Metabolic Defects in Prediabetic Kuwaiti Arabs and Indians

What this study is testing ClinicalTrials.gov NCT04268862 ↗

Description as written by the study sponsor.

Insulin resistance and beta cell dysfunction are the major core defects responsible for the development of type 2 diabetes (T2DM). Although insulin resistance is the early metabolic defect detected in subjects destined to develop T2DM, it is the beta cell failure which is responsible for the development of hyperglycemia. Longitudinal and cross-sectional studies have demonstrated that, initially, the compensatory hyperinsulinemia is sufficient to offset the insulin resistance and maintain normal glucose tolerance. However, when the beta cell fails to adequately compensate for the insulin resistance, glucose homeostasis deteriorates. Initially, this is manifest as impaired glucose tolerance (IGT) and later as overt diabetes. It follows that the level of beta cell failure at which hyperglycemia becomes evident depends upon the prevailing level of insulin resistance. A more severe insulin resistance results in development of overt hyperglycemia at lower level of beta cell failure. The investigators previously have shown that the severity of insulin resistance varies amongst different ethnic groups (Arabs versus Indians). Thus, the level of beta cell failure at which overt hyperglycemia becomes evident amongst each ethnic group also varies. Thus, individuals/ethnic groups with more severe insulin resistance, overt hyperglycemia becomes evident at lower level of beta cell dysfunction. Conversely, severe beta cell dysfunction is required for evert hyperglycemia to develop in individuals/ethnicities with less severe insulin resistance. In the present study, the investigators aim to quantitate beta cell function with the gold standard technique (i.e. hyperglycemic clamp) in Arab and Indian non-diabetic individuals and relate the level of beta cell function to the prevailing level of insulin resistance measured as the glucose infusion rate divided by the mean plasma insulin concentration during the clamp.