OBJECTIVEType 2 diabetes is associated with insulin resistance and skeletal muscle mitochondrial dysfunction. We have found that subjects with early-onset type 2 diabetes show incapacity to increase Vo2max in response to chronic exercise. This suggests a defect in muscle mitochondrial response to exercise. Here, we have explored the nature of the mechanisms involved.RESEARCH DESIGN AND METHODSMuscle biopsies were collected from young type 2 diabetic subjects and obese control subjects before and after acute or chronic exercise protocols, and the expression of genes and/or proteins relevant to mitochondrial function was measured. In particular, the regulatory pathway peroxisome proliferator–activated receptor γ coactivator (PGC)-1α/mitofusin-2 (Mfn2) was analyzed.RESULTSAt baseline, subjects with diabetes showed reduced expression (by 26%) of the mitochondrial fusion protein Mfn2 and a 39% reduction of the α-subunit of ATP synthase. Porin expression was unchanged, consistent with normal mitochondrial mass. Chronic exercise led to a 2.8-fold increase in Mfn2, as well as increases in porin, and the α-subunit of ATP synthase in muscle from control subjects. However, Mfn2 was unchanged after chronic exercise in individuals with diabetes, whereas porin and α-subunit of ATP synthase were increased. Acute exercise caused a fourfold increase in PGC-1α expression in muscle from control subjects but not in subjects with diabetes.CONCLUSIONSOur results demonstrate alterations in the regulatory pathway that controls PGC-1α expression and induction of Mfn2 in muscle from patients with early-onset type 2 diabetes. Patients with early-onset type 2 diabetes display abnormalities in the exercise-dependent pathway that regulates the expression of PGC-1α and Mfn2.

Construction workers (CW) are at increased risk for a range of chronic diseases. We screened 983 CW for diabetes and cardiometabolic risk. The age range was 18-64 years, with mean age of 36.3 years. Self-reported questionnaires, Finnish diabetes risk score and fasting blood tests were collected at the workplace. The unadjusted prevalence of pre-diabetes and type 2 diabetes mellitus were 3.6% and 1.2%, respectively; 21% of CW had the metabolic syndrome (MetS). The majority were either overweight (48.3%) or obese (21.8%). In a regression model, age remained the strongest predictor of fasting glucose (p < 0.001). Pre-diabetes and diabetes mellitus were significantly associated with presence of the MetS [odds ratio (OR) 5.6; 95% confidence interval (CI): 2.8-11.5, p < 0.001 and OR 5.5; 95% CI: 1.6-18.7, p = 0.006, respectively]. Subjects engaged in greater physical activity outside of work had lower body mass index (26.9 vs. 28.8 kg/m(2), p = 0.03), waist circumference (95.8 vs. 98.1 cm, p = 0.03) and fasting serum triglycerides (1.1 vs. 1.4 mmol/L, p = 0.03) compared to those who were sedentary. Despite their youth and a physically demanding occupation, CW are at risk of cardiometabolic diseases. This risk increases with age and the MetS. Screening tools may be useful to identify those who are at risk.

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