Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes.
Level 4 - case-series / case-control
Cross-sectional physiological study comparing three distinct human subject groups.
PubMed 12351431 · doi:10.2337/diabetes.51.10.2944
What was done
Percutaneous fasting biopsies of the vastus lateralis muscle were collected from 30 participants across three groups: lean nondiabetic volunteers (n = 10), obese nondiabetic volunteers (n = 10), and individuals with type 2 diabetes (n = 10). Researchers measured rotenone-sensitive NADH:O2 oxidoreductase activity in isolated mitochondrial fractions using alamethicin to allow substrate access. Enzyme activities were normalized to creatine kinase (myocyte marker) and citrate synthase (mitochondrial content marker). Mitochondrial morphology was assessed using electron microscopy.
What was found
Rotenone-sensitive NADH:O2 oxidoreductase activity normalized to creatine kinase was lowest in type 2 diabetic subjects and highest in lean controls (lean 0.95 ± 0.17, obese 0.76 ± 0.30, type 2 diabetes 0.56 ± 0.14 units/mU creatine kinase; P < 0.005). Citrate synthase activity was also significantly reduced in type 2 diabetes (lean 3.10 ± 0.74, obese 3.24 ± 0.82, type 2 diabetes 2.48 ± 0.47 units/mU creatine kinase; P < 0.005). Electron microscopy showed that skeletal muscle mitochondria were significantly smaller in type 2 diabetic and obese subjects than in lean volunteers (P < 0.01).
Why it matters
This study provides direct biochemical and structural evidence from human muscle tissue showing that impaired bioenergetic capacity and smaller mitochondrial size characterize skeletal muscle in type 2 diabetes.
Limits
The sample size is small with only 10 participants per group. The cross-sectional design cannot determine whether mitochondrial impairment is a cause or a consequence of insulin resistance and type 2 diabetes. The abstract does not report data on physical fitness levels, medication use, or demographic matching across groups.
Cited by
- supports People with type 2 diabetes have mitochondria that function roughly half as effectively as those in people without type 2 diabetes.