Prospective Study of Small LDLs as a Risk Factor for Non–Insulin Dependent Diabetes Mellitus in Elderly Men and Women

Abstract

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.