Obesity and diabetes in pregnancy: a vicious circle?

Intrauterine exposure to diabetes during pregnancy – either because the mother already has diabetes or because gestational diabetes is triggered by the pregnancy – increases the risk that the baby will develop weight gain and insulin-resistant (known as type 2) diabetes later in life. Because these babies are themselves likely to be at increased risk of gestational diabetes, the population risk for type 2 diabetes could accelerate in just a few generations. The problem is compounded by maternal obesity and there is evidence from some high-risk populations that only modest increases in maternal obesity may be enough to precipitate gestational diabetes.

High BMI

Recent research in the Department of Paediatrics and Medical Research Council (MRC) Epidemiology Unit led by Professor David Dunger and Dr Ken Ong has shown that high maternal body mass index (BMI) increases the risk of obesity in offspring. In collaboration with colleagues in Uppsala, Sweden, the group is looking at variations in maternal glucose and lipid metabolism during pregnancy using state-of-the-art cold-isotope techniques. These complex physiological studies are being carried out at the Wellcome Trust Clinical Research Facility on the Cambridge Biomedical Campus at Addenbrooke’s Hospital.

The findings show that maternal obesity and insulin resistance are determinants of fetal and newborn body fat, even where glucose levels are normal. Furthermore, although maternal glucose levels in late pregnancy are an important determinant of body fat at birth, over the first two years of life this relationship tends to decline and, by the age of two years, the pre-pregnancy BMI of the mother is the more important determinant of offspring weight.

Feeding on demand

Maternal weight gain and genes predisposing to type 2 diabetes may not be the only factors determining gestational diabetes risk in mothers. Professor Dunger and Dr Clive Petry, with support from an MRC project grant, have also found evidence that fetal genotypes associated with increased fetal growth may modify the metabolism of the mother. It seems likely that these effects are a result of the fetus trying to boost its own growth by increasing nutritional demand through the secretion of placental hormones into the maternal circulation. The important inference here is that if some fetal genotypes influence the risk of maternal gestational diabetes then, in combination with increased rates of maternal obesity, this could contribute to the current worldwide epidemic of diabetes.

Baby growth

The group has also identified rapid postnatal weight gain as a major risk factor for adult obesity and risk of type 2 diabetes. To explore this further, the investigators are using the Cambridge Baby Growth Study of over 1000 infants, originally established with European Union funding by Professor Ieuan Hughes in the Department of Paediatrics and now funded by the MRC. The group is looking at the effects of feeding regimes, including breast, bottle and early introduction of solids and cows’ milk, as well as measures of satiety, to determine hormonal markers of differential weight and height gain.

The aim over the next five years is to arrive at a full evaluation of these complex prenatal and postnatal determinants of obesity risk in childhood and type 2 diabetes risk in later life. The accurate prediction of risk might lead to the development of new intervention strategies that will reduce the vicious circle of maternal obesity and diabetes risk in future generations.

For more information, please contact the authors Professor David Dunger (dbd25@cam.ac.uk) and Dr Ken Ong (ken.ong@mrc-epid.cam.ac.uk) at the Department of Paediatrics. Dr Ong is also at the MRC Epidemiology Unit, Institute of Metabolic Science.