Diabetic Dyslipidemia
- Approximately 80% of deaths in diabetic patients are attributable to cardiovascular disease (CVD), which in turn is highly correlated with diabetic dyslipidemia.1
- Among diabetics, Asian Indians have higher risk of heart attacks than whites, but blacks have only half the risk, which in turn is attributed to more favorable dyslipidemia.2
- Diabetic dyslipidemia is a significant predictor of CVD events and mortality and consists of elevated levels of triglyceride, low HDL-C (high-density lipoprotein cholesterol), and an increased proportion of small dense LDL.
- CVD risk is reduced to a greater extent by lowering the LDL-C and blood pressure than lowering blood sugar. Although management of LDL-C (low-density lipoprotein cholesterol), HDL-C, non-HDL cholesterol, and triglyceride are important, only HMG-CoA reductase inhibitors (statins) has indisputable proven efficacy.3
- Statins have demonstrated 27-40% reductions in LDL-C in all placebo-controlled trials and subsequent decreases in occurrence of cardiovascular events and mortality of the same magnitude in persons with and without diabetes.4, 5 This benefit extends to those without high LDL-C levels.3, 6
- There is ambiguity concerning the role of fibrates and nicotinic acid in CVD risk reduction despite significant improvement in the lipid profile.7-9
- Since the evidence in favor of lowering LDL is so overwhelming, the primary emphasis of lipid management in people with diabetes tends to focus on LDL-C.6 Statin therapy in addition to dietary modification is recommended as first-line management guidelines for lipid control in diagnosed diabetes patients with and without confirmed CVD.(see Medications Statins)
- The two major insulin sensitizing agents ─pioglitazone and rosiglitazone─ have significantly different effects on diabetic dyslipidemia despite similar effects on blood sugar levels. Pioglitazone compared with rosiglitazone is associated with significant improvements in triglycerides, HDL cholesterol, LDL particle concentration, and LDL particle size.10
- Controlled clinical trials with pioglitazone 45 mg/d has shown a decrease of 52 mg/dl for triglycerides compared to 13 mg/dl increase with rosiglitazone 8 mg/d. The respective changes by these agents were an increase in HDL of 5 mg/dl vs 2 mg dl, an increase in LDL of 12 mg/dl vs 23 mg/dl. LDL particle concentration was reduced with pioglitazone and increased with rosiglitazone. LDL particle size increased more with pioglitazone.10
Sources
1. O’Keefe JH, Miles J, Harris W, Moe R, McCallister B. Improving the adverse cardiovascular prognosis of Type 2 diabetes. Mayo Clinic proceedings. 1999;74:171-180.
2. UKPDS 32. Ethnicity and cardiovascular disease. The incidence of myocardial infarction in white, South Asian, and Afro-Caribbean patients with type 2 diabetes (U.K. Prospective Diabetes Study 32). Diabetes Care. 1998;21(8):1271-1277.
3. Enas E.A., Hancy Chennikkara Pazhoor MD, Arun Kuruvila MBBS, Krishnaswami Vijayaraghavan MD F. Intensive Statin Therapy for Indians:Part I Benefits. Indian heart journal. 2010;(In press).
4. Collins R, Armitage J, Parish S, Sleigh P, Peto R. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. Jun 14 2003;361(9374):2005-2016.
5. Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. Aug 21 2004;364(9435):685-696.
6. Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. Oct 8 2005;366(9493):1267-1278.
7. Keech A, Simes RJ, Barter P, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. Nov 26 2005;366(9500):1849-1861.
8. Ginsberg HN, Elam MB, Lovato LC, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. Apr 29 2010;362(17):1563-1574.
9. Canner PL, Berge KG, Wenger NK, et al. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986;8(6):1245-1255.
10. Goldberg RB, Kendall DM, Deeg MA, et al. A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care. Jul 2005;28(7):1547-1554.