Endocrine Abstracts

An estimated 100 million people worldwide currently suffer from type 2 diabetes mellitus (T2DM). The incidence of T2DM is steadily escalating throughout the world in people from a wide range of ethnic groups and all social and economic levels. Parallel with the global epidemic of T2DM in adults, an 'emerging epidemic' of T2DM has been observed in youth over the last decade. Research and clinical experience in adults have established that insulin resistance is a major risk factor for developing T2DM. However, insulin resistance alone is not sufficient to cause diabetes, which will develop only if insulin secretion by beta-cells is inadequate. Glucose homeostasis depends on the balance between insulin action in insulin-sensitive tissues and insulin secretion by the pancreatic beta-cells. This balance is a hyperbolic relationship between insulin sensitivity and secretion (insulin sensitivity X secretion = Disposition Index). The disposition index (DI) seems to be a heritable characteristic. When insulin sensitivity decreases insulin secretion must increase to compensate for insulin resistance and maintain the DI. A lower DI in the face of insulin resistance reflects the inability of the beta-cells to upregulate insulin secretion. Failure to upregulate insulin secretion in the presence of insulin resistance causes the full blown expression of diabetes.

Our experience in youth with T2DM suggests that the early abnormality is insulin resistance compounded later with beta-cell failure. The basis for this proposition is the recognition that all the clinical characteristics of youth with T2DM share a common feature which is insulin resistance. The clinical characteristics of youth with T2DM are obesity, high-risk family history of T2DM, age of onset at mid-puberty, high-risk minority ethnicity, female gender and 'syndrome X'. In this lecture data will be presented on how these features impact insulin sensitivity and secretion in childhood ultimately leading to T2DM.