Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes.
Level 4 - case-series / case-control
Matched cross-sectional/case-control physiological study
PubMed 14960743 · doi:10.1056/NEJMoa031314
What was done
Hyperinsulinemic-euglycemic clamp studies combined with [6,6-2H2]glucose infusions were conducted in healthy, young, lean, insulin-resistant offspring of patients with type 2 diabetes and insulin-sensitive controls matched for age, height, weight, and physical activity. Proton (1H) magnetic resonance spectroscopy (MRS) was performed to measure intramyocellular lipid and intrahepatic triglyceride content. Whole-body and subcutaneous fat lipolysis rates were measured via [2H5]glycerol turnover and subcutaneous microdialysis. 31P MRS was used to assess skeletal muscle mitochondrial oxidative-phosphorylation activity.
What was found
Compared to matched insulin-sensitive controls, insulin-resistant offspring showed: - An approximately 60% lower rate of insulin-stimulated muscle glucose uptake (P<0.001) - An increase of approximately 80% in intramyocellular lipid content (P=0.005) - A reduction of approximately 30% in muscle mitochondrial phosphorylation activity (P=0.01) - No significant differences in systemic or localized lipolysis rates, or in plasma concentrations of tumor necrosis factor-alpha, interleukin-6, resistin, or adiponectin.
Why it matters
This study provides evidence that skeletal muscle mitochondrial dysfunction and intramyocellular lipid accumulation are present in young, lean individuals at high risk for type 2 diabetes prior to the onset of obesity or overt diabetes, pointing toward an early metabolic defect.
Limits
The abstract does not report the total sample size (n). The observational case-control design can identify physiological differences and associations but cannot establish direct causality. Long-term progression to clinical diabetes was not measured.
Cited by
- contradicts Mitochondria in type 2 diabetics function at half the rate of mitochondria in people without type 2 diabetes.