Postabsorptive and insulin-stimulated energy homeostasis and leucine turnover in offspring of type 2 diabetic patients

OBJECTIVE- This study was performed to ascertain whether insulin resistance with respect to protein metabolism is an additional primary metabolic abnormality affecting insulin-resistant offspring of type 2 diabetic parents, along with insulin resistance with respect to glucose and lipid metabolism. RESEARCH DESIGN AND METHODS- We studied 18 young, nonobese offspring of type 2 diabetic parents and 27 healthy matched (by means of dual-energy X-ray absorption) individuals with the bolus plus continuous infusion of [6,6-H-2(2)] glucose and [1-C-13] leucine in combination with the insulin clamp (40 mU (.) m(-2) (.) min(-1)). RESULTS- Fasting plasma leucine, phenylalanine, alanine, and glutamine concentrations, as well as the glucose and leucine turnover (reciprocal pool model: 155 +/- 10 vs. 165 +/- 5 mumol (.) kg lean body mass(-1) (.) h(-1) in offspring of type 2 diabetic patients and healthy matched individuals, respectively), were also not different. During the clamp, glucose turnover rates were significantly reduced in offspring of type 2 diabetic patients (7.1 +/- 0.5) in comparison with healthy matched individuals (9.9 +/- 0.6 mg (.) kg lean body mass(-1) (.) min(-1); P < 0.01). Also, the suppression of leucine turnover was impaired in offspring of type 2 diabetic patients (12 +/- 1%) suppression in comparison with healthy matched individuals (17 1%; P = 0.04) and correlated with the degree of the impairment of insulin-stimulated glucose metabolism (R-2 = 0.13; P = 0.02). CONCLUSIONS- Nonobese, nondiabetic, insulin-resistant offspring of type 2 diabetic patients were characterized by an impairment of insulin-dependent suppression of protein breakdown, which was proportional to the impairment of glucose metabolism. These results demonstrate that in humans, a primary in vivo impairment of insulin action affects glucose and fatty acid metabolism as previously shown and also protein/amino acid metabolism.