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Lipid Disorders and Management in Diabetes

Lipid Disorders and Management in Diabetes. Om P. Ganda MD Joslin Diabetes Center Harvard Medical school Boston, MA. Web-conference, April 8, 2010. MRFIT: Cholesterol and CVD Mortality in Men With Type 2 Diabetes. Age-Adjusted CVD deaths per 10,000 person-years. 280.

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Lipid Disorders and Management in Diabetes

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  1. Lipid Disorders and Management in Diabetes Om P. Ganda MD Joslin Diabetes Center Harvard Medical school Boston, MA Web-conference, April 8, 2010

  2. MRFIT: Cholesterol and CVD Mortality in Men With Type 2 Diabetes Age-Adjusted CVD deaths per10,000 person-years 280 Plasma cholesterol (mg/dL) Stamler et al. Diabetes Care. 1993;16:434-444.

  3. Smaller VLDL IDL LPL LPL Large LDL Low TG pool High LDLR Larger VLDL LPL LPL/HL Remnants Small LDL Smaller LDL HL TG Smaller HDL CETP HDL Pathophysiology of Dyslipidemia in Type 2 Diabetes Krauss RM. Diabetes Care. 2004;27:1496-1504.

  4. Rate ratio & 95% CI STATINbetter PLACEBO better 0.4 0.6 0.8 1.0 1.2 1.4 HPS: Major Vascular Events by LDL-C and Prior Diabetes 24% SE 3 reduction (2P<.00001) The Heart Protection Study Collaborative Group. Lancet. 2003;361:2005-2016.

  5. CARDS: Treatment Effect onthe Primary End Points by Subgroup * units in mmol/L (mg/dL) ** N (% of randomised) .2 .4 .6 .8 1 1.2 Favors Atorvastatin Favors Placebo Colhoun HM, et al. Lancet 2004;364:685-696

  6. Major Vascular Events with or without Diabetes:Effect per 1mM/L reduction in LDL-cholesterol 14 RCTs 18686 with DM 71370 without DM No differences by Presence or absence of vascular disease, Other risk-factors, or baseline lipid levels CTT Collaborators Lancet 2008, 371: 117-125 Total mortality RR 0-88 (0.84-0.91)

  7. Meta-analysis of Intensive Statin Trials:Coronary Death or Myocardial Infarction DM : Similar outcome Cannon,CP et al JACC 2006; 48: 438-445

  8. ARR : 0.77 vs 1.36 %/yr

  9. Statins and Primary End Points Risk of Primary Event (%) Kastelein et al. Eur Heart J. 2005;7(suppl F):F27-F33.

  10. TG <150 mg/dL Associated With Lower Risk of CHD Events Independent of LDL-C Level PROVE IT-TIMI 22 Trial N = 4162 Referent HR: 0.85 P=.180 CHD Eventa Rate After 30 Daysc, % HR: 0.84 P=.192 HR: 0.72 P=.017 LDL-C ≥70 LDL-C <70 TG <150 TG ≥150 Death, MI, and recurrent ACS ACS patients on atorvastatin 80 mg or pravastatin 40 mg Adjusted for age, gender, low HDL-C, smoking, hypertension, obesity, diabetes, prior statin therapy, prior ACS, peripheral vascular disease, and treatment Miller M, et al. J ACC. 2008;51:724-730.

  11. TNT: major CVD Events in Patients with LDL < 70 mg/dl Barter,P et al NEJM 2007; 357: 1301-1310

  12. Lifestyle changes and secondary causes Pharmacologic therapy Fibrate Niacin Omega-3 Fatty acids Combination therapy Management of Dyslipidemia beyond LDL

  13. ACCORD- Lipid Results The ACCORD Study Group. N Engl J Med 2010;10.1056/NEJMoa1001282

  14. ACCORD Lipid: Primary Outcome in Prespecified Subgroups The ACCORD Study Group. N Engl J Med 2010;10.1056/NEJMoa1001282

  15. ADA Lipid Goals and Recommendations 2009 • Lifestyle modifications • Primary LDL –C goal < 100 mg/dl ; If CVD:LDL-C < 70 mg/dl is an option • Statin therapy added to lifestyle changes, regardless of baseline LDL , if • Overt CVD; • Without CVD but age > 40 yr + one or more other CVD risk factors • Without overt CVD and age < 40 yr -Consider statin if LDL-C > 100 mg/dl or multiple risk factors , despite lifestyle therapy. • In drug treated patients, a reduction in LDL-C of ~30-40% from baseline , if LDL targets not achieved with maximum tolerated statin therapy. • Triglycerides < 150 mg/dl; HDL-C > 40 mg/dl (men),> 50 mg/dl (women): Desirable • Combination therapy to achieve lipid goals may be needed but outcome studies pending. Diabetes Care 2009; 32(suppl1): S13-S61

  16. ADA and ACC Consensus Statement on Lipoprotein Management *Smoking, HBP, f/h premature CHD Brunzell JD et al. Diabetes Care. 2008;31:811-822.

  17. Algorithm for Apo-B Testing in Patients with Dyslipidemia Order Lipid profile LDL-C > 100mg/dl TG >500 mg/dl Lifestyle + Statin Rx Goal: LDL-C < 100 mg/dl Treat TG to < 500 mg/dl Fibrates and/or Fish oil if > 1000 mg/dl CVD-No CVD-yes Statin Rx if LDL > 100 Intensify Statin Rx LDL< 100, TG > 200* LDL< 70, TG > 200* Measure Apo-B Apo-B >80mg/dl ApoB< 90mg/dl Intensify LDL Rx or add Fibrate/Niacin Continue current Rx; may need Fibrate/ Niacin * 150 if fasting Ganda, OP Endocrine Practice 2009; 15: 370-376

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