(Circulation. 1995;92:1770-1778.)
© 1995 American Heart Association, Inc.
Articles |
Prospective Study of Small LDLs as a Risk Factor for Non–Insulin Dependent Diabetes Mellitus in Elderly Men and Women
From the Department of Epidemiology, School of Public Health and Community Medicine, University of Washington, Seattle (M.A.A., K.L.E., C.N.); the Department of Medicine, University of Kuopio, Finland (L.M., J.K., K.P., M.L.); and the Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center at San Antonio (S.M.H.).
Correspondence to Melissa A. Austin, PhD, Department of Epidemiology, Box 358770, School of Public Health and Community Medicine, University of Washington, Seattle, WA 98195. E-mail maustin@u.washington.edu.
Background The excess risk of atherosclerosis among patients with non–insulin dependent diabetes mellitus (NIDDM) is well documented. However, the presence of conventional risk factors cannot fully account for this excess risk, and the underlying mechanism remains to be elucidated. The present study prospectively evaluated the role of small LDL, a known risk factor for coronary heart disease, as a risk factor for the development of NIDDM.
Methods and Results The study was based on a nested case-control sample of 204 elderly men and women from Kuopio, Finland. LDL subclasses were characterized by size with 2% to 14% polyacrylamide gels produced by recently developed methods. Logistic regression analysis showed that subjects with a predominance of small LDL (LDL subclass phenotype B) had a greater than twofold increased risk for developing NIDDM over the 3.5-year follow-up period. This association was independent of age, sex, glucose intolerance, and body mass index but was not independent of fasting triglyceride or insulin levels. Further, an increase of 5Å in LDL diameter was associated with a 16% decrease in risk of NIDDM, and a composite variable of LDL diameter and triglyceride and HDL cholesterol concentrations, identified by principal-components analysis, was also associated with NIDDM. These associations may be attributable to the role of small LDL as a marker for insulin resistance.
Conclusions This study is the first to demonstrate that a predominance of small LDL particles is a risk factor for the future development of NIDDM, and it implies that small LDL contributes to risk of coronary heart disease in prediabetics.
Key Words: lipoproteins • diabetes mellitus • aging • risk factors
This article has been cited by other articles:
 |
|
 |
|
  M. Mayr Metabolomics: Ready for the Prime Time? Circ Cardiovasc Genet, October 1, 2008; 1(1): 58 - 65. [Full Text] [PDF]
|
|
|
|
 |
|
 I. Aeberli, M. B Zimmermann, L. Molinari, R. Lehmann, D. l'Allemand, G. A Spinas, and K. Berneis Fructose intake is a predictor of LDL particle size in overweight schoolchildren Am. J. Clinical Nutrition, October 1, 2007; 86(4): 1174 - 1178. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Yu, S. J Murdoch, S. J Parikh, S. M Marcovina, A. Cobitz, H. Chen, and J. D Brunzell Rosiglitazone increases LDL particle size and buoyancy and decreases C-reactive protein in patients with type 2 diabetes on statin therapy Diabetes and Vascular Disease Research, December 1, 2006; 3(3): 189 - 196. [Abstract] [PDF]
|
|
|
|
 |
|
 A. S. Wierzbicki Diabetic dyslipidaemia: the triad Eur. Heart J. Suppl., October 1, 2006; 8(suppl_F): F30 - F33. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Festa, K. Williams, A. J.G. Hanley, J. D. Otvos, D. C. Goff, L. E. Wagenknecht, and S. M. Haffner Nuclear Magnetic Resonance Lipoprotein Abnormalities in Prediabetic Subjects in the Insulin Resistance Atherosclerosis Study Circulation, June 28, 2005; 111(25): 3465 - 3472. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. D. Badzioch, R. P. Igo Jr, F. Gagnon, J. D. Brunzell, R. M. Krauss, A. G. Motulsky, E. M. Wijsman, and G. P. Jarvik Low-Density Lipoprotein Particle Size Loci in Familial Combined Hyperlipidemia: Evidence for Multiple Loci From a Genome Scan Arterioscler Thromb Vasc Biol, October 1, 2004; 24(10): 1942 - 1950. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Todorova, A. Kubaszek, J. Pihlajamaki, J. Lindstrom, J. Eriksson, T. T. Valle, H. Hamalainen, P. Ilanne-Parikka, S. Keinanen-Kiukaanniemi, J. Tuomilehto, et al. The G-250A Promoter Polymorphism of the Hepatic Lipase Gene Predicts the Conversion from Impaired Glucose Tolerance to Type 2 Diabetes Mellitus: The Finnish Diabetes Prevention Study J. Clin. Endocrinol. Metab., May 1, 2004; 89(5): 2019 - 2023. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Austin, K. L. Edwards, M. J. McNeely, W. L. Chandler, D. L. Leonetti, P. J. Talmud, S. E. Humphries, and W. Y. Fujimoto Heritability of Multivariate Factors of the Metabolic Syndrome in Nondiabetic Japanese Americans Diabetes, April 1, 2004; 53(4): 1166 - 1169. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Austin, K. L. Edwards, S. A. Monks, K. M. Koprowicz, J. D. Brunzell, A. G. Motulsky, M. C. Mahaney, and J. E. Hixson Genome-wide scan for quantitative trait loci influencing LDL size and plasma triglyceride in familial hypertriglyceridemia J. Lipid Res., November 1, 2003; 44(11): 2161 - 2168. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Winkler, T. Konrad, S. Fullert, I. Friedrich, R. Destani, M. W. Baumstark, K. Krebs, H. Wieland, and W. Marz Pioglitazone Reduces Atherogenic Dense LDL Particles in Nondiabetic Patients With Arterial Hypertension: A double-blind, placebo-controlled study Diabetes Care, September 1, 2003; 26(9): 2588 - 2594. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Valabhji and R. S Elkeles Dyslipidaemia in type 2 diabetes: epidemiology and biochemistry The British Journal of Diabetes & Vascular Disease, May 1, 2003; 3(3): 184 - 189. [Abstract] [PDF]
|
|
|
|
|
|
K. K. Berneis and R. M. Krauss Metabolic origins and clinical significance of LDL heterogeneity J. Lipid Res., September 1, 2002; 43(9): 1363 - 1379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.F. Ebenbichler, M. Laimer, S. Kaser, A. Ritsch, A. Sandhofer, H. Weiss, F. Aigner, and J.R. Patsch Relationship Between Cholesteryl Ester Transfer Protein and Atherogenic Lipoprotein Profile in Morbidly Obese Women Arterioscler Thromb Vasc Biol, September 1, 2002; 22(9): 1465 - 1469. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kazumi, A. Kawaguchi, K. Sakai, T. Hirano, and G. Yoshino Young Men With High-Normal Blood Pressure Have Lower Serum Adiponectin, Smaller LDL Size, and Higher Elevated Heart Rate Than Those With Optimal Blood Pressure Diabetes Care, June 1, 2002; 25(6): 971 - 976. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. Lindblad, R. D. Langer, D. L. Wingard, R. G. Thomas, and E. L. Barrett-Connor Metabolic Syndrome and Ischemic Heart Disease in Elderly Men and Women Am. J. Epidemiol., March 1, 2001; 153(5): 481 - 489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. von Eckardstein, H. Schulte, and G. Assmann Risk for Diabetes Mellitus in Middle-Aged Caucasian Male Participants of the PROCAM Study: Implications for the Definition of Impaired Fasting Glucose by the American Diabetes Association J. Clin. Endocrinol. Metab., September 1, 2000; 85(9): 3101 - 3108. [Abstract] [Full Text]
|
|
|
|
|
|
B. V. Howard, D. C. Robbins, M. L. Sievers, E. T. Lee, D. Rhoades, R. B. Devereux, L. D. Cowan, R. S. Gray, T. K. Welty, O. T. Go, et al. LDL Cholesterol as a Strong Predictor of Coronary Heart Disease in Diabetic Individuals With Insulin Resistance and Low LDL : The Strong Heart Study Arterioscler Thromb Vasc Biol, March 1, 2000; 20(3): 830 - 835. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Mykkanen, J. Kuusisto, S. M. Haffner, M. Laakso, and M. A. Austin LDL Size and Risk of Coronary Heart Disease in Elderly Men and Women Arterioscler Thromb Vasc Biol, November 1, 1999; 19(11): 2742 - 2748. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. L. Edwards, M. C. Mahaney, A. G. Motulsky, and M. A. Austin Pleiotropic Genetic Effects on LDL Size, Plasma Triglyceride, and HDL Cholesterol in Families Arterioscler Thromb Vasc Biol, October 1, 1999; 19(10): 2456 - 2464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Sartipy, G. Camejo, L. Svensson, and E. Hurt-Camejo Phospholipase A2 Modification of Low Density Lipoproteins Forms Small High Density Particles with Increased Affinity for Proteoglycans and Glycosaminoglycans J. Biol. Chem., September 3, 1999; 274(36): 25913 - 25920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Haffner, R. D'Agostino Jr, D. Goff, B. Howard, A. Festa, M. F. Saad, and L. Mykkanen LDL Size in African Americans, Hispanics, and Non-Hispanic Whites : The Insulin Resistance Atherosclerosis Study Arterioscler Thromb Vasc Biol, September 1, 1999; 19(9): 2234 - 2240. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. G. Scheffer, S. J. L. Bakker, R. J. Heine, and T. Teerlink Measurement of LDL particle size in whole plasma and serum by high performance gel-filtration chromatography using a fluorescent lipid probe Clin. Chem., October 1, 1998; 44(10): 2148 - 2151. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Donahue, J. A. Bean, R. D. Donahue, R. B. Goldberg, and R. J. Prineas Does Insulin Resistance Unite the Separate Components of the Insulin Resistance Syndrome? : Evidence From the Miami Community Health Study Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2413 - 2417. [Abstract] [Full Text]
|
|
|
|
|
|
P. G. Scheffer, S. J. L. Bakker, R. J. Heine, and T. Teerlink Measurement of low-density lipoprotein particle size by high-performance gel-filtration chromatography Clin. Chem., October 1, 1997; 43(10): 1904 - 1912. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sattar, I. A. Greer, J. Louden, G. Lindsay, M. McConnell, J. Shepherd, and C. J. Packard Lipoprotein Subfraction Changes in Normal Pregnancy: Threshold Effect of Plasma Triglyceride on Appearance of Small, Dense Low Density Lipoprotein J. Clin. Endocrinol. Metab., August 1, 1997; 82(8): 2483 - 2491. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
H. R. Superko Beyond LDL Cholesterol Reduction Circulation, November 15, 1996; 94(10): 2351 - 2354. [Full Text]
|
|
|
|
|
|
W. H. Capell, A. Zambon, M. A. Austin, J. D. Brunzell, and J. E. Hokanson Compositional Differences of LDL Particles in Normal Subjects With LDL Subclass Phenotype A and LDL Subclass Phenotype B Arterioscler Thromb Vasc Biol, August 1, 1996; 16(8): 1040 - 1046. [Abstract] [Full Text]
|
|