Influence of maternal obesity on insulin sensitivity and secretion in offspring

OBJECTIVE—The purpose of this study was to clarify the effects of maternal obesity on insulin sensitivity and secretion in offspring.RESEARCH DESIGN AND METHODS—Fifty-one offspring of both sexes of obese (Ob group) and 15 offspring of normal-weight (control group) mothers were studied. Plasma glucose, insulin, and C-peptide were measured during an oral glucose tolerance test (OGTT). Insulin sensitivity was calculated using the oral glucose insulin sensitivity index, and insulin secretion and β-cell glucose sensitivity were computed by a mathematical model. Fasting leptin and adiponectin were also measured. Body composition was assessed by dual-X-ray absorptiometry.RESULTS—No birth weight statistical difference was observed in the two groups. Of the Ob group, 69% were obese and 19% were overweight. The Ob group were more insulin resistant than the control group (398.58 ± 79.32 vs. 513.81 ± 70.70 ml^?1 · min^?1 · m^?2 in women, P < 0.0001; 416.42 ± 76.17 vs. 484.242 ± 45.76 ml^?1 · min^?1 · m^?2 in men, P < 0.05). Insulin secretion after OGTT was higher in Ob group than in control group men (63.94 ± 21.20 vs. 35.71 ± 10.02 nmol · m^?2, P < 0.01) but did not differ significantly in women. β-Cell glucose sensitivity was not statistically different between groups. A multivariate analysis of variance showed that maternal obesity and offspring sex concurred together with BMI and β-cell glucose sensitivity to determine the differences in insulin sensitivity and secretion observed in offspring.CONCLUSIONS—Obese mothers can give birth to normal birth weight babies who later develop obesity and insulin resistance. The maternal genetic/epigenetic transmission shows a clear sexual dimorphism, with male offspring having a higher value of insulin sensitivity (although not statistically significant) associated with significantly higher insulin secretion than female offspring.Type 2 diabetes is spreading out among young people as the incidence of obesity is increasing over time. This evidence has induced the American Diabetes Association (1) to include into the new classification recommendations of diabetes a form of type 2 diabetes with pubertal onset, variable insulin secretion, and decreased insulin sensitivity, strongly associated with obesity, which includes 10–20% of all diabetes in childhood and youth.Scientists have provided a pathophysiological explanation of this phenomenon by suggesting that the development of type 2 diabetes in youth reflects the combination of insulin resistance and relative insulin deficiency. However, the limited β-cell capacity is regarded as being of “little significance” (2) in the absence of obesity.Familial aggregation of BMI is well established in the medical literature. In a Swedish study on monozygotic twins reared in different familial contexts, within-pair correlations for BMI were 70% for men and 66% for women; these figures were quite similar for twins reared together, suggesting that familial environment did not play a relevant role in BMI in identical twins (3). Similar values for correlation coefficients (75%) were also found in a U.S. population of monozygotic twins (4).However, epigenetics also seems to contribute, together with genetic predisposition, to the development of obesity. Studies of inheritance unequivocally show that BMI of children correlates more closely with maternal than with paternal BMI, suggesting that in addition to the genetic influences, the in utero environment may contribute to the development of obesity in offspring. In fact, overweight/obese women are more likely to give birth to heavier babies (>90th centile) than normal-weight mothers (5). Studies of inheritance clearly demonstrated a stricter correlation between a child''s BMI and maternal rather than paternal BMI, suggesting that the in utero environment may contribute to the development of obesity in offspring (6,7). Gillman et al. (8) found that maternal BMI was an influencing variable in association with gestational diabetes and offspring obesity. Furthermore, Khan et al. (9–11) demonstrated that the consumption of a diet rich in saturated fat starting before conception and continuing through weaning led to increased hyperinsulinemia, adiposity, hypertension, and endothelial dysfunction in offspring at 6 months of age. Very recently, Shankar et al. (5) demonstrated that, at least in rats, maternal overweight at conception contributes to offspring obesity and insulin resistance and that programming of obesity occurs in the absence of changes in birth weights.However, at least to our best knowledge, there is only one study (12) in the literature that investigated insulin sensitivity but not insulin secretion in young lean offspring of obese parents compared with offspring of normal-weight parents. This study (12) failed to demonstrate any significant difference between groups.Our center follows obese subjects almost exclusively, and morbidly obese individuals represent >50% of the outpatient population. Recently, we have started to systematically study insulin sensitivity and insulin secretion in the offspring of obese and morbidly obese patients, after the observation that some of the young individuals with at least one parent, usually the mother, affected by obesity had impaired glucose tolerance (IGT) and/or hypertension independent of their body weight. In the present investigation insulin sensitivity, insulin secretion, and body composition were studied in offspring with a different maternal phenotype, namely normal weight or obesity.