Circulation, Vol 88, 381-387, Copyright © 1993 by American Heart Association
JV Selby, MA Austin, B Newman, D Zhang, CP Quesenberry Jr, EJ Mayer and RM Krauss
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.
ARTICLES
LDL subclass phenotypes and the insulin resistance syndrome in women
Division of Research, Kaiser Permanente Medical Care Program, Oakland, Calif. 94611.
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