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Diabetes Mellitus: Management Options

Diabetes Mellitus: Management Options. John E. Sutherland, M.D. University MD-PhD Educators January 2003. This module is supported by an unrestricted educational grant from Aventis Pharmaceuticals Education Center. Criteria for the diagnosis of diabetes.

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Diabetes Mellitus: Management Options

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  1. Diabetes Mellitus: Management Options John E. Sutherland, M.D. University MD-PhD Educators January 2003 This module is supported by an unrestricted educational grant from Aventis Pharmaceuticals Education Center

  2. Criteria for the diagnosis of diabetes 1. Symptoms of diabetes and a casual plasma glucose ≥200 mg/dl (11.1 mmol/l). Casual is defined as any time of day without regard to time since last meal. The classic symptoms of diabetes include polyuria, polydipsia, and unexplained weight loss. OR 2. FPG ≥126 mg/dl (7.0 mmol/l). Fasting is defined as no caloric intake for at least 8 hours

  3. Criteria for the diagnosis of diabetes (con’t) 3. 2-h PG ≥ 200 mg/dl (11.1 mmol/l) during an OGTT. The test should be performed as described by the World Health Organization, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.

  4. Criteria for testing for diabetes in asymptomatic adult individuals • Testing for diabetes should be considered in all individuals at age 45 years and above and, if normal, it should be repeated at 3-year intervals. • Testing should be considered at a younger age or be carried out more frequently in individuals who: • Are obese (≥ 120% desirable body weight or a BMI ≥ 27 kg/m2) • Have a first-degree relative with diabetes • Have delivered a baby weighing > 9 lb or have been diagnosed with GDM

  5. Criteria for testing for diabetes in asymptomatic adult individuals (con’t) • Are members of a high-risk ethnic population (e.g., African-American, Latino, Native American, Asian-American, Pacific Islander) • Are hypertensive (≥ 140/90 mmHg) • Have HDL cholesterol level ≤35 mg/dl (0.90 mmol/l) and/or a triglyceride level ≥ 250mg/dl (2.82 mmol/l) • On a previous testing, had IGT or IFG • Have other clinical conditions associated with insulin resistance (e.g., PCOS or acanthosis nigricans)

  6. Mean HbA1c = 11% 10% 9% 8% 7% DCCTRisk of Sustained Retinopathy Progressionby HbA1c and Years of Follow-up 24 20 Rate per100 person-years 16 12 8 4 0 0 1 2 3 4 5 6 7 8 9 Time during study (years) DCCT. Diabetes. 1995;44:968-983.

  7. DCCT FINDINGS Lowering Blood Sugar Reduces Risk of: • Eye disease 76% • Kidney disease 50% • Nerve disease 60% • Cardiovascular disease 35%

  8. UKPDS • Similar reduction with Type II Diabetes Mellitus • Moderate reductions in hypertension and dyslipidemia • Significantly improved outcomes • 11% reduction in MIs with each 10mm Hg  in SBP

  9. HbA1c • Best determinant of glycemic exposure • Mean is a quality indicator

  10. Glycemic control for nonpregnant individuals with diabetes Additional action suggested Normal Goal

  11. % HbA1c Average Glucose (mg/dL) 4 60 5 90 6 120 7 150 8 180 9 210 10 240 11 270 12 300

  12. Biguanides Decrease Hepatic Glucose Production Sulfonylureas and Nonsulfonylurea Secretagogues Increase Insulin Secretion TZDs Decreased Lipolysis Thiazolidinedinones (TZDs) Increase Glucose Uptake TZDs Adipose Tissue Increased Lipolysis Liver Increased Glucose Production Pancreatic Beta Cells Decreased Insulin Secretion Skeletal Muscle Decreased Glucose Uptake Increased Free Fatty Acids Lipotoxicity Lipotoxicity Defective Insulin Secretion Insulin Resistance Glucotoxicity a-Glucosidase Inhibitors Delay Intestinal Carbohydrate Absorption Hyperglycemia Small Intestine Carbohydrate Absorption

  13. Options for monotherapy Sulfonylureas Meglitinides Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  14. Target Population Sulfonylureas Meglitinides • Recent type 2 DM diagnosis • Type 2 DM < 5 years’ duration Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  15. Target Population Sulfonylureas Meglitinides • Recent type 2 DM diagnosis • Elevated PPG Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  16. Target Population Sulfonylureas Meglitinides • Overweight/ obese • Insulin resistant Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  17. Target Population Sulfonylureas Meglitinides • Insulin resistant • Overweight/ obese Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  18. Target Population Sulfonylureas Meglitinides • Elevated PPG • Contraindications to other agents Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  19. Advantages Sulfonylureas Meglitinides • Rapid FPG reduction • Low cost Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  20. Advantages Sulfonylureas Meglitinides • ↓Risk of hypoglycemia • Short-acting • Meal-adjusted dosing Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  21. Advantages Sulfonylureas Meglitinides • No weight gain • ↓ Risk of hypoglycemia Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  22. Advantages Sulfonylureas Meglitinides • ↓Amount of insulin • ↓Risk hypoglycemia Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  23. Advantages Sulfonylureas Meglitinides Biguanides • ↓ Risk ofhypoglycemia • Non systemic action Thiazolidinediones Alpha-glucosidase inhibitors

  24. Disadvantages Sulfonylureas Meglitinides • Weight gain • ↑ Risk of hypoglycemia Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  25. Disadvantages Sulfonylureas Meglitinides • ↓High costs • Frequent dosing Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  26. Disadvantages Sulfonylureas Meglitinides • GI side effects • High costs • Rare lactic acidosis Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  27. Disadvantages Sulfonylureas Meglitinides • High cost • Weight gain • Slow onset of action • Issue of liver toxicity Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  28. Disadvantages Sulfonylureas Meglitinides • High cost • GI side effects Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  29. Total daily dose (mg) & dosing interval Sulfonylureas Meglitinides • Glyburide 1.25 to 20 QD or BID • Glyburide, micronized 0.75 to 12 QD or BID • Glipzide 2.5 to 40 QD or BID • Glipizide, extended-release 2.5 to 20 QD • Glimepiride 1 to 8 QD Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  30. Total daily dose (mg) & dosing interval Sulfonylureas Meglitinides Biguanides • Nateglinide 180 to 360 TID • Repaglinide 1.5 to 16 TID or QID Thiazolidinediones Alpha-glucosidase inhibitors

  31. Total daily dose (mg) & dosing interval Sulfonylureas Meglitinides Biguanides • Metformin HCI 1,000 to 2,550 BID or TID • Metformin, extended-release 1,000 to 2,000 QD or BID Thiazolidinediones Alpha-glucosidase inhibitors

  32. Total daily dose (mg) & dosing interval Sulfonylureas Meglitinides • Rosiglitazone maleate 4 to 8 QD or BID • Pioglitazone HCI 15 to 45 QD Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  33. Total daily dose (mg) & dosing interval Sulfonylureas Meglitinides • Acarbose 150 to 300 TID • Miglitol 150 to 300 TID Biguanides Thiazolidinediones Alpha-glucosidase inhibitors

  34. Monotherapy Pearls • All drugs except AGIs and nateglinide equally reduce HbA1c • Metformin usually best for obese- no weight gain • Non-SU secretagogues may be useful for irregular meals • Metformin and TZDs avoid hypoglycemia

  35. Clinical Efficacy of Oral Hypoglycemic Agents

  36. Options for combination therapy Sulfonylureas + Biguanide Or ThiazolidinedioneOr Alpha-glucosidase inhibitor Biguanide + Alpha-glucosidase inhibitor Biguanide + meglitinide Triple combination therapy Sulfonylurea + biguanide + Thiazolidinedione or Sulfonylurea + biguanide + alpha-glucosidase inhibitor Biguanides + Thiazolidinediones If therapeutic goals are not met using the above combinations; switch to insulin +/- oral agent

  37. Insulin Therapy in Type 2 DM • Not 1st line, except initially in some • 50% need eventually • ↓ gluconeogenesis and ↑ glucose uptake • Can be combined with oral agents

  38. Insulin Options: Long and Intermediate NPH Lente Ultralente Glargine

  39. Short-acting Insulin Options Regular Lispro Aspartine

  40. Combination Insulin Options • 70 NPH/30 Reg premixture • 50 NPH/50 Reg premixture • 75 lispro protamine/25 lispro

  41. IDC Insulin Staged Regimens OA – O – O – N R/N – O – R/N – O R/N – O – R – N R – R – R – N

  42. BID Insulin Division AMPM Distribution 2/3 1/3 R/N Ratio 1:2 1:1 Premix: Best for drawing impaired

  43. Insulin Therapy Profiles • Variable absorption of NPH, Lente, Ultralente • Peak effect late with regular • Split/mixed insulin hypoglycemia • Lantus more predictable absorption • Humalog/Novolog more rapid peak/fall

  44. Multiple Dose Insulin Intensive Therapy • Basal dose suppresses hepatic glucose output • Bolus dose enhances postprandial glucose uptake • Basal dose about 50% • Bolus doses 10-20% before meals

  45. Premeal Humalog or Novolog Insulin • CHOgm intake/carbohydrate insulin ratio (CIR) • CIR= 500 TDD • TDD (total daily dose) = BW (lb) 4 • Common ratio: 1u/5-15 gms CHO • Correction Dose = 1800 /TDD = 1u ↓ of BG mg/dl • Ideal BG rise post meal is 30 – 60 mg • Out of Target adjustment range 1 u/30-50 BG mg/dl

  46. Diabetes Self-Management Skills Medical Nutrition Therapy, Activity Patient Education, Glucose Monitoring Hyperglycemia Insulin Resistance Other Components of Care Hypertension Lipid Disorders Micro vascular Complications Hemoglobin A1c (2 – 4 times per year) Target ≤ 7.0% SMBG 80-140 mg/dL (-50% of readings) Combination RX Insulin Therapy Insulin Sensitizers

  47. Diabetes Self-Management Skills Medical Nutrition Therapy, Activity Patient Education, Glucose Monitoring Hyperglycemia Insulin Resistance Other Components of Care Hypertension Lipid Disorders Micro vascular Complications GOALS LDL < 100 mg/dL Annual Lipid Profile Trigs < 150 mg/dL HDL > 45 mg/dL♂ Statin Therapy > 55 mg/dL♀ Fibrate Therapy ? Glitazones

  48. Clinical Approaches to the Treatment of Dyslipidemia in Patients with Diabetes

  49. Diabetes Self-Management Skills Medical Nutrition Therapy, Activity Patient Education, Glucose Monitoring Hyperglycemia Insulin Resistance Hypertension Other Components of Care Lipid Disorders Micro vascular Complications Blood Pressure (every visit) Dx and Rx + 130/80 mm Hg ACEI-Based Therapy Combination Rx

  50. Blood Pressure Management(every visit)Diagnosis and Rx Target < 130/80 mm Hg Nonpharmacologic Therapies Weight management Physical activity Sodium restriction Smoking cessation Hypertension Normal BP ↑ CVD Risk Hypertension with Nephropathy ACE Inhibitor Target BP < 130/80 mm Hg ACE Inhibitor or ARB Target BP < 130/80 mm Hg ACE Inhibitor or ARB Target BP < 125/75 mm Hg Consider multidrug therapy (required in up to 60% of patients) Thiazide Low cost Systolic HTN Elderly patients Β-Blocker Effective post-MI Avoid if severe hypoglycemia Ca++ Channel Blocker Systolic HTN ? Non DHP Use in combination Other Agents Consider cost Use in combination

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