Objective To test whether protein anabolic resistance is an early defect in type 2 diabetes (T2D).
Research design and 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.
- Insulin Resistance In Vivo
- Protein Metabolism
- Glucose Metabolism
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Contributors SAB, VC, MAT, SC, and EBM designed the experimental protocol. SAB, VC, MAT, SC, JAM, ML, and EBM recruited and screened participants and conducted the clamp experiment. SAB, SC, ML, and EBM performed and/or supervised the laboratory analyses and analyzed data. SAB, SC, and EBM wrote the manuscript. All authors approved the manuscript.
Funding This work was supported by a grant from Canadian Institutes of Health Research to EBM (MOP-62889).
Competing interests None declared.
Ethics approval Ethics Review Board of the McGill University Health Centre.
Provenance and peer review Not commissioned; externally peer reviewed.
Data sharing statement No additional data are available.
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