Insulin and 2-Hour Glucose Levels Are Inversely Related to Lp(a) Concentrations Controlled for LPA Genotype

From the Department of Genetics, Southwest Foundation for Biomedical Research (D.L.R.), and the Division of Clinical Epidemiology, Department of Medicine, University of Texas Health Science Center (S.M.H.), San Antonio, Tex.

Correspondence to David L. Rainwater, PhD, Department of Genetics, PO Box 760549, Southwest Foundation for Biomedical Research, San Antonio, TX 78245-0549. E-mail david{at}darwin.sfbr.org

Abstract—In this study we assessed the relationship of lipoprotein(a) [Lp(a)] with diabetes status and with measures of glucose and insulin in a population of Mexican Americans having a high prevalence of non–insulin-dependent diabetes mellitus (NIDDM). Because of enormous allelic diversity at LPA [the locus encoding the apo(a) protein] that directly influences Lp(a) concentrations, it was first necessary to adjust for the large effects of variation at LPA. We calculated residual Lp(a) concentration as the difference between observed and expected; expected Lp(a) concentration was based on information from all family members sharing each identical-by-descent (IBD) allele. We found significant effects of sex and age on residual Lp(a) concentrations that increased with age (P=0.0004) and in females (P=0.0034). Although diabetes status per se was not related to residual Lp(a) concentrations (P=0.097), we found that residual Lp(a) concentrations were inversely correlated with fasting insulin (P=0.0017) and with insulin (P=0.0028) and glucose (P=0.0429) concentrations measured 2 hours after a glucose challenge. Furthermore, significant inverse correlations with the 2 insulin measures were observed for a subgroup of nondiabetic individuals. Inclusion of 2 lipid measures (plasma concentrations of cholesterol and triglycerides) in the models showed that the correlations with insulin and glucose were independent of the relationship between Lp(a) concentrations and the lipid measures. Also, we determined the residual size for each apo(a) isoform by adjusting for the IBD isoform group average. Although not related to diabetes status, residual apo(a) isoform size was positively correlated with fasting insulin (P=0.0013) and with 2-hour glucose (P=0.0246) and 2-hour insulin (P=0.0182) concentrations. In addition, significant correlations for all 4 measures were found for the subgroup of nondiabetic individuals. Thus, the results demonstrate that glucose-intolerant individuals have significantly lower residual Lp(a) concentrations and a significant increase of residual apo(a) size.

Key Words: non–insulin-dependent diabetes mellitus • glucose tolerance • Lp(a) • apo(a) genotypes • Mexican Americans

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