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Type II Diabetes

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By James A. Yost, MD, MS, MBA Emory Family Medicine Type II Diabetes

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OBJECTIVES: INTRODUCTION EPIDEMIOLOGY GENETIC SUSCEPTIBILITY PHYSIOLOGY PATHOPHYSIOLOGY SCREENING DIAGNOSIS COMPREHENSIVE DIABETES EVALUATION MEDICAL NUTRITION THERAPY GOALS OF THERAPY TREATMENTS Type II Diabetes

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Introduction: Type 2 diabetes mellitus is characterized by hyperglycemia, insulin resistance, and relative impairment in insulin secretion It is a common disorder with a prevalence that rises markedly with increasing degrees of obesity Type II Diabetes

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Epidemiology: Approximately 18.2 million individuals (6.3% of the US population), have diabetes From 1990 to 1998, the prevalence increased 33% The projected prevalence increase is165% by 2050 The economic burden attributable to diabetes was estimated to be $132 billion in 2002 Type II Diabetes

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Genetics: 2 – 6 times more prevalent in African Americans, Native Americans, Pima Indians, and Hispanic Americans in the United States than in whites 39% of patients have at least one parent with the disease Among monozygotic twin pairs with one affected twin, approximately 90 percent of unaffected twins eventually develop the disease Type II Diabetes

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Physiology: Type II Diabetes

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Type II Diabetes amylin Induces satiety

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Physiology: GLP-1 Secreted by L-cells in the proximal small gut Triggers satiety Stimulates the pancreas to secrete insulin Turns off glucagon Prevents hypoglycemia Degraded by DPP4 Amylin: Second ß-cell hormone that is normally co-secreted with insulin in response to meals Suppression of postprandial glucagon secretion Decreases gastric emptying Type II Diabetes

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Pathophysiology: Multifactorial process that occurs over an extended time genetic lifestyle cultural environmental factors Obesity is the most common risk factor Type II Diabetes

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Screening: Type II Diabetes

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Diagnosis: FPG >126 mg/dL on 2 or more occasions The presence of diabetic symptoms plus a casual plasma glucose concentration >200 mg/dL on 2 or more occasions A 2-hr post load glucose >200 mg/dL during an OGTT (the glucose load should be 75 g anhydrous glucose dissolved in water) Type II Diabetes

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Diagnosis: Impaired Fasting Glucose FPG <100 mg/dL = normal fasting glucose FPG from 100 to 125 mg/dL = impaired fasting glucose FPG >126 mg/dL = provisional diagnosis of diabetes Impaired Glucose Tolerance 2-hr 75-g OGTT <140 mg/dL = normal glucose tolerance 2-hr 75-g OGTT from 140 to 199 mg/dL = impaired glucose tolerance 2-hr 75-g OGTT >200 mg/dL = provisional diagnosis of diabetes Type II Diabetes

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Comprehensive Diabetes Evaluation: Medical History Symptoms Eating patterns, nutritional status, and weight history Exercise history Medications Risk factors for atherosclerosis smoking, hypertension, obesity, dyslipidemia, and family history Physical Examination Head to toe Must include monofilament exam Type II Diabetes

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Type II Diabetes

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Comprehensive Diabetes Evaluation: Initial Laboratory Evaluation Hemoglobin A1C Fasting lipids U/A Microalbuminuria (yearly) BUN/Cr (Yearly) TSH (Yearly) EKG (Yearly) Anti-GAD antibodies (Once) (Type 1 DM) C-peptide level (yearly for 5 years) Every Visit Labs FBS A1C every 3 months or fructosamine every 2-3 weeks U/A Type II Diabetes

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Comprehensive Diabetes Evaluation: Referrals Eye examination (yearly) Medical Nutrition therapy (at lease once) Podiatry (yearly) Type II Diabetes

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Type II Diabetes

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Type II Diabetes

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Medical Nutrition Therapy Can achieve >2% reduction in A1C within the 1st year according to the United Kingdom Prospective Diabetes Study (UKPDS) Type of CHO doesn’t matter, it’s the amount 1 CHO serving = 15 g CHO Limit to 3-4 servings per meal, 1-2 servings per snack Limit to 1800 to 2000 cal per day Type II Diabetes

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Goals of Therapy Type II Diabetes

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Treatment: Six classes of oral agents for treatment of type 2 diabetes biguanides sulfonylureas meglitinides Thiazolidinediones alpha-glucosidase inhibitors DPP-4 inhibitors Two classes of non-insulin injections Amylin analogs GLP-1 analogs Type II Diabetes

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Biguanides: Actions: Decrease Gluconeogenesis and increases insulin sensitivity Recommended initial medical therapy in almost all Type 2 pts. Decrease A1C by 1-2. Advantage: No hypoglycemia Metformin (Glucophage): 500 mg PO q day then up to 1000 mg PO bid Avoid use in situations where lactic acidosis is more likely. Liver disease. Renal insufficiency (Cr >1.5 male / Cr >1.4 female) Type II Diabetes

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Sulfonylureas: Increase insulin secretion by stimulating beta cell function of the pancreas Decrease A1C by 1-2. Glipizide (Glucotrol) 2.5 mg PO q day (start), 20 mg PO bid (max) Glyburide (Micronase) 2.5 mg PO q day (start), 20 mg PO q day (max) Glimepizide (Amaryl) 1 mg PO q AM 8 mg PO q day (max) Biggest risk is hypoglycemia. Type II Diabetes

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Meglitinides Similar but unrelated to sulfonyureas. Increase insulin secretion by stimulating beta cell function of the pancreas No distinct advantage, increased dosing frequency and increased cost Short half life Nateglinide (Starlix) 60 mg PO tid (before meals) Repaglinide (Prandin) 0.5 mg PO tid (before meals) Type II Diabetes

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Thiazodiolidinediones (TZD’s) PPARg agonist. This action leads to increased insulin sensitivity in peripheral tissues. A1C lowering of 1-1.5. Pioglitazone (Actos) 15 mg PO q day (start), 45 mg PO q day (max) Rosiglitazone (Avandia) 2 mg PO q day (start) 8 mg PO q day (max) Advantage of class is ability to dose in renal insufficiency. Disadvantages are increase in weight / increase peripheral edema / precipitate CHF / lower Hemoglobin / precipitate MI (not shown in randomized trial, but shown in recent meta analysis). Type II Diabetes

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Alpha-glucosidase Inhibitors Reduce absorption of carbohydrates. A1C lowering is modest. 0.5 – 1. Acarbose (Precose) 25 -50 mg PO tid (start) 100 mg PO tid (max) Miglitol (Glyset) 25 mg PO tid (start) 100 mg PO tid (max) Side effects limit effectiveness. Flatulence / Diarrhea. Type II Diabetes

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DPP-IV Inhibitors Dipeptidyl peptidase IV. Enzyme that deactivates GLP-1 and GIP. A1C reduction of 0.5-1.0. Sitagliptin (Januvia) 100 mg PO q day Approved for Type 2 DM. Monotherapy or ideally as add on to metformin or TZD. Advantages: Oral dosing Disadvantages: Cost Renal adjustment required. Type II Diabetes

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Amylin analogs A1C reduction 0.5-1.0 Pramlintide (Symlin) 60 mcg SQ q AC (start DM 2) (15 mcg if DM 1) 120 mcg SQ q AC, (max dose)(60 mcg if DM 1) Only approved as add-on to insulin. Advantages: Mild weight loss. No dose adjustment needed with kidney / liver dysfunction. Can use in DM 1 or DM 2. Disadvantages: Nausea, usually resolves. Hypoglycemia if insulin dose not adjusted Decrease rapid acting insulin dose by 50% when starting pramlintide. Type II Diabetes

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GLP-1 analogs Slows gastric emptying decreases post meal glucagon pulse decrease appetite A1C reduction of 1 Exenatide (Byetta) 5 mcg SQ bid up to 1 hour before AM and PM meals 10 mcg SQ bid up to 1 hour before AM and PM meals (max) Advantages: Weight loss Disadvantages: Nausea, cost, SQ dosing Type II Diabetes

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Treatment Insulin Therapy Short acting insulins regular (Humulin R) lispro (Humalog) aspart (NovoLog) Glulisine (Apidra) Long acting insulins NPH insulin (Novolin N) Detemir insulin (Levemir) Glargine insulin (Lantus) Inhaled insulin Exubera 0.05 mg/kg inhaled tid (immediately prior to meals) 1 mg = 3 units regular insulin 3 mg = 8 units regular insulin Type II Diabetes

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Insulin Therapy added to Oral Agents When adding to oral agents, continue current dose but D/C sulfonylureas and decrease dose TZDs Start basil bolus at approx. 10 units QHS Increase dose by 2-3 units every 2-3 days to achieve FBS in AM of <110 mg/dl Decrease dose by 2-3 units every 2-3 days if FBS <70 mg/dl Type II Diabetes

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Insulin Therapy Only Best is basil plus prandial insulin Determine total daily dose (TDD) Start with 0.4 units/kg Add 0.1 unit/kg for each of the following: BMI > 40 New Diabetic with BG > 300 Known Diabetic with BG > 200 Subtract 0.1 unit/kg if > 75 y/o If GFR 10-50, reduce TDD to 50% of calculated If GFR <10, reduce TDD to 75% of calculated Type II Diabetes

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A patient presents with symptoms of polyuria, polyphagia, and polydipsia. Which of the following casual plasma glucose levels meets the criteria for a diagnosis of diabetes? A. 111 mg/dL. B. 134 mg/dL. C. 152 mg/dL. D. 183 mg/dL. E. 200 mg/dL. Questions

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Because of the correlation between mean plasma glucose and hemoglobin (Hb) A1c levels, the American Association of Clinical Endocrinologists recommends an HbA1c goal of: A. Less than 7.5%. B. Less than 7%. C. Less than 6.5%. D. Less than 6%. E. Less than 5.5%. Type II Diabetes

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You are establishing goals for diabetes control with an extremely motivated 39- year-old woman with type 2 diabetes. According to the American Association of Clinical Endocrinologists, the pre-prandial plasma glucose goal should be: A. Less than 90 mg/dL. B. Less than 100 mg/dL. C. Less than 110 mg/dL. D. Less than 120 mg/dL. E. Less than 130 mg/dL. Type II Diabetes

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Which of the following oral antidiabetic agents does not cause hypoglycemia when given alone? A. Metformin. B. Acarbose. C. Repaglinide. D. Glyburide. Type II Diabetes

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Which of the following antihypertensive drugs is recommended for reducing the progression to macroalbuminuria in a patient with diabetes? A. Angiotensin receptor blocker. B. Thiazide diuretic. C. Beta blocker. D. Calcium channel blocker. Type II Diabetes

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According to the Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III), a 41-year-old patient with diabetes, who does not have coronary artery disease, should be treated to a low-density lipoprotein cholesterol goal of: A. Less than 200 mg/dL. B. Less than 150 mg/dL. C. Less than 100 mg/dL. D. Less than 70 mg/dL. E. Less than 50 mg/dL. Type II Diabetes

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American Diabetic Association. Diabetic care 2007;31 (S1) Diabetes Prevention Program Research Group. N. Eng J Med 2002;346:393 American Association of Clinical Endocrinologist www.aace.com/pub/pdf/guidelines/DMGuidelines2007.pdf American Academy of Family Physicians www.aafp.org/online/en/home/cme/selfstudy/videocme/diabetes.html Association of Family Medicine Residency Program directors Frontline Diabetic Workshop References

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