Advertisement

Is There a Simple Way to Identify Insulin-Resistant Individuals at Increased Risk of Cardiovascular Disease?

      The goal of this study was to evaluate the ability of various routine measures of lipoprotein metabolism to identify patients who were insulin resistant and dyslipidemic, and therefore, at increased risk of cardiovascular disease. For this purpose, insulin resistance was quantified by determining the steady-state plasma glucose concentration during the insulin suppression test in 449 apparently healthy patients. The low-density lipoprotein (LDL) particle diameter and subclass phenotype were measured by gradient gel electrophoresis in 1,135 patients. Pearson’s correlation coefficients and receiver-operating characteristic curves were used to evaluate measures of lipoprotein metabolism as potential markers of insulin resistance and LDL phenotype. The results indicated that the ratio of the plasma concentrations of triglyceride to high-density lipoprotein cholesterol was the best predictor of insulin resistance and LDL particle diameter. The optimal triglyceride/high-density lipoprotein cholesterol ratio for predicting insulin resistance and LDL phenotype was 3.5 mg/dl; a value that identified insulin-resistant patients with a sensitivity and specificity comparable to the criteria currently proposed to diagnose the metabolic syndrome. The sensitivity and specificity were even greater for identification of patients with small, dense, LDL particles. In conlusion, a plasma triglyceride/high-density lipoprotein cholesterol concentration ratio ≥3.5 provides a simple means of identifying insulin-resistant, dyslipidemic patients who are likely to be at increased risk of cardiovascular disease.
      To read this article in full you will need to make a payment

      References

        • Miller G.J.
        • Miller N.E.
        Plasma high-density-lipoprotein concentration and development of ischaemic heart disease.
        Lancet. 1975; 1: 16-19
        • Carlson L.A.
        • Bottiger L.E.
        • Ahfeldt P.E.
        Risk factors for myocardial infarction in the Stockholm prospective study.
        Acta Med Scand. 1979; 206: 351-360
        • Castelli W.P.
        • Garrison R.J.
        • Wilson P.W.F.
        • Abbott R.O.
        • Kalonsdian S.
        • Kannel W.B.
        Incidence of coronary heart disease and lipoprotein cholesterol levels.
        JAMA. 1986; 256: 2385-2387
        • Hokanson J.E.
        • Austin M.A.
        Plasma triglyceride level in a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level.
        J Cardiovasc Risk. 1996; 3: 213-219
        • Austin M.A.
        • Breslow J.L.
        • Hennekens C.H.
        • Buring J.E.
        • Willett W.S.
        • Krauss R.M.
        Low-density lipoprotein subclass patterns and risk of myocardial infarction.
        JAMA. 1988; 260: 1917-1921
        • Reaven G.M.
        • Chen Y.D.-I.
        • Jeppesen J.
        • Maheux P.
        • Krauss R.M.
        Insulin resistance and hyperinsulinemia in individuals with small, dense, low density lipoprotein particles.
        J Clin Invest. 1993; 92: 141-146
        • Jeppesen J.
        • Hein H.O.
        • Suadicani P.
        • Gyntelberg F.
        Relation of high TG-low HDL cholesterol and LDL cholesterol to the incidence of ischemic heart disease. An 8-year follow-up in the Copenhagen Male Study.
        Arterioscler Thromb Vasc Biol. 1997; : 1114-1120
        • Gaziano J.M.
        • Hennekens C.H.
        • O’Donnell C.J.
        • Breslow J.L.
        • Buring J.E.
        Fasting triglycerides, high-density lipoprotein, and risk of myocardial infarction.
        Circulation. 1997; 96: 2520-2525
        • Pei D.
        • Jones C.N.O.
        • Bhargava R.
        • Chen Y.-D.I.
        • Reaven G.M.
        Evaluation of octreotide to assess insulin-mediated glucose disposal by the insulin suppression test.
        Diabetologia. 1994; 37: 843-845
        • Shen S.-W.
        • Reaven G.M.
        • Farquhar J.W.
        Comparison of impedance to insulin-mediated glucose uptake in normal and diabetic subjects.
        J Clin Invest. 1970; 49: 2151-2160
        • Greenfield M.S.
        • Doberne L.
        • Kraemer F.B.
        • Tobey T.A.
        • Reaven G.M.
        Assessment of insulin resistance with the insulin suppression test and the euglycemic clamp.
        Diabetes. 1981; 30: 387-392
        • Yeni-Komshian H.
        • Carantoni M.
        • Abbasi F.
        • Reaven G.M.
        Relationship between several surrogate estimates of insulin resistance and quantification of insulin-mediated glucose disposal in 490 healthy, nondiabetic volunteers.
        Diabetes Care. 2000; 23: 171-175
        • Hales C.N.
        • Randle P.J.
        Immunoassay of insulin with insulin-antibody precipitate.
        Biochem J. 1963; 88: 137-146
        • Cheal K.L.
        • Abbasi F.
        • Lamendola C.
        • McLaughlin T.
        • Reaven G.M.
        • Ford E.S.
        Relationship to insulin resistance of the Adult Treatment Panel III diagnostic criteria for identification of the metabolic syndrome.
        Diabetes. 2004; 53: 1195-1200
        • Olefsky J.M.
        • Farquhar J.W.
        • Reaven G.M.
        Reappraisal of the role of insulin in hypertriglyceridemia.
        Am J Med. 1974; 57: 551-560
        • Laws A.
        • Reaven G.M.
        Evidence for an independent relationship between insulin resistance and fasting plasma HDL-cholesterol, triglyceride and insulin concentrations.
        J Int Med. 1992; 231: 25-30
        • Krauss R.M.
        • Dreon D.M.
        Low-density-lipoprotein subclasses and response to a low-fat diet in healthy men.
        Am J Clin Nutr. 1995; 62: 478S-487S
        • Dreon D.M.
        • Fernstrom H.A.
        • Williams P.T.
        • Krauss R.M.
        Reduced LDL particle size in children consuming a very-low-fat diet is related to parental LDL-subclass patterns.
        Am J Clin Nutr. 2000; 71: 1611-1616
        • Dreon D.M.
        • Fernstrom H.A.
        • Williams P.T.
        • Krauss R.M.
        LDL subclass patterns and lipoprotein response to a low-fat, high-carbohydrate diet in women.
        Arterioscler Thromb Vasc Biol. 1997; 17: 707-714
        • Woodward M.
        Epidemiology Study Design and Data Analysis. Chapman & Hall/CRC Press, Boca Raton, Florida1999
        • NCEP Expert Panel
        Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III).
        JAMA. 2002; 285: 2846-2897
        • Laakso M.
        How good a marker is insulin level for insulin resistance?.
        Am J Epidemiol. 1992; 137: 959-965
        • Reaven G.M.
        Role of insulin resistance in human disease.
        Diabetes. 1988; 37: 1595-1607
        • Reaven G.M.
        The insulin resistance syndrome.
        Curr Atheroscler Rep. 2003; 5: 364-371
        • Dobiasova M.
        • Frohlich J.
        The plasma parameter log (TG/HDL-C) as an atherogenic index.
        Clin Biochem. 2001; 34: 583-588
        • Yip J.
        • Facchini F.S.
        • Reaven G.M.
        Resistance to insulin-mediated glucose disposal as a predictor of cardiovascular disease.
        J Clin Endocrinol Metab. 1998; 83: 2773-2776
        • Facchini F.S.
        • Hua N.
        • Abbasi F.
        • Reaven G.M.
        Insulin resistance as a predictor of age-related diseases.
        J Clin Endocrinol Metab. 2001; 86: 3574-3578