Adipokines and their relation to maternal energy substrate production, insulin resistance and fetal size

The role of adipokines in the regulation of energy substrate production in non-diabetic pregnant women has not been elucidated. We hypothesize that serum concentrations of adiponectin are related to fetal growth via maternal fat mass, insulin resistance and glucose production, and further, that serum levels of leptin are associated with lipolysis and that this also influences fetal growth. Hence, we investigated the relationship between adipokines, energy substrate production, insulin resistance, body composition and fetal weight in non-diabetic pregnant women in late gestation.

Twenty pregnant women with normal glucose tolerance were investigated at 36 weeks of gestation at Uppsala University Hospital. Levels of adipokines were related to rates of glucose production and lipolysis, maternal body composition, insulin resistance, resting energy expenditure and estimated fetal weights. Rates of glucose production and lipolysis were estimated by stable isotope dilution technique.

Median (range) rate of glucose production was 805 (653-1337) μmol/min and that of glycerol production, reflecting lipolysis, was 214 (110-576) μmol/min. HOMA insulin resistance averaged 1.5 ± 0.75 and estimated fetal weights ranged between 2670 and 4175 g (-0.2 to 2.7 SDS). Mean concentration of adiponectin was 7.2 ± 2.5mg/L and median level of leptin was 47.1 (9.9-58.0) μg/L. Adiponectin concentrations (7.2 ± 2.5mg/L) correlated inversely with maternal fat mass, insulin resistance, glucose production and fetal weight, r=-0.50, p<0.035, r=-0.77, p<0.001, r=-0.67, p<0.002, and r=-0.51, p<0.032, respectively. Leptin concentrations correlated with maternal fat mass and insulin resistance, r=0.76, p<0.001 and r=0.73, p<0.001, respectively. There was no correlation between maternal levels of leptin and rate of glucose production or fetal weight. Neither were any correlations found between levels of leptin or adiponectin and maternal lipolysis or resting energy expenditure.

The inverse correlations between levels of maternal adiponectin and insulin resistance as well as endogenous glucose production rates indicate that low levels of adiponectin in obese pregnant women may represent one mechanism behind increased fetal size. Maternal levels of leptin are linked to maternal fat mass and its metabolic consequences, but the data indicate that leptin lacks a regulatory role with regard to maternal lipolysis in late pregnancy.