LDL subclass phenotypes and the insulin resistance syndrome in women

BACKGROUND Low-density lipoprotein (LDL) subclass phenotype B, characterized by predominance of small, dense LDL particles, is associated with elevated plasma triglycerides and apolipoprotein B and with lower high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I. Because these abnormalities resemble the dyslipidemia of insulin resistance, we examined associations of LDL subclass phenotype with plasma insulin levels and with other aspects of the insulin resistance syndrome. METHODS AND RESULTS LDL subclass phenotypes were determined by gradient gel electrophoresis in 682 female twins aged 30 to 91 years who participated in the second examination of the Kaiser Permanente Women Twins Study. Prevalence of phenotype B and the intermediate phenotype (I) increased strongly with age, obesity, and non-insulin-dependent diabetes. In multivariate analysis of nondiabetic women, phenotype B or I was independently associated with each aspect of the insulin resistance syndrome, including higher plasma triglycerides, waist-hip ratio, fasting and postload insulin levels, and systolic blood pressure and lower HDL cholesterol levels after adjustment for age and body mass index. The prevalence of phenotype B or I rose progressively from 5.6% in women with no manifestations of the insulin resistance syndrome to 100% in women with four syndrome components. In 25 nondiabetic, monozygotic twin pairs discordant for subclass phenotype, the twins with phenotype B (or I) had significantly higher levels of body mass index, waist-hip ratio, and systolic blood pressure than their twins with phenotype A. Thus, nongenetic variation in these risk factors is important in explaining their associations with LDL subclass phenotype. CONCLUSIONS Small, dense LDL is an integral feature of the insulin resistance syndrome. Nongenetic (ie, behavioral or environmental) factors are important for the expression of the phenotype and for its association with other heart disease risk factors.