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New Perspectives in the Management of Type 2 Diabetes

New Perspectives in the Management of Type 2 Diabetes. Herold Merisier, MD, FAAFP Voluntary Assistant Professor of Family Medicine Miller School of Medicine, University of Miami Plantation, FL. Disclosure. Speaker: Novartis Pharmaceuticals Speaker: Novo-Nordisk. Diabetes 2010.

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New Perspectives in the Management of Type 2 Diabetes

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  1. New Perspectives in the Management of Type 2 Diabetes Herold Merisier, MD, FAAFP Voluntary Assistant Professor of Family Medicine Miller School of Medicine, University of Miami Plantation, FL

  2. Disclosure • Speaker: Novartis Pharmaceuticals • Speaker: Novo-Nordisk

  3. Diabetes 2010 • Epidemiology • Diagnosis • Screening • Management of Type 2 Diabetes • Patient Education • Therapeutic Lifestyle Changes (TLC) • Pharmacotherapy • Treatment of co-morbid conditions

  4. Diabetes in the US • 23.6 million children and adults affected (7.8% of the population) • Diagnosed: 17.9 million people • Undiagnosed: 5.7 million people • 1.6 million new cases in adults > 20y/o in 2007 • 4300 new cases every day • Pre-Diabetes: 57 million people • 2-4 fold increase in cardiovascular mortality and stroke Center for Disease Control and Prevention Available at: http://www.cdc.gov/diabetes/pubs/estimates07.htm#1

  5. Diabetes in Canada • 1.8 million adults with Diabetes • Prevalence: 4.8% (1998): 1 054 000 adult Canadians • Prevalence: 5.5% (2005) Available at: http://www.diabetes.ca/files/cpg2008/cpg-2008.pdf

  6. Global Projections for the Diabetes Epidemic: 2003-2025 NA EUR 23.0 M 36.2 M ↑57.0% 48.4 M 58.6 M ↑21% EMME WP 19.2 M 39.4 M ↑105% SEA 43.0 M 75.8 M ↑79% 39.3 M 81.6 M ↑108% AFR SACA 7.1M 15.0 M ↑111% World 2003 = 194 M 2025 = 333 M ↑ 72% 14.2 M 26.2 M ↑85% 2003 2025 M = million, AFR = Africa, NA = North America, EUR = Europe, SACA = South and Central America, EMME = Eastern Mediterranean and Middle East, SEA = South-East Asia, WP = Western Pacific Diabetes Atlas Committee. Diabetes Atlas 2nd Edition: IDF 2003.

  7. Diagnosis IFG: Impaired Fasting Glucose FPG: Fasting Plasma Glucose RPG: Random Plasma Glucose IGT: Impaired Glucose Tolerance PPG: Post-Prandial Glucose Adapted from Clinical Practice Recommendations. Diabetes Care, 2010

  8. Screening • All individuals ≥ 45y/o, particularly if BMI ≥ 25 • if normal, repeat every 3 years • Start screening at younger age if BMI ≥ 25 and: • physically inactive • first-degree relative with Diabetes • high risk ethnic group • h/o IFG, IGT, Gestational Diabetes, PCOS • Dyslipidemia or h/o cardio-vascular disease • Fasting glucose or 2-hour OGTT • Diabetes Risk Calculator

  9. Diabetes Risk Calculator • Gender • Age • Prior history of elevated blood glucose • Height and weight • Diet • Smoking history • Physical activity • Family history Diabetes Care. 2008 May;31(5):1040-5

  10. Diabetes Risk Calculator Available at: http://www.diabetes.org/diabetes-basics/prevention/diabetes-risk-test/

  11. Diabetes Risk Calculator Available at: http://www.diabetes.org/diabetes-basics/prevention/diabetes-risk-test/

  12. QD Score (http://www.qdscore.org) BMJ 2009;338:b880. Available at: http://bmj.com/cgi/content/full/338/mar17_2/b880

  13. Management of Type 2 Diabetes • Patient Education • Therapeutic Lifestyle Changes (TLC) • Pharmacotherapy • Treatment of co-morbid conditions

  14. Pharmacotherapy: Oral Agents

  15. DPP-4 Inhibitors

  16. Rosiglitazone (Avandia®) • Contraindicated in patients with CHF • Meta-analysis of 42 clinical studies: • Mean duration 6 months; 14,237 total patients • Rosiglitazone vs. placebo • Increased risk of risk of myocardial ischemic events • Three other studies • Mean duration 41 months; 14,067 total patients • Rosiglitazone vs. other oral diabetes medications or placebo • Increased of MI neither confirmed nor excluded this risk

  17. Diagnosis Progressive -cell Failure in Type 2 Diabetes 100 80 60 -cell Function (% ) 40 20 0 -12 12 -6 0 6 Years Based on data of UKPDS 16: conventional (diet) treatment group. Diabetes. 1995.

  18. Pharmacotherapy: Non-Insulin Injectables

  19. Pharmacotherapy: Insulin(Older Agents)

  20. Pharmacotherapy: Insulin(Newer Agents: Insulin Analogs)

  21. Pancreas ↑Sulfonylureas↑Repaglinide TZD Adipose tissue Glucose Gut ↓ Glucose uptake ↓α-Glucosidase inhibitors Hyperglycemia Rosiglitazone Pioglitazone Acarbose Miglitol ↑HGO* Liver Muscle ↑Metformin ↑Thiazolidinediones ↑Metformin ±Thiazolidinediones Therapy for Type 2 Diabetes: Sites of Action *HGO=hepatic glucose output. Adapted from DeFronzo RA. Ann Intern Med. 1999;131:281-303.Package Inserts for AVANDIA® (rosiglitazonemaleate, GlaxoSmithKline), Actos® (pioglitazoneHCl, Takeda), Prandin® (repaglinide, Novo Nordisk), Precose® (acarbose tablets, Bayer), Glyset® (miglitol, mfd. by Bayer for Pharmacia & Upjohn).

  22. Stepwise Management of Type 2 Diabetes Insulin Oral plus insulin + + Oral combination + Oral monotherapy Diet & exercise Adapted from Williams G. Lancet 1994; 343: 95-100.

  23. PharmacotherapyStepwise Management • Glycemic targets often not met • Monotherapy often not effective long term • Therapy fails to address multiple impairments • Step-wise approach tends to perpetuate “failure”

  24. New Treatment Paradigm • Treatment designed to address multiple impairments • Simultaneous rather than sequential therapy • Combination therapy from the outset • Early titrations to meet glycemic targets

  25. Combination Oral Diabetic Agents • Glucovance® ( Glyburide + Metformin) • Metaglip® (Glipizide + Metformin) • Avandamet® (Rosiglitazone + Metformin) • Avandaryl® (Rosiglitazone + Glimepiride) • ActoPlus Met® (Pioglitazone + Metformin) • Janumet® (Januvia + Metformin)

  26. Tier 2: Less well validated therapies Step 1 Lifestyle + Metformin + Pioglitazone + Sulfonylurea Step 2 Step 3 Lifestyle + Metformin + Pioglitazone Tier 1: Well-validated core therapies At Diagnosis Lifestyle + Metformin Lifestyle + Metformin + Intensive Insulin Lifestyle + Metformin + Basal Insulin Lifestyle + Metformin + GLP1- Agonist Lifestyle + Metformin + Basal Insulin Lifestyle + Metformin + Sulfonylurea • ADA/EASD Consensus Algorithm 2009 Nathan and Associates: Diabetes Care, Vol. 32, Number 1, January 2009

  27. ACCE Diabetes Algorithm 2009 Glycemic Control Algorithm, EndocrPract. 2009;15(No. 6)

  28. Glucose Dynamics: Basal andPrandial 250 Postprandial hyperglycemia 200 Type 2diabetes Plasma glucose (mg/dL) 150 Basal hyperglycemia 100 50 Normal 0 0600 1200 1800 2400 0600 Time of day Riddle MC. Am J Med. 2004;116(suppl):3S-9.

  29. Bolusinsulin Bolusinsulin Basalinsulin Bolusinsulin Basal-Bolus Combination Therapy Breakfast Lunch Dinner Plasma Insulin Levels 4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00 Time

  30. Treatment of co-morbid conditions • Dyslipidemia • Hypertension

  31. Diabetes CV Risk Calculator Available at: http://www.dtu.ox.ac.uk/riskengine/

  32. Diabetes CV Risk Calculator (Canada) http://www.diabetes.ca/documents/about-diabetes/FINAL_PATIENT_TOOL_FOR_WEBSITE.pdf

  33. The ABCs of Diabetes Care • A1C • ADA recommends < 7% in general, < 6% for selected individuals • AACE/IDF recommend ≤ 6.5% • Blood pressure • < 130/80 mm Hg • Cholesterol • LDL-C: < 100 mg/dL (< 70 mg/dL in very high-risk patients) • HDL-C: > 40 mg/dL in men and > 50 mg/dL in women • Non-HDL-C: < 130 mg/dL (< 100 mg/dL in high-risk patients) • Triglycerides: < 150 mg/dL American Diabetes Association. Diabetes Care. 2007;30(suppl 1):S4-S41. American Association of Clinical Endocrinologists. EndocrPract. 2007;13(suppl 1):3-68. International Diabetes Federation. Diabet Med. 2006;23:579-593.

  34. Additional Recommendations • Individualized Medical Nutrition Therapy • Exercise • Aspirin (75-325 mg/d) • Smoking cessation • Screening for microvascular complications (eyes, kidneys, feet) • Immunization ( Flu vaccine, Pneumovax) • Recommended cancer screening

  35. Optimal Care of the Diabetic Patient Aggressive Rx forCV risk reduction Intensive glycemic control Lifestyle interventions • Dyslipidemia: Statin • Hypertension: ≥2 drug classes, include ACEI or ARB • Microalbuminuria:ACEI or ARB • Use of aspirin • CHD: ACEI, β-blocker • CVD/high risk: ACEI • Proper nutrition • Physical activity program • Smoking cessation • Weight control • HbA1c <7% • Glucose (mg/dL):Preprandial 90–130Postprandial <180 ADA. Diabetes Care. 2005;28(suppl 1):S1-79.

  36. Thank You For Your Attention

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