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Insulin resistance appears to be the best predictor of the development of diabetes in the children of patients with type 2 diabetes, but the mechanism responsible is unknown.

We performed hyperinsulinemic–euglycemic clamp studies in combination with infusions of [6,6-²H₂]glucose in healthy, young, lean, insulin-resistant offspring of patients with type 2 diabetes and insulin-sensitive control subjects matched for age, height, weight, and physical activity to assess the sensitivity of liver and muscle to insulin. Proton (¹H) magnetic resonance spectroscopy studies were performed to measure intramyocellular lipid and intrahepatic triglyceride content. Rates of whole-body and subcutaneous fat lipolysis were assessed by measuring the rates of [²H₅]glycerol turnover in combination with microdialysis measurements of glycerol release from subcutaneous fat. We performed ³¹P magnetic resonance …