Developmental programming and diabetes - The human experience and insight from animal models

Abstract

Children born to mothers, rather than to fathers, with type 1 diabetes (type 1 DM) or type 2 diabetes (type 2 DM) may have a greater susceptibility to diabetes and obesity in later life, inferring a role for in utero or early post-natal influences on the developing child. This review summarises the studies contributing to this hypothesis, noting some of the controversies including the potential for residual confounding and the influence of maternal BMI. Animal models demonstrate that maternal hyperglycaemia leads to persistent disorders of offspring pancreatic β cell secretory capacity, abnormal insulin signaling in insulin-sensitive tissues and abnormal development of the hypothalamus, associated with aberrant control of energy regulation and obesity in adult life. Prospective studies, particularly follow-up of children born to diabetic mothers participating in RCTs of improved glycemic control are needed to accurately assess the transgenerational influences of maternal diabetes and to evaluate mechanisms inferred from animal data.