Birth weight and the metabolic syndrome: thrifty phenotype or thrifty genotype?

Inverse correlations have been reported between birth weight and the Metabolic Syndrome (abdominal obesity, insulin resistance, hyperinsulinemia, glucose intolerance, dyslipidemia, and hypertension). These correlations are thought to reflect primarily nutritional inadequacies during fetal and early life. We explored familial influences on these correlations.

Using birth weight data on 602 subjects from 65 pedigrees, we partitioned phenotypic correlations into familial and non-familial. The former are usually regarded as reflecting primarily genetic influences, although they may also reflect environmental influences that are shared by family members, and the latter reflect random environmental influences.

A consistent pattern of positive familial and inverse non-familial correlations were observed. The strongest familial correlations were between birth weight and fasting insulin (r = 0.58, p = 0.002), leptin (r = 0.48, p = 0.021), split proinsulin (r=0.51, p = 0.090), and heart rate (r = 0.39, p = 0.037). An inverse familial correlation was observed with HDL cholesterol (r = -0.28, p = 0.018). Non-familial correlations were weaker and only two-- subscapular-to-triceps skinfold ratio and fasting insulin--were statistically significant.

Since the familial and non-familial correlations were in opposite directions, we attribute the former to the pleiotropic effects of genes. Specifically, we conclude that genes that increase birth weight also worsen the Metabolic Syndrome in adult life. Since the inverse correlations reported in the literature reflect mainly cohorts born in the early part of the 20th century, improved maternal nutrition since then may have allowed the expression of genetic influences in our participants, all of whom were born after 1950.