  Associated with family history of diabetes, obesity, and physical inactivity  Onset: Later in life  Treatment includes: lifestyle modifications, oral medications, and/or insulin replacement

8. Risk Factors for Type 2 Diabetes  Family history  Ethnicity  Overweight (BMI > 25 kg/m 2 )  Pre-diabetes  History of gestational diabetes  Delivery of a baby weighing > 9 Ibs  Poor diet and low physical activity  Polycystic ovary syndrome (PCOS)  Hypertension  History of cardiovascular disease

9. Signs & Symptoms  Polyuria  Polyphagia  Polydipsia  Blurred vision  Fatigue  Weight changes  Loss (Type 1)  Gain (Type 2)  Slow healing of sores  Frequent infections  Diabetic Ketoacidosis (Type 1)  Numbness and tingling of the hands and feet

10. Diagnosis

11. Non-pharmacological Treatment

12. Lifestyle Modifications  Physical exercise:  150 min/week of moderate activity  Healthy diet:  Reduce calories and intake of fat  Increase fiber and whole grains  Limit protein intake to 0.8-1.0g/kg/day  Limit intake of sugar-sweetened beverages  Limit alcohol intake  Obese patients:  Weight loss 7% of body weight

13. Pharmacological Treatment

14. Insulin  Insulin is a protein that muscle and adipose tissue require for glucose uptake  Regulates fat storage and inhibits the breakdown of fat for energy

15. Insulin Replacement Insulin Type Onset (HR)DurationSide Effects Rapid acting: Insulin aspart Insulin glulisine Insulin lispro 0.25-0.503-5 Hypoglycemia Hypokalemia Injection site reaction Short acting: Regular 0.5-14-6 Hypoglycemia Weight gain Diabetic Ketoacidosis Intermediate acting: NPH 2-48-12 Hypoglycemia Diabetic Ketoacidosis Long acting: Insulin detemir Insulin glargine 2 4-5 14-24 24 Hypoglycemia Headache Injection site reaction

16. Biguanide  Decreases hepatic glucose production  Decreases intestinal absorption of glucose  Improves insulin sensitivity  Clinical Pearls:  Weight neutral  Beneficial for patients with CVD  Lowers A1C 1-2%  Pregnancy Category B

17. Biguanide DrugDosingContraindication/Side effects Metformin (Glucophage, Glucophage XR, Fortamet, Glumetza) IR: 500 mg daily-BID or 850 mg daily ER: 500-1000 mg with evening meal *max2,550 mg BBW: Lactic acidosis Contraindicated: SCr > 1.5 mg/dL(males) or >1.4(females) or CrCl <60mL/min GI effects Vit B12 deficiency

18. Sulfonylureas  Stimulates insulin secretion from beta cells  Do not use with meglitinides due to similar MOA  Clinical Pearls:  Lowers A1C 1-2%  Avoid use in elderly population  Weight gain  Pregnancy Category C

19. Sulfonylureas DrugDosingContraindications/Side Effects Chlorpropamide (Diabinase) 250 mg daily Hypoglycemia (long lasting) Weight gain Glipzide (Glucotrol, Glucotrol XL) IR: 5-10 mg BID XL: 2.5-10 mg daily *max 20 mg daily Hypoglycemia Weight gain Glimepiride (Amaryl)1-4 mg *max 8 mg daily Hypoglycemia Weight gain Glyburide (Diabeta)1.25-5 mg daily *max 20 mg/d Contraindicated: CrCl <50 mL/min Hypoglycemia Weight gain

20. Meglitinides  Stimulates insulin secretion from the beta cells  Do not use with sulfonylureas due to similar MOA  Clinical Pearls:  Lowers A1C 0.5-1.5%  Used to decrease postprandial BG  Weight gain  Pregnancy Category C

21. Meglitinides DrugDosingContraindications/Side Effects Repaglinide (Prandin)A1C <8%: 0.5 mg TID A1C >8%: 1-2 mg TID Hypoglycemia Weight gain Upper respiratory tract infection Nateglinide (Starlix)60 mg TID if near A1C or 120 mg TID Hypoglycemia Weight gain Upper respiratory tract infection

22. Thiazolidinediones (TZD)  TZDs are peroxisome proliferator-activated receptor gamma (PPAR γ ) agonists  Increases peripheral insulin sensitivity Increases the uptake and utilization of glucose by peripheral tissues  Clinical Pearls:  Lowers A1C 0.5-1.4%  Use with caution in patients with CHF  May cause bone loss

23. Thiazolidinediones (TZD) DrugDosingContraindications/Side Effects Pioglitazone (Actos)15-30 mg daily *max 45 mg daily BBW: may cause or exacerbate heart failure in some patients Edema Weight gain Increase fracture risk Increase risk of bladder cancer >1 year Rosiglitazone (Avandia)4-8 mg daily BBW: may cause or exacerbate heart failure in some patients Edema Weight gain Increase fracture risk REMS program

24. Alpha-Glucosidase Inhibitors  Inhibit alpha-glucosidase in the intestines  Delayed absorption of glucose  Inhibit metabolism of sucrose to glucose and fructose  Clinical Pearls:  Lowers A1C 0.5-0.8%  Used to decrease postprandial BG  Improves cholesterol levels  Pregnancy Category B

25. Alpha-Glucosidase Inhibitors DrugDosingContraindications/Side Effects Acarbose (Precose)25 mg with each with *max 300 mg/d divided Contraindicated: Inflammatory bowel disease, colonic ulceration, partial or complete intestinal obstruction GI effects Miglitol (Glyset)25 mg with each with *max 300 mg/d divided Contraindicated: Inflammatory bowel disease, colonic ulceration, partial or complete intestinal obstruction GI effects

26. DPP4-Inhibitors  Prevent the enzyme DPP-4 from breaking down incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP)  Hormones help regulate blood glucose levels  Increases insulin release from beta cells  Decreases glucagon secretion from alpha cells  Incretin enhancers  Clinical Pearls:  Lowers A1C 0.5-0.8%  Decrease postprandial BG

27. DPP4-Inhibitors DrugDosingContraindications/Side Effects Sitagliptin (Januvia)100 mg daily 25 mg with Hypoglycemia Nasopharyngitis Upper respiratory tract infection Angioedema Acute pancreatitis Saxaglliptin (Onglyza)5 mg daily 2.5 mg if CrCl <50ml/min or with strong CYP 3A4 inhibitors Peripheral edema Hypoglycemia Nasopharyngitis Upper respiratory tract infection Linagliptin (Tradjenta)5 mg daily Hypoglycemia Napsopharyngitis Pancreatitis

28. Glucagon-Like Peptide-1 (GLP-1) Agonist  Analogs of glucagon-like peptide-1 (GLP-1)  Increases insulin secretion  Decreases glucagon secretion  Slow gastric emptying  Improves satiety  Incretin mimetics  Clinical Pearls:  Lowers A1C 0.5-1%  Decrease postprandial BG

29. Glucagon-Like Peptide-1 (GLP-1) Agonist DrugDosingContraindications/Side Effects Exenatide (Byetta) Exenatide (Bydureon) IR: Initial 5 mcg SC BID for 1 month; then 10 mcg SC BID ER: Inject 2 mg SC every 7 days Contraindicated: severe impairment CrCl <30 ml/min Injection site reaction Hypoglycemia Nausea/Vomiting Weight loss Pancreatitis Liraglutide (Victoza)Initial 0.6 mg SC daily x 1 week, then 1.2 mg SC daily x 1 week Pancreatitis Acute renal failure Hypoglycemia

30. Type 1 & 2 Diabetes  Pramlintide (Symlin): synthetic analog of the human neuroendocrine hormone, amylin  Amylin is produced by the pancreatic beta cells to assist in postprandial glucose control  Amylin helps slow gastric emptying, prevent an increase in serum glucagon following a meal, and increase satiety

31. Type 1 & 2 Diabetes DrugDosingContraindications/Side Effects Pramlintide (Symlin)Type 1: Initial 15 mcg immediately to meals Type 2: Initial 60 mcg prior to meals Contraindication: gastroparesis, hypoglycemia unawareness Hypoglycemia Nausea Anorexia Weight loss

32. Counseling Tips:  Insulin vials or pens in current use are good for 30 days at room temperature  Injection sites: abdomen, upper arm, buttocks, and thigh  If using Glumetza, Fortamet, or Glucophage XR, you may see a shell of the medicine in the stool  Avoid alcohol use  Symptoms of pancreatitis, which include severe stomach pain that does not go away, with or without vomiting

33. Counseling Tips:  Symptoms of hypoglycemia: shakiness, irritability, hunger, confusion, drowsiness, weakness, dizziness, sweating, and fast heartbeat. Always keep a source of sugar available in case you have symptoms of low blood sugar  Glipizide IR is taken 30 minutes prior to breakfast  TZDs may take several weeks for the drug to lower blood sugar; monitor your levels carefully  Alpha-Glucosidase Inhibitors take with a full glass of water, with the first bite of food

34. Special population  Gestational Diabetes: onset during pregnancy  Pre-prandial blood glucose should be < 95 mg/dL  Postprandial < 140 mg/dL 1 hours post meal or < 120 mg/dL 2 hours post meal  A1C < 6%  Insulin therapy: Regular NPH

35. Summary:  Diabetes is a disease in which the body does not produce or properly use insulin  Increased risk for heart disease and stroke  ABC’s of Diabetes:  A1C ✔ quarterly or twice a year Reduce to < 7%  Blood pressure Lower BP < 130/80  Cholesterol Aim for LDL < 100 mg/ dL

36. References:  "CDC - 2011 National Diabetes Fact Sheet - Publications - Diabetes DDT." Centers for Disease Control and Prevention. N.p., n.d. Web. 29 Sept. 2013..  "Diabetes Basics - American Diabetes Association®." American Diabetes Association Home Page - American Diabetes Association®. N.p., n.d. Web. 28 Sept. 2013..  Shapiro, Karen, and Sherry A. Brown. "Diabetes." RxPrep course book. 2013 ed. San Diego, Calif.: RxPrep, 2013. 344-371. Print.