Genetic and Metabolic Markers for the Development of Diabetes after Gestational Diabetes Mellitus

University dissertation from Department of Clinical Sciences, Lund University

Abstract: The aims of this work were to determine the prevalence of postpartum diabetes among women with gestational diabetes mellitus (GDM) in a prospective study 5 years postpartum; to characterize these women according to insulin secretion, insulin sensitivity, autoimmunity and genetics; and to identify possible markers and predictors for the development of manifest diabetes. The subjects were recruited through a regional screening programme in which oral glucose tolerance tests (OGTTs) are routinely offered to all pregnant women. The prevalence of MODY mutations among women with GDM and a family history of diabetes was found to be 5%. Arabian women were more insulin resistant than Scandinavian women with the same BMI, and showed impaired beta cell compensation for their degree of insulin resistance. GDM might share some genetic features with type 1 diabetes in Scandinavian women. The prevalence of manifest diabetes 5 years after GDM was 30% in our population. Antenatal levels of fasting glucose and HbA1c were identified as biochemical predictors of diabetes following GDM. These are easy to measure, and are relatively cheap, and could help identify women at particularly high risk of developing diabetes postpartum. Counselling regarding future risk of diabetes could then be initiated during pregnancy in high-risk individuals. The rs8050136 variant in the FTO (fat mass and obesity associated) gene was associated with an increased risk of developing postpartum diabetes, probably due to its effect on increasing obesity . Thus, genetic testing may provide a means of identifying pregnant women at high risk of developing postpartum diabetes.