Reduced Skeletal Muscle Uncoupling Protein-3 Content in Prediabetic Subjects and Type 2 Diabetic Patients: Restoration by Rosiglitazone Treatment

Context: The mitochondrial uncoupling protein-3 (UCP3) has been implicated in the protection of the mitochondrial matrix against lipid-induced mitochondrial damage. Recent evidence points toward mitochondrial aberrations as a major contributor to the development of insulin resistance and diabetes, and UCP3 is reduced in diabetes.
Objective: We compared skeletal muscle UCP3 protein levels in prediabetic subjects [i.e. impaired glucose tolerance (IGT)], diabetic patients, and healthy controls and examined whether rosiglitazone treatment was able to restore UCP3.
Patients, Design, Intervention: Ten middle-aged obese men with type 2 diabetes mellitus [age, 61.4 ± 3.1 yr; body mass index (BMI), 29.8 ± 2.9 kg/m2], nine IGT subjects (age, 59.0 ± 6.6 yr; BMI, 29.7 ± 3.0 kg/m2), and 10 age- and BMI-matched healthy controls (age, 57.3 ± 7.4 yr; BMI, 30.1 ± 3.9 kg/m2) participated in this study. After baseline comparisons, diabetic patients received rosiglitazone (2 x 4 mg/d) for 8 wk.
Main Outcome Measures: Muscle biopsies were sampled to determine UCP3 and mitochondrial protein (complex I–V) content.
Results: UCP3 protein content was significantly lower in prediabetic IGT subjects and in diabetic patients compared with healthy controls (39.0 ± 28.5, 47.2 ± 24.7, and 72.0 ± 23.7 arbitrary units, respectively; P < 0.05), whereas the levels of the mitochondrial protein complex I–V were similar between groups. Rosiglitazone treatment for 8 wk significantly increased insulin sensitivity and muscle UCP3 content (from 53.2 ± 29.9 to 66.3 ± 30.9 arbitrary units; P < 0.05).
Conclusion: We show that UCP3 protein content is reduced in prediabetic subjects and type 2 diabetic patients. Eight weeks of rosiglitazone treatment restores skeletal muscle UCP3 protein in diabetic patients.

Effects of high-intensity progressive resistance training on self-reported health status in older persons with type 2 diabetes

Purpose: To evaluate the influence of high-intensity progressive resistance training (PRT) on self-reported physical and mental health in older persons with type 2 diabetes.

Methods: We performed a 12-month RCT with 36 overweight men and women with type 2 diabetes (aged 60-80 years) who were randomly assigned to a moderate weight-loss diet plus PRT (PRT&WL) or a moderate weight-loss diet plus a control (stretching) program (WL). Gymnasium-based training for 6 months was followed by an additional 6 months of home-based training. The SF-36 (v1) questionnaire was used to obtain physical (PCS) and mental (MCS) health component summary scores at baseline, 6 and 12 months.

Results: Subject retention was 81% and 72% after 6 and 12 months respectively. Exercise adherence during gymnasium- and home-based training was 88% and 73% for the PRT&WL group, and 85% and 78.1% for the WL group respectively. In a regression model adjusted for age and sex, PCS improved in the PRT&WL group compared to the WL group after 6 months of gymnasium-based training (2.3 versus -2.0, p = 0.05), which persisted after 12 months training (0.7 versus -4.1, p = 0.03). There were no between-group differences at 6 or 12 months for the MCS.

Conclusion: High-intensity PRT was effective in improving self-reported physical health, but not mental health. PRT provides an effective exercise alternative in lifestyle management for older adults with type 2 diabetes.