Arteriosclerosis, Vol 10, 223-231, Copyright © 1990 by American Heart Association

ARTICLES

Insulin resistance is associated with lipid and lipoprotein abnormalities in subjects with varying degrees of glucose tolerance

M Laakso, H Sarlund and L Mykkanen
Department of Medicine, Kuopio University Central Hospital, Finland.

We tested the hypothesis that insulin resistance, rather than high insulin level, is associated with lipid and lipoprotein changes favoring atherosclerosis independently of the glucose tolerance status. To this aim, 50 subjects with normal glucose tolerance, 28 subjects with impaired glucose tolerance, and 54 subjects with noninsulin- dependent diabetes (NIDDM) were studied. Subjects with low glucose disposal rate (GDR) or a high degree of insulin resistance as measured by the euglycemic hyperinsulinemic clamp technique had lower high density lipoprotein (HDL) cholesterol and higher total and very low density lipoprotein (VLDL) triglycerides than did subjects with high GDR (highest GDR tertile). These associations were independent of fasting insulin level and other confounding factors. In stepwise multiple linear regression analysis, GDR was the most important single variable associated with HDL cholesterol and VLDL triglyceride level independently of age, obesity, distribution of obesity (waist/hip ratio), 2-hour glucose level, and free fatty acid concentration. We conclude: 1) insulin resistance measured by the euglycemic clamp technique is associated with adverse lipid and lipoprotein changes favoring atherosclerosis not only in nondiabetic subjects (as shown in previous studies) but also in impaired glucose tolerance and NIDDM subjects; 2) the association of high insulin level with adverse lipid and lipoprotein changes indirectly reflects the association of insulin resistance with lipid and lipoprotein levels; and 3) HDL cholesterol and VLDL triglycerides are independently associated with insulin- mediated glucose uptake, which may indicate that these lipoproteins have separate sites of interaction with insulin action.

This article has been cited by other articles:

				D. Vaidya, M. Szklo, K. Liu, P. J. Schreiner, A. G. Bertoni, and P. Ouyang Defining the Metabolic Syndrome Construct: Multi-Ethnic Study of Atherosclerosis (MESA) cross-sectional analysis Diabetes Care, August 1, 2007; 30(8): 2086 - 2090. [Abstract] [Full Text] [PDF]

				the Metascreen Writing Committee The Metabolic Syndrome Is a Risk Indicator of Microvascular and Macrovascular Complications in Diabetes: Results from Metascreen, a multicenter diabetes clinic-based survey Diabetes Care, December 1, 2006; 29(12): 2701 - 2707. [Abstract] [Full Text] [PDF]

				D. Estrada-Smith, A. R. Collins, X. Wang, C. Crockett, L. Castellani, A. J. Lusis, and R. C. Davis Impact of Chromosome 2 Obesity Loci on Cardiovascular Complications of Insulin Resistance in LDL Receptor-Deficient C57BL/6 Mice. Diabetes, August 1, 2006; 55(8): 2265 - 2271. [Abstract] [Full Text] [PDF]

				R. Kahn, J. Buse, E. Ferrannini, and M. Stern The Metabolic Syndrome: Time for a Critical Appraisal: Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes Diabetes Care, September 1, 2005; 28(9): 2289 - 2304. [Abstract] [Full Text] [PDF]

				J. Pihlajamaki, H. Gylling, T. A. Miettinen, and M. Laakso Insulin resistance is associated with increased cholesterol synthesis and decreased cholesterol absorption in normoglycemic men J. Lipid Res., March 1, 2004; 45(3): 507 - 512. [Abstract] [Full Text] [PDF]

				T. Bagis, A. Gokcel, H. B. Zeyneloglu, E. Tarim, E. B. Kilicdag, and B. Haydardedeoglu The Effects of Short-Term Medroxyprogesterone Acetate and Micronized Progesterone on Glucose Metabolism and Lipid Profiles in Patients with Polycystic Ovary Syndrome: A Prospective Randomized Study J. Clin. Endocrinol. Metab., October 1, 2002; 87(10): 4536 - 4540. [Abstract] [Full Text] [PDF]

				S. H. Golden, A. R. Folsom, J. Coresh, A. R. Sharrett, M. Szklo, and F. Brancati Risk Factor Groupings Related to Insulin Resistance and Their Synergistic Effects on Subclinical Atherosclerosis: The Atherosclerosis Risk in Communities Study Diabetes, October 1, 2002; 51(10): 3069 - 3076. [Abstract] [Full Text] [PDF]

				A. Kareinen, L. Viitanen, P. Halonen, S. Lehto, and M. Laakso Cardiovascular Risk Factors Associated With Insulin Resistance Cluster in Families With Early-Onset Coronary Heart Disease Arterioscler. Thromb. Vasc. Biol., August 1, 2001; 21(8): 1346 - 1352. [Abstract] [Full Text] [PDF]

				M. E. Silfen, A. M. Manibo, D. J. McMahon, L. S. Levine, A. R. Murphy, and S. E. Oberfield Comparison of Simple Measures of Insulin Sensitivity in Young Girls with Premature Adrenarche: The Fasting Glucose to Insulin Ratio May Be a Simple and Useful Measure J. Clin. Endocrinol. Metab., June 1, 2001; 86(6): 2863 - 2868. [Abstract] [Full Text] [PDF]

				B. L. Wajchenberg Subcutaneous and Visceral Adipose Tissue: Their Relation to the Metabolic Syndrome Endocr. Rev., December 1, 2000; 21(6): 697 - 738. [Abstract] [Full Text]

				L. Ibáñez, C. Valls, N. Potau, M. V. Marcos, and F. de Zegher Sensitization to Insulin in Adolescent Girls to Normalize Hirsutism, Hyperandrogenism, Oligomenorrhea, Dyslipidemia, and Hyperinsulinism after Precocious Pubarche J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3526 - 3530. [Abstract] [Full Text]

				G. Gennarelli, J. Holte, L. Berglund, C. Berne, M. Massobrio, and H. Lithell Prediction models for insulin resistance in the polycystic ovary syndrome Hum. Reprod., October 1, 2000; 15(10): 2098 - 2102. [Abstract] [Full Text] [PDF]

				J. Pihlajamaki, L. Karjalainen, P. Karhapaa, I. Vauhkonen, M.-R. Taskinen, S. S. Deeb, and M. Laakso G-250A Substitution in Promoter of Hepatic Lipase Gene Is Associated With Dyslipidemia and Insulin Resistance in Healthy Control Subjects and in Members of Families With Familial Combined Hyperlipidemia Arterioscler. Thromb. Vasc. Biol., July 1, 2000; 20(7): 1789 - 1795. [Abstract] [Full Text] [PDF]

				J. Pihlajamaki, L. Karjalainen, P. Karhapaa, I. Vauhkonen, and M. Laakso Impaired Free Fatty Acid Suppression During Hyperinsulinemia Is a Characteristic Finding in Familial Combined Hyperlipidemia, but Insulin Resistance Is Observed Only in Hypertriglyceridemic Patients Arterioscler. Thromb. Vasc. Biol., January 1, 2000; 20(1): 164 - 170. [Abstract] [Full Text] [PDF]

				S. C. Riemens, A. Van Tol, B. K. Stulp, and R. P. F. Dullaart Influence of insulin sensitivity and the TaqIB cholesteryl ester transfer protein gene polymorphism on plasma lecithin:cholesterol acyltransferase and lipid transfer protein activities and their response to hyperinsulinemia in non-diabetic men J. Lipid Res., August 1, 1999; 40(8): 1467 - 1474. [Abstract] [Full Text]

				P. W. F. Wilson, W. B. Kannel, H. Silbershatz, and R. B. D'Agostino Clustering of Metabolic Factors and Coronary Heart Disease Arch Intern Med, May 24, 1999; 159(10): 1104 - 1109. [Abstract] [Full Text] [PDF]

				L. Karjalainen, J. Pihlajamaki, P. Karhapaa, and M. Laakso Impaired Insulin-Stimulated Glucose Oxidation and Free Fatty Acid Suppression in Patients with Familial Combined Hyperlipidemia : A Precursor Defect for Dyslipidemia? Arterioscler. Thromb. Vasc. Biol., October 1, 1998; 18(10): 1548 - 1553. [Abstract] [Full Text] [PDF]

				D. L. Rainwater, B. D. Mitchell, M. C. Mahaney, and S. M. Haffner Genetic Relationship Between Measures of HDL Phenotypes and Insulin Concentrations Arterioscler. Thromb. Vasc. Biol., December 1, 1997; 17(12): 3414 - 3419. [Abstract] [Full Text]

				L. Mykkanen, S. M. Haffner, D. L. Rainwater, P. Karhapaa, H. Miettinen, and M. Laakso Relationship of LDL Size to Insulin Sensitivity in Normoglycemic Men Arterioscler. Thromb. Vasc. Biol., July 1, 1997; 17(7): 1447 - 1453. [Abstract] [Full Text]

				J. Pihlajamaki, J. Rissanen, S. Heikkinen, L. Karjalainen, and M. Laakso Codon 54 Polymorphism of the Human Intestinal Fatty Acid Binding Protein 2 Gene Is Associated With Dyslipidemias But Not With Insulin Resistance in Patients With Familial Combined Hyperlipidemia Arterioscler. Thromb. Vasc. Biol., June 1, 1997; 17(6): 1039 - 1044. [Abstract] [Full Text]

				J. Jeppesen, H. O. Hein, P. Suadicani, and F. Gyntelberg 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., June 1, 1997; 17(6): 1114 - 1120. [Abstract] [Full Text]

				M. Laakso, L. Karjalainen, and P. Lempiainen-Kuosa Effects of Losartan on Insulin Sensitivity in Hypertensive Subjects Hypertension, September 1, 1996; 28(3): 392 - 396. [Abstract] [Full Text]

				G. Barba, F. P. Cappuccio, L. Russo, F. Stinga, R. Iacone, and P. Strazzullo Renal Function and Blood Pressure Response to Dietary Salt Restriction in Normotensive Men Hypertension, May 1, 1996; 27(5): 1160 - 1164. [Abstract] [Full Text]

				S. Agewall, B. Fagerberg, S. Attvall, I. Wendelhag, V. Urbanavicius, and J. Wikstrand Carotid Artery Wall Intima-Media Thickness Is Associated With Insulin-Mediated Glucose Disposal in Men at High and Low Coronary Risk Stroke, June 1, 1995; 26(6): 956 - 960. [Abstract] [Full Text]