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Effects of Physical Activity and Weight Loss on Skeletal Muscle Mitochondria and Relationship to Glucose Control in Type 2 Diabetes Mellitus

¹Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania

Correspondence: Kelley{at}dom.pitt.edu

Key Words: exercise • weight loss • insulin resistance • obesity • diabetes • mitochondria

Background:Reduced mitochondrial capacity in skeletal muscle occurs in type-2 diabetes and in those at increased risk for this disorder, but the extent to which mitochondrial dysfunction in type-2 DM is remediable by physical activity and weight loss intervention is uncertain.

Objective:To address whether an intervention of daily moderate-intensity exercise combined with moderate weight loss can increase skeletal muscle mitochondrial content in type-2 DM and address the relationship to amelioration of insulin resistance and hyperglycemia.

Methods:Muscle biopsies were obtained before and after a 4-month intervention to assess mitochondrial morphology, mtDNA content, and mitochondrial enzyme activities. Glucose control, body composition, aerobic fitness, and insulin sensitivity were measured.

Results:In response to a weight loss of 7.1±0.8% and a 12±1.6% improvement in VO₂max (p<0.05), insulin sensitivity improved by 59±21% (p<0.05). There were significant increases in skeletal muscle mitochondrial density (by 67±17%; p<0.01), cardiolipin content (55±17%; P<0.01) and mitochondrial oxidation enzymes. Energy expenditure during physical activity correlated with the degree of improvement in insulin sensitivity (r=0.84, P<0.01), and in turn, improvement in mitochondrial content was a strong correlate of intervention-induced improvement in HbA1c and fasting plasma glucose.

Conclusion:Intensive short-term lifestyle modifications can restore mitochondrial content and functional capacity in skeletal muscle in type-2 DM. The improvement in the oxidative capacity of skeletal muscle may be a key component mediating salutary effects of lifestyle interventions upon hyperglycemia and insulin resistance.

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