LDL SUBCLASS PHENOTYPES AND THE INSULIN-RESISTANCE SYNDROME IN WOMEN

Background. Low-density lipoprotein (LDL) subclass phenotype B, charac terized by predominance of small, dense LDL particles, is associated w ith elevated plasma triglycerides and apolipoprotein B and with lower high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I. Bec ause these abnormalities resemble the dyslipidemia of insulin resistan ce, we examined associations of LDL subclass phenotype with plasma ins ulin levels and with other aspects of the insulin resistance syndrome. Methods and Results. LDL subclass phenotypes were determined by gradi ent gel electrophoresis in 682 female twins aged 30 to 91 years who pa rticipated in the second examination of the Kaiser Permanente Women Tw ins Study. Prevalence of phenotype B and the intermediate phenotype (I ) increased strongly with age, obesity, and non-insulin-dependent diab etes. In multivariate analysis of nondiabetic women, phenotype B or I was independently associated with each aspect of the insulin resistanc e syndrome, including higher plasma triglycerides, waist-hip ratio, fa sting and postload insulin levels, and systolic blood pressure and low er HDL cholesterol levels after adjustment for age and body mass index . The prevalence of phenotype B or I rose progressively from 5.6% in w omen with no manifestations of the insulin resistance syndrome to 100% in women with four syndrome components. In 25 nondiabetic, monozygoti c twin pairs discordant for subclass phenotype, the twins with phenoty pe 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 e xplaining their associations with LDL subclass phenotype. Conclusions. Small, dense LDL is an integral feature of the insulin resistance syn drome. Nongenetic (ie, behavioral or environmental) factors are import ant for the expression of the phenotype and for its association with o ther heart disease risk factors.