Effects of physical activity and weight loss on skeletal muscle mitochondria and relationship with glucose control in type 2 diabetes.
OBJECTIVE
Reduced mitochondrial capacity in skeletal muscle occurs in type 2 diabetic patients and in those at increased risk for this disorder, but the extent to which mitochondrial dysfunction in type 2 diabetic patients is remediable by physical activity and weight loss intervention is uncertain. We sought to address whether an intervention of daily moderate-intensity exercise combined with moderate weight loss can increase skeletal muscle mitochondrial content in type 2 diabetic patients and to address the relationship with amelioration of insulin resistance and hyperglycemia.


METHODS
Muscle biopsies were obtained before and after a 4-month intervention to assess mitochondrial morphology, mitochondrial DNA 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 Vo(2max) (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 A1C and fasting plasma glucose.


CONCLUSIONS
Intensive short-term lifestyle modifications can restore mitochondrial content and functional capacity in skeletal muscle in type 2 diabetic patients. The improvement in the oxidative capacity of skeletal muscle may be a key component mediating salutary effects of lifestyle interventions on hyperglycemia and insulin resistance.
Toledo
Frederico G S
FG
Division of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania , USA. toledofs@upmc.edu
Menshikova
Elizabeta V
EV
Ritov
Vladimir B
VB
Azuma
Koichiro
K
Radikova
Zofia
Z
DeLany
James
J
Kelley
David E
DE
D000328:Adult; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D005081:Exercise Therapy; D006801:Humans; D007328:Insulin / Q000097:blood; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000648:ultrastructure; D015431:Weight Loss
D001786:Blood Glucose; D007328:Insulin