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. 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 [6,6-2H 2]glucose and [l-13C]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 μmol · 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%) in comparison with healthy matched individuals (17 ± 1%; P = 0.04) and correlated with the degree of the impairment of insulin-stimulated glucose metabolism (R2 = 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.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Internal Medicine