Epigenetics and life-long consequences of an adverse nutritional and diabetic intrauterine environment

The phenomenon that adverse environmental exposures in early life are associated with increased susceptibilities for many adult, particularly metabolic diseases, is now referred to as ‘developmental origins of health and disease (DOHAD)’ or ‘Barker’ hypothesis. Fetal overnutrition and undernutrition have similar long-lasting effects on the setting of the neuroendocrine control systems, energy homeostasis, and metabolism, leading to life-long increased morbidity. There are sensitive time windows during early development, where environmental cues can program persistent epigenetic modifications which are generally assumed to mediate these gene–environment interactions. Most of our current knowledge on fetal programing comes from animal models and epidemiological studies in humans, in particular the Dutch famine birth cohort. In industrialized countries, there is more concern about adverse long-term consequences of fetal overnutrition, i.e. by exposure to gestational diabetes mellitus and/or maternal obesity which affect 10–20% of pregnancies. Epigenetic changes due to maternal diabetes/obesity may predispose the offspring to develop metabolic disease later in life and, thus, transmit the adverse environmental exposure to the next generation. This vicious cycle could contribute significantly to the worldwide metabolic disease epidemics. In this review article, we focus on the epigenetics of an adverse intrauterine environment, in particular gestational diabetes, and its implications for the prevention of complex disease.

Testing the fetal overnutrition hypothesis; the relationship of maternal and paternal adiposity to adiposity, insulin resistance and cardiovascular risk factors in Indian children

ObjectiveWe aimed to test the fetal overnutrition hypothesis by comparing the associations of maternal and paternal adiposity (sum of skinfolds) with adiposity and cardiovascular risk factors in children.DesignChildren from a prospective birth cohort had anthropometry, fat percentage (bio-impedance), plasma glucose, insulin and lipid concentrations and blood pressure measured at 9·5 years of age. Detailed anthropometric measurements were recorded for mothers (at 30 ± 2 weeks’ gestation) and fathers (5 years following the index pregnancy).SettingHoldsworth Memorial Hospital, Mysore, India.SubjectsChildren (n504), born to mothers with normal glucose tolerance during pregnancy.ResultsTwenty-eight per cent of mothers and 38 % of fathers were overweight/obese (BMI ≥ 25·0 kg/m2), but only 4 % of the children were overweight/obese (WHO age- and sex-specific BMI ≥ 18·2 kg/m2). The children's adiposity (BMI, sum of skinfolds, fat percentage and waist circumference), fasting insulin concentration and insulin resistance increased with increasing maternal and paternal sum of skinfolds adjusted for the child's sex, age and socio-economic status. Maternal and paternal effects were similar. The associations with fasting insulin and insulin resistance were attenuated after adjusting for the child's current adiposity.ConclusionsIn this population, both maternal and paternal adiposity equally predict adiposity and insulin resistance in the children. This suggests that shared family environment and lifestyle, or genetic/epigenetic factors, influence child adiposity. Our findings do not support the hypothesis that there is an intra-uterine overnutrition effect of maternal adiposity in non-diabetic pregnancies, although we cannot rule out such an effect in cases of extreme maternal obesity, which is rare in our population.