ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Diabetologia. 2020 Feb;63(2):324–337. PMID:31773193

Maternal obesity is a risk factor for the development of type 2 diabetes in the offspring. Exposure to maternal obesity alters pancreatic islet structure and function, including reduced beta-cell mass and impaired glucose stimulated insulin secretion, which both increase susceptibility to type 2 diabetes. However, most previous studies have not assessed if these changes in pancreatic islet structure and function are explained by other confounding factors, such as offspring obesity, offspring high fat diets or ageing.

This mouse study was undertaken to understand the potential sex-specific changes in islet function in offspring born to obese dams, and whether these are independent of offspring obesity, glucose intolerance and ageing. Female C57BL/6J mice were fed ad libitum either chow or obesogenic diet prior to and throughout pregnancy and lactation. The offspring were weaned onto a chow diet and remained on this diet until the end of the study. They found sex differences in type 2 diabetes susceptibility in offspring as a consequence of exposure to maternal obesity and this could potentially be driven by differences in islet function. Islets from female mice that were exposed to maternal obesity showed increased insulin secretion as well as improved mitochondrial function. In addition, these islets had increased expression of the estrogen receptor and a reduction in the markers of apoptosis. In contrast islets from exposed male mice had compromised mitochondrial function, with reduced expression of key calcium channel proteins that are required for insulin secretion, and defects in beta-cell insulin granules. In male mice, islet function became compromised later in life following the onset of obesity and insulin resistance.

Understanding the maternal factors (such as for example hyperinsulinaemia, hyperglycaemia and hyperlipidaemia) and critical developmental periods that might underlie the programming of metabolic adversity and islet function across the life course of the offspring is an important research goal.