Early metabolic defects in Arab subjects with strong family history of Type 2 diabetes

Aims and objective: It is widely accepted that the genetic make-up of the subject plays a pivotal role in the development of insulin resistance and β cell failure. The objective of this study was to examine whether the same or distinct genetic backgrounds contribute to the development of insulin resistance and β cell failure. Methods: We examined insulin sensitivity and β cell function in lean normal glucose tolerance subjects from 3 multigeneration Arab families. Families 1 and 2 had strong history of Type 2 diabetes (T2DM), while no member of family 3 had T2DM. Results: Subjects in family 1 manifested increased basal plasma free fatty acid (FFA) concentration and impaired suppression of plasma FFA during the OGTT compared to subjects in family 3. Subjects in family 2 had comparable fasting plasma FFA and suppression of plasma FFA during the OGTT to family 3. Both the absolute plasma glucose concentrations, and incremental area under the plasma glucose curve (ΔG_0-120) during the OGTT were comparable in subjects of families 1 and 2, and were decreased in subjects of family 3. Whole body and muscle insulin sensitivity were comparable in subjects from families 2 and 3, and both were significantly decreased in subjects of family 1. Beta cell function was comparable in subjects of families 1 and 3 and was significantly decreased in subjects of family 2. Conclusion: These results demonstrate that distinct genetic background contributes to the development of insulin resistance and β cell dysfunction in Arab individuals.