title: Insulin resistance of protein anabolism accompanies that of glucose metabolism in lean, glucose-tolerant offspring of persons with type 2 diabetes.
abstract: OBJECTIVE
  To test whether protein anabolic resistance is an early defect in type 2 diabetes (T2D).
  
  
  METHODS
  Seven lean, normoglycemic T2D offspring (T2D-O) and eight matched participants without family history (controls; C) underwent a 3-hour hyperinsulinemic (40 mU/m2/min), euglycemic (5.5 mmol/L) and isoaminoacidemic clamp. Whole-body glucose and protein kinetics were measured with d-[3-3H]glucose and l-[l-13C]leucine, respectively. Plasma amino acids were measured by liquid chromatography-tandem mass spectrometry.
  
  
  RESULTS
  Fasting glycemia and glucose kinetic variables did not differ between groups. Clamp decreases in glucose rate of appearance were not different, but rate of disappearance increased 29% less in T2D-O, to a significantly lower rate. Fasting leucine was higher in T2D-O, but kinetics did not differ. Clamp increases in leucine oxidation and decreases in endogenous rate of appearance (protein breakdown) were equal, but in T2D-O, non-oxidative rate of disappearance (protein synthesis) did not increase and net balance (synthesis-breakdown) did not become positive as in C.
  
  
  CONCLUSIONS
  Resistance of whole-body protein anabolism (synthesis and net balance) accompanies resistance of glucose uptake in T2D-O. Mechanisms responsible, possible roles in the increased risk of developing diabetes, and its potential impact on long-term protein balance require definition.
authors.affiliation: Crabtree Nutrition Laboratories, Division of Endocrinology and Metabolism, Department of Medicine, McGill University Health Centre Research Institute, Montreal, Quebec, Canada; Department of Animal Science, Faculty of Agricultural and Environmental Sciences, McGill University, Montreal, Sainte-Anne-de-Bellevue, Quebec, Canada.
authors.forename: Sergio A
authors.initials: SA
authors.lastname: Burgos
authors.affiliation: Division of Endocrinology , Memorial University of Newfoundland , St. John's, Newfoundland and Labrador , Canada.
authors.forename: Vikram
authors.initials: V
authors.lastname: Chandurkar
authors.affiliation: Crabtree Nutrition Laboratories, Division of Endocrinology and Metabolism, Department of Medicine , McGill University Health Centre Research Institute , Montreal, Quebec , Canada.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Tsoukas
authors.affiliation: Crabtree Nutrition Laboratories, Division of Endocrinology and Metabolism, Department of Medicine , McGill University Health Centre Research Institute , Montreal, Quebec , Canada.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Chevalier
authors.affiliation: Crabtree Nutrition Laboratories, Division of Endocrinology and Metabolism, Department of Medicine , McGill University Health Centre Research Institute , Montreal, Quebec , Canada.
authors.forename: José A
authors.initials: JA
authors.lastname: Morais
authors.affiliation: Crabtree Nutrition Laboratories, Division of Endocrinology and Metabolism, Department of Medicine , McGill University Health Centre Research Institute , Montreal, Quebec , Canada.
authors.forename: Marie
authors.initials: M
authors.lastname: Lamarche
authors.affiliation: Crabtree Nutrition Laboratories, Division of Endocrinology and Metabolism, Department of Medicine , McGill University Health Centre Research Institute , Montreal, Quebec , Canada.
authors.forename: Errol B
authors.initials: EB
authors.lastname: Marliss
keywords: Glucose Metabolism; Insulin Resistance In Vivo; Offspring; Protein Metabolism