Grant: Operating Grant

Rising obesity rates, sedentary lifestyles and an aging population continue to drive increases in the prevalence of the most common form of diabetes, type 2 (T2D). It is predicted that 1 in 3 Canadians will have diabetes or pre-diabetes by the year 2020. Importantly, the occurrence of another form of diabetes, Gestational Diabetes Mellitus (GDM) is also increasing. GDM currently afflicts 3-14% of pregnant women and is a condition in which women transiently develop glucose intolerance during pregnancy, most frequently beginning in the late second or early third trimester when there is significant insulin resistance. Importantly, women with GDM have a very high rate of progression to T2D (25-50% within 5 years, up to 70% within 10 years). Strong evidence is also emerging that fetal exposure to medical conditions associated with GDM puts the child at a significantly increased risk of obesity and T2D later in life. Ultimately, it is the inability of the insulin-producing beta cells to respond to changing metabolic demands that leads to the development of both GDM and T2D. The ultimate failure of insulin producing cells is not well understood and is controversial. In this proposal we will identify factors in the blood that may be responsible for the beta cell failure observed in GDM and T2D, as well as the progression from GDM to T2D. This will be accomplished using a sophisticated blood screening method called mass spectroscopy. Using this method we will examine if these circulating factors are differentially expressed in diabetes and pre-diabetes compared to normal glucose tolerant control subjects. Then using animal models we will determine the factors we discover are causally important in the development of GDM and T2D. We will further determine if these factors can lead to the development of novel early detection screening methods. Such screens may allow very early detection of GDM or T2D and facilitate prevention or the onset of this disease.