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  1. Hyperlipidemia Management in T2DMChanging Diabetes Mellitus to Diabetes LipidusDr.Wehad ALTourahConsultant Internist, Assistant Director Internal Medicine Residency training ProgramFRCP(London),KBIMAmiri Hospital

  2. Outline Cases Epidemiology and cardiovascular risk Lipid pattern & Target in T2DM Screening CV Risk Stratification Treatment Options: Statins,Fibrates,Niacin,Ezetimibe,Omega-3 FA Combination Treatment Drug Monitoring Statin and DM Future Research Conclusion

  3. Case 1 45 years-old gentleman T2DM for 3 years, No other significant history Med.: Metformin 1gm /BID BMI 30 Bp 120/80 Total Cholesterol 7mmol/L LDL-C:2.6 mmol/L HDL-C:1.0 mmol/L TG: 2.0 mmol/L

  4. Case1 What will be your primary lipid target : LDL-C? HDL-C? TG?

  5. Case 2 45 years- old gentleman Current smoker,T2DM for 5 years, hypertension for 10 years He is on lisonpril 10mg OD, metformin 1 gm BID BMI 28 Blood pressure: 135/85 mmHg HA1C 6.5% Total cholesterol: 5 mmol/L LDL-cholesterol: 2.6 mmol/L HDL-cholesterol: 1.2 mmol/L Triglycerides: 2.0 mmol/L

  6. Case 2 Would You Initiate a lipid lowering agent in This Patient? OR Would you advise non-pharmacological Treatment?

  7. Case 3 50 years-old lady T2DM for 12 years, Hypertension, non-smoker Meds: metformin 1gm BID, lisinopril 20mg/day, simvastatin10mg/day BMI 26.5 Bp: 135/85 mmHg Total cholesterol: 4.7 mmol/l LDL-cholesterol: 2.7 mmol/L HDL-cholesterol: 1.0 mmol/L Triglycerides: 2.4 mmol/L

  8. Case 3 Would you Intensify This Patient’s Statin? OR Would you change her statin to more potent agent?

  9. Case 4 65year-old lady, T2DM, PCI for STEMI 6 months ago no current CV symptoms Meds: ASA, clopidogrel, lisinopril, atorvastatin 80 mg/day BMI 29.0 Blood pressure: 125/85 mmHg Total cholesterol: 3.1 mmol/L LDL-cholesterol: 0.9 mmol/L HDL-cholesterol: 0.9 mmol/L Triglycerides: 3.4 mmol/L

  10. Case 4 Would you decrease this patient’s statin dose? ORWould you add a fibrate?

  11. Case 5 50 year-old lady T2DM 5 years, Hypertension 5 years Had pain in her arms and legs for 6 months Meds: Lisinopril 10mg/d, atorvastatin 20mg/d, aspirin 75mg/d LFT:N CK:700 (40-176 IU/L) Total cholesterol:4.0mmol/L LDL-C:1.8mmol/L HDL-C:0.9mmolL TG:2.0mmol/L

  12. Case 5 What will be your Approach to Solve this patient’s problem?

  13. DM is a Huge Burden IDF Diabetes Atlas, 6th edition

  14. Top 10 countries/territories for prevalence(%) of diabetes (20-79),2013

  15. Dm and CVD IDF 2013 Dm is Strong risk Factor for CAD:DM=CHD T2DM is associated with a marked risk of CVD. Individuals with DM have an absolute risk of major coronary events similar to that on nondiabetic individuals with established coronary heart disease Medescape.Treating Dyslipidemia: Recommendations for T2DM 27/9/13

  16. The risk for CVS death is ↑2-3 fold in T2DM.

  17. Prevalence of Dyslipidemia is high in Type 2 Diabetes N = 498 adults (projected to 13.4 million) aged > or = 18 years with diabetes representative of the US population and surveyed within the cross-sectional National Health and Nutrition Examination Survey 1999-2000. Diabetes Res Clin Pract;70:263-269.2005

  18. Lipid Pattern in Diabetes UKPDS

  19. Lipid Pattern in Diabetes UKPDS Clinical Diabetes.Vol.24,no.1,2006

  20. The relationship between LDL-C,HDL-C and CVD UKPDS,0.1mmol/L ↑HDL-C was associated with 15% ↓in CVD events UKPDS,1mmol/L ↑LDL-C was associated with 57% ↑risk MI adapted from Gordon T. et al, American Journal of Medicine, 1977;62;707-714

  21. Lipid Pattern in Diabetes

  22. Lipoprotein Pattern in Diabetes Diabetes Care.16:434-444.1994

  23. Whom to Screen?How often?

  24. ADA Guidelines 2014 -In most adult patients with DM, measure fasting LIPID PROFILE AT LEAST ANNUALLY. (LEVEL B) -In adults with low risk lipid values(LDL-C <2.6mmol/L, HDL-C>1.3mmol/L, and TG<1.7mmol/L),LIPID ASSESSMENT MAY BE REPEATED EVERY 2 YEARS.(Level E) Diabetes Care,volume 37,Supp 1,January 2014

  25. What are the additional predictors beyond LDL and HDL To be assessed? 1-Apo lipoprotein B: No evidence yet for regular screening. Very strong predictor for cardiovascular disease in DM. Has less biologic variation, reliable measures. Non fasting sample. High cost. ESC/EAS 2011

  26. What are the additional predictors beyond LDL and HDL to be assessed? 2-Highly sensitive CRP -These additional inflammatory markers are helpful in intermediate risk patients but proven to be unhelpful for the very high risk patients.

  27. Risk Stratification?Is it important? What are the risk scoring systems?

  28. Total cardiovascular risk estimation 1- Framingham Risk Score. 2- Systemic Coronary Risk Estimation(SCORE). 3-Atherosclerotic cardiovascular disease risk (ASCVD).(ACC/AHA) 4- QRISK Lifetime cardiovascular risk (Joint British Societies in 2014).

  29. SCORE Framingham Risk Score

  30. Total cardiovascular risk estimation ESC/EAS Guidelines 2011

  31. ASCVD 10-year Risk ACC/AHA Guidelines 2013

  32. Cumulative Incidence of CVD Adjusted for the Competing Risk of Death According to Risk Factor Burden at Age 50 Lloyd-Jones DM et al, Circulation 2006;113:791

  33. Management of Hyperlipidemia in DM?

  34. Management Of Hyperlipidemia in T2DM? 1-Whom should we treat? 2-What are the important targets? 3-What are the target Levels? 4-What are the treatment Strategies?

  35. Q1: Whom Should we Treat?

  36. Whom Should we Treat?ADA Guidelines 2014 1-Diabetic patients <40years,without CVD,LDL cholesterol>2.6mmol/L(low risk) after failure of life style modifications, or with multiple CVD risk factors(level C). ADA Guidelines, January 2014

  37. Whom Should we Treat?ADA Guidelines 2014 2- Patients without CVD,>40years,having one or more other CVD risk factors(family history of CVD, hypertension,smoking,albuminuria) regardless of the LDL(level A). 3-Diabetic patients with overt CVD, regardless of the LDL level(High risk patients),(level A). ADA Guidelines,January 2014

  38. Q2:Which target is the most important?

  39. UKPDS - LDL cholesterol was the strongest independent predictor of CHD, followed by HDL.TG level did not predict CHD events. Clinical Diabetes.Vol.24,no. 1,2006

  40. Q3: What Are the Lipid’s Target Level?

  41. ADA Guidelines 2014 In individuals without overt CVD, the goal is LDL-C <2.6mmol/L.(Level B) Individuals with overt CVD, a lower LDL-C goal of < 1.8mmol/L with a high dose statin. (Level B) If maximum tolerated statin therapy, a reduction in LDL-C of 30-40-% from baseline is an alternative goal.(Level B) Diabetes Care,vol.37,Supp 1,January 2014

  42. ADA Guidelines 2014 TG <1.7mmol/L and HDL cholesterol>1.0mmo/L in men and > 1.3mmo/L in women. LDL-C -targeted statin therapy remains the preferred strategy.(Level A) ADA Guidelines,January 2014

  43. Q4:What are the Treatment Options or Strategies?

  44. Treatment Options

  45. Life style modification is critical component >5% weight loss if BMI>25 Level I 30min.moderate physical activity on most days/ wk. Level II Life Style Intervention ESC/EAS 2011

  46. Life Style Intervention Serves up 8,000 calorie burger meal... the equivalent of FIVE DAYS worth of food

  47. Life Style InterventionDiet 1-High polyunsaturated fatty acids diet – saturated fat< 7% of daily calories +↓intake of cholesterol to 200mg/day(Level II). 2-↑the amount of soluble dietary fibers to 10-25g/day(level II). →associated with 5-15% ↓in the LDL-C. 3- limits the carbohydrates to <60% in individuals with ↑TG/ ↓HDL→ short term effect /OR replace the saturated fat with carbohydrates /monosaturated fat(Level I). National Evidence Based Guidelines for the Management of Type 2 Diabetes Mellitus. the Australian Centre for Diabetes Strategies.Part7.2004 ADA.2014

  48. Dietary Recommendationto TC and LDL-C ESC,EAS Guidelines2011

  49. Effects of Drug Therapy and Diet on Lipids TC (mg/dL) 1° Prevention (n=40) 2° Prevention (n=53) * 84% reached NCEP LDL target (<130 mg/dL) † 63% reached NCEP LDL-C target (<100 mg/dL) Barnard RJ, et al. ExerptaMedica Brief Reports. 1997;1112-1114.