Diabetes Change Agent A National Pilot Program

1. Diabetes Change AgentA National Pilot Program

2. PreTest • Name the three ways diabetes can be diagnosed? • What is the LDL goal for diabetics? • What is the optional LDL goal? • What is the A1C goal? • What is the BP goal? • What is the BP goal in patients with nephropathy?

3. Pre-Diabetes Definition If FBG >100 there is a 10-15% risk of DM within 7 years… or Fasting GTT

4. Metabolic Syndrome Elevated insulin level, fasting glucose or postprandial glucose and any 2 of the following: Triglyceride ≥ 150 or HDL ≤ 35 Blood pressure ≥ 140/90 or on medication for HTN Waist to hip ration > 0.9, a BMI ≥ 30 or waist circumference > 37 inches WHO Guidelines Any three of the following: Waist circumference >40 inches – men >35 inches – women Triglycerides ≥150 HDL ≤ 40 (men) or ≤ 50 (women) Fasting glucose ≥ 100 -- Hypertension ATP III Guidelines

5. Treatment of Metabolic Syndrome TLC: Therapeutic Lifestyle Changes Smoking cessation Increasing physical activity Weight reduction Healthy meal planning Pharmacotherapy Management of blood pressure Management of lipids Management of blood glucose Aspirin for CVD prevention

6. Pharmacotherapy – Metabolic Syndrome Always use TLC first and continue along with pharmacotherapy! Treat Lipids If patient has ↑ TG and ↓ HDL, treat TG If patient has ↑ LDL & TG and ↓ HDL, treat LDL first then treat TG Treat LDL with statins Treat TG & HDL with fibrates and niacin

7. Pharmacotherapy – Metabolic Syndrome Treat hypertension to goal (< 130/80) Low dose diuretic initially 66% will require 2 meds to control ACE inhibitor, ARBs, Calcium channel blockers Only 54% are treated for HTN Of those treated, only 28% are at goal

8. Pharmacotherapy – Metabolic Syndrome Treat clotting disorder Daily low dose aspirin (81-325 mg) for men over age 45 and postmenopausal women Treat blood glucose Insulin sensitizers Metformin and TZDs [pioglitazone (Actos) and rosiglitazone (Avandia)]

9. According to the American Diabetes Association 20.8 million children and adults in the U.S. have diabetes 14.6 million have been diagnosed with diabetes 6.2 million are unaware that they have the disease Diabetes represents 11% of the U.S. healthcare expenditure 1 out of every 10 health care dollars spent in the U.S. is spent on diabetes and its complications

10. Diabetes Classifications Pre-Diabetes Blood glucose levels are higher than normal but not high enough to be diagnosed with diabetes Risk factor for future diabetes and cardiovascular disease Type 1 Diabetes Type 2 Diabetes Gestational Diabetes Pregnant women who have never had diabetes but who have high blood glucose levels during pregnancy

11. Screening Individuals ≥45 years of age, particularly if BMI ≥25 kg/m2 Individuals <45 years of age and overweight with other risk factors for diabetes Are habitually physically inactive Have a first-degree relative with diabetes Are members of a high-risk ethnic population (African American, Latino, Native American, Asian American , Pacific Islander) Have delivered a baby weighing >9 lbs or have been diagnosed with gestational DM Are hypertensive (≥140/90 mmHg) Have an HDL cholesterol level <35 mg/dl and/or a triglyceride level >250mg/dl Have polycystic ovary syndrome On previous testing had impaired glucose tolerance or impaired fasting glucose Have other clinical conditions associated with insulin resistance Have a history of vascular disease

12. Diagnosis Three ways to diagnosis Fasting plasma glucose (FPG) Oral glucose tolerance test (OGTT) Symptoms of diabetes and a casual plasma glucose ≥200 mg/dl Each diagnostic criteria must be confirmed on a subsequent day unless unequivocal symptoms of hyperglycemia are present.

13. Complications Heart Disease and Stroke Heart disease death rates are 2 to 4 times higher than adults without DM The risk for stroke is 2 to 4 times higher than adults without DM High Blood Pressure 73% of adults with DM have a blood pressure greater than or equal to 130/80 mmHg or use prescription medications for hypertension Blindness Diabetic retinopathy is the leading cause of new cases of blindness in adults Kidney Disease Diabetes is the leading cause of kidney failure Nervous System Disease 60% to 70% of patients have mild to severe forms of nervous system damage. 30% of patients age 40 years or older have impaired sensation in the feet.

14. Complications Amputations More than 60% of non-traumatic lower-limb amputations are due to DM. The rate of amputation is 10 times higher in patients with DM. Dental Disease Periodontal (gum) disease is more common in DM patients. Complications of Pregnancy Poorly controlled DM before conception and during 1st trimester can cause major birth defects in 5% to 10% of pregnancies and 15% to 20% of spontaneous abortions. Poorly controlled DM during the 2nd and 3rd trimester can result in large babies. Sexual Dysfunction Men with DM are 2 times are likely to experience erectile dysfunction. Life-threatening Events Diabetic ketoacidosis (DKA) Infection DM patients are more susceptible to infection and have worse prognoses.

15. Complications and Preventative Care • Self-Management Training (education) • Blood Pressure Control • Lipid Management • Anti-Platelet Agents • Retinopathy • Nephropathy • Foot care • Smoking Cessation • Immunizations

16. Annual foot exam Condition of the skin, hair and toenails Musculoskeletal Deformities Pedal Pulses Sensory Exam Footwear assessment

17. Sensory Exam Test five sites per foot. The total duration of the approach, skin contact, and departure of the filament at each site should be approximately 1 to 2 seconds.

18. Footwear Assessment • Examine the inside of the shoes • Look at the type of footwear • Look at the fit of the footwear • Is the footwear appropriate? • Would the patient benefit from corrective footwear? • From inserts?

19. Diabetic Retinopathy 20 million diabetics in US 50% undiagnosed Only 50% of known diabetics receive appropriate eye care Therefore, DR is leading cause of blindness in working-age population in US Prevalence of DR increases with duration of diabetes (100% Type 1, 60% Type 2 after 20 years)

20. Pathophysiologyof DR Increased blood sugar shunts excess into aldose reductase pathway leading to sorbitol > loss of capillary intramural pericyte function causing weakness and outpouching of capillary walls Microaneurysms> increased leakage> rupture> hypoxia> infarction of nerve fiber layer (cotton-wool spots)> Compensation for hypoxia leads to vasoproliferation, neovascular changes> extension into vitreous > vitreal hemmorrhage, fibrosis with traction

21. Classification of DR Mild non-proliferative (aka Background)- microaneurysms Moderate non-proliferative-small vessel occlusion Severe non-proliferative-increased vessel occlusion Proliferative-abnormal vessel development and extension

22. Diabetic Drug Classes Insulin Sulfonylureas Meglitinides Biguanides Alpha-glucosidase Inhibitors Thiazolidinediones Dipeptidyl Peptidase IV Inhibitor Combinations Amylinomimetic Incretin Mimetic

23. Indications for Insulin • Not contraindicated at anytime • Consider as initial therapy • HgbA1C > 10% • Fasting glucose > 250mg/dl • Random glucose > 300 • Recommended as initial therapy • Polyuria, polydipsia, weight loss, ketones

25. Rapid (Glulisine,Lispro, Aspart,) Long (Glargine) Insulin ActionEffect Of Various Formulations 140 120 100 Short (Regular) Insulin Level (U/ml) 80 Intermediate (NPH) 60 40 Detimir 20 0 0 2 4 6 8 10 12 14 16 Hours

26. Once Daily Insulin OptionsBasals vs. NPH vs. Premixed

27. Common Concerns When Transitioning To Insulin • Adverse impact on lifestyle; inconvenient; loss of personal freedom and independence • Belief that insulin means diabetes is worse or more serious disease • Insulin as a personal failure • Insulin causes complications • Treated differently by family members Funnel M. Self-management support for insulin therapy in type 2 diabetes. The Diabetes Educator 2004;30:274

28. Insulin InitiationAnswers to Provider Concerns • Normalize the fasting glucose • Fasting FSBS 70-130 • Once Daily Options • Start 10 units or 0.2 u/kg • Basal Insulin (glargine or detemir) • NPH (bedtime) • Premixed before dinner • Increase 2-3 units every 3 days prn to reach target of 70-130 fasting • Decrease 3 units for fasting < 70

29. Sulfonylureas First Generation Acetohexamide (Dymelor®) Chlorpropamide (Diabinese®) Tolazamide (Tolinase®) Tollbutamide (Orinase®) Second Generation Glipizide (Glucotrol®, Glucotrol XL®) Glyburide (Diabeta®, Micronase®) Micronized Glyburide (Glynase®) Glimepiride (Amaryl®) Place in Therapy: Reasonable first line in type 2 DM Mechanism of Action: Stimulate pancreas to make more insulin Adverse Effects: Hypoglycemia, upset stomach, skin rash or itching, weight gain

30. Meglitinides Repaglinide (Prandin®) Netaglinide (Starlix®) Mechanism of Action: Stimulate the pancreas to make more insulin Administration: Take 30 minutes before meals, skip dose if meal is skipped Adverse Effects: hypoglycemia, weight gain

31. Biguanides Metformin (Glucophage®, Glucophage XR®, Fortamet®) Mechanism of Action: decrease the amount of glucose made by the liver Administration: with a meal Advantage: weight loss and improvement in cholesterol Adverse Effects: nausea, diarrhea, abdominal pain metallic taste in mouth Slow titration and take with food help resolve effects

32. Biguanides Lactic Acidosis: serious adverse effect Symptoms: weakness, malaise, heavy labored breathing High risk: renal dysfunction, liver dysfunction, cardiorespiratory dysfunction, or alcohol intake Contraindications: renal impairment (GFR <60 ml/min, SCr >1.4 for females or 1.5 for males) hepatic disease congestive heart failure requiring pharmacologic treatment history of lactic acidosis Precaution: Hold 48 hours before and after iodinated parenteral contrast dye procedure

33. Alpha-Glucosidase Inhibitors Miglitol (Glyset®) Acarbose (Precose®) Mechanism of Action: Slow the absorption of the starches consumed Administration: 3 times a day with the first bite of a meal Adverse Effects: gas, bloating, diarrhea, abdominal pain Minimize with slow titration; effects lessen over time If hypoglycemia occurs, administer oral glucose Sucrose will not be absorbed by these medications

34. Thiazolidinediones Pioglitazone (Actos®) Rosiglitazone (Avandia®) Mechanism of Action: Help cells become more sensitive to insulin Adverse Effects: hepatotoxicity, cardiovascular, edema, weight gain Monitor liver enzymes Avoid in patients with advanced heart disease or congestive heart failure Drug Interaction: Potential reduction of oral contraceptive efficacy Disadvantage: takes up to 12 weeks to work

35. Dipeptidyl Peptidase IV Inhibitor Sitagliptin (Januvia®) Indication: Patients with type 2 diabetes Mechanism of Action: DDP 4 Inhibitor enhance the body’s own ability to keep blood glucose levels balanced. Increases insulin levels and reduce the amount of sugar made in the liver when food is consumed

36. Dipeptidyl Peptidase IV Inhibitor Dosing: one 100mg once daily with or without food Adverse Effects: upper respiratory infections, stuffy or runny nose, sore throat, and headache Similar to placebo The use of JANUVIA in combination with medications known to cause hypoglycemia, such as sulfonylureas or insulin, has not been adequately studied. Research is ongoing. Coming soon: Vildagliptin (Galvus®)

37. Combinations Glimepiride and Rosiglitazone (Avandaryl®) Glimepiride and Pioglitazone (Duetact®) Glyburide and Metformin (Glucovance® ) Glipizide and Metformin (Metaglip®) Rosiglitazone and Metformin (Avandamet®) Pioglitazone and Metformin (ACTOplus Met®) Sitagliptin and Metformin (Janumet®)

38. Amylinomimetic Pramlintide acetate (Symlin®) Mechanism of Action: Synthetic analog of amylin Amylin is a hormone co-secreted with insulin Prolongs gastric emptying time in the stomach Reduces postprandial (after meals) secretion of glucagon (sugar made by liver) Reduces calorie intake through centrally-mediated appetite suppression Indications: Type 1 or 2 diabetes Adjunct treatment in patients using mealtime insulin who have failed optimal insulin therapy

39. Amylinomimetic Dosing: Prescription written in mcg and patients use units to draw the medication up in a syringe If Dose Is: Draw Up This Amount In Syringe: 15 micrograms 2.5 units 30 micrograms 5 units 45 micrograms 7.5 units 60 micrograms 10 units 120 micrograms 20 units Administration: inject in abdomen or thigh before a meal do not mix in the same syringe with insulin reduce the amount insulin by 50% when starting therapy Storage: Unopened vials in refrigerator and opened vials in refrigerator or room temperature for up to 28 days

40. Amylinomimetic Adverse Effects: nausea, hypoglycemia Contraindications: Known hypersensitivity to symlin or components Confirmed diagnose of gastroparesis Recurrent severe hypoglycemia in past 6 months Hypoglycemia unawareness A1C >9% Pediatric patients

41. Incretin Mimetic Exenatide (Byetta®) Derived from the gila monster salvia Mechanism of Action: Analog of hormone incretin (glucagon-like peptide 1 or GLP 1) Increases insulin secretion Prolongs gastric emptying time in the stomach Decrease appetite Suppresses glucagon Indications: Adjunctive therapy in type 2 diabetes who have not achieved desired glycemic control while taking metformin, a sulfonylurea, or both.

42. Incretin Mimetic Dosing: Administer up to 60 minutes before morning and evening meals Do not have to adjust based on size of meal or amount of exercise Administration: Inject subcutaneously in thigh, abdomen, or upper arm Use a new needle with each injection

43. Incretin Mimetic Storage: Store pens in the refrigerator and discard in 30 days Adverse Effects: nausea, hypoglycemia Drug Interactions: Slow down how quickly medications enter the bloodstream Consider taking medications like antibiotics and contraceptive pills 60 minutes before Byetta

45. Type 2 Diabetes Risk Factors • Family history of diabetes is very important • The dramatic increase in Type 2 Diabetes can be attributed to obesity and lack of physical activity • 80% of persons with Type 2 Diabetes are overweight or obese

46. Obesity: A Risk Factor • The U.S. Preventive Services Task Force (USPSTF) recommends that clinicians screen all adult patients for obesity by BMI and offer intensive counseling and behavioral interventions to promote sustained weight loss for obese adults. • Waist circumference, measured by the clinician, helps to assess further risk of obesity. http://www.ahrq.gov/clinic/uspstf/uspsobes.htm

47. 340 200 130 160 210 140 150 170 190 220 230 250 260 270 280 290 320 360 120 180 240 300 380 400 23 22 21 19 18 17 16 15 15 25 24 22 21 20 19 18 17 16 27 26 24 23 21 20 19 18 17 29 27 26 24 23 22 20 19 18 31 29 28 26 24 23 22 21 20 33 31 29 27 26 24 23 22 21 35 33 31 29 27 26 24 23 22 37 35 33 31 29 27 26 24 23 39 37 34 32 30 29 27 26 24 41 38 36 34 32 30 29 27 26 43 40 38 36 34 32 30 28 27 45 42 40 37 35 33 31 30 28 47 44 41 39 37 35 33 31 29 49 46 43 40 38 36 34 32 30 51 48 45 42 40 37 35 33 32 53 49 46 44 41 39 37 35 33 55 51 48 45 43 40 38 36 34 57 53 50 47 44 42 39 37 35 59 55 52 49 46 43 41 39 37 63 59 55 52 48 46 43 41 40 66 62 58 55 52 49 46 44 41 70 66 62 58 55 52 49 46 44 74 70 65 61 58 55 52 49 46 78 73 69 65 61 57 54 51 49 60 62 64 66 Height (in) 68 70 72 74 76 Body Mass Index Chart Weight (lb) http://www.obesityonline.org

48. BMI-Associated Disease Risk • Additional risks: • Large waist circumference (men>40 in; women >35 in) • 5 kg or more weight gain since age 18-20 y • Poor aerobic fitness • Specific races and ethnic groups Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults—The Evidence Report. Obes Res 1998;6(suppl 2).

49. <22 <23 23 - 23.9 24 - 24.9 25 - 26.9 27 - 28.9 29 - 30.9 31 - 32.9 33 - 34.9 35+ Relationship Between BMI and Risk of Type 2 Diabetes Chan J et al. Diabetes Care 1994;17:961. Colditz G et al. Ann Intern Med 1995;122:481. 93.2 Men Women 54.0 Age-Adjusted Relative Risk 42.1 40.3 27.6 21.3 15.8 8.1 5.0 11.6 4.3 2.9 2.2 6.7 4.4 1.5 1.0 1.0 1.0 Body Mass index (kg/m2)

50. Lifestyle: Weight Management Modest weight loss has been shown to reduce insulin resistance Lifestyle modifications should be the primary approach to weight loss. Physical activity and behavior modification are important components of weight loss programs and are helpful in maintenance of weight loss. Fat intake should be <7% of total calories Monitoring carbohydrates remains a key strategy in achieving glycemic control. Sugars and nonnutritive sweeteners are safe if consumed within the acceptable daily intake levels.