Skeletal muscle mitochondrial health in type 1 diabetes: the role of exercise capacity and lifestyle factors

Aims/hypothesis: Previous studies reporting lower skeletal muscle mitochondrial function in type 1 diabetes did not account for cardiorespiratory fitness, a key confounder when assessing mitochondrial function. We hypothesised that, compared with healthy individuals, muscle mitochondrial phenotypic differences would be abolished in individuals with type 1 diabetes when matched for age, sex, BMI and maximal oxygen uptake (V˙O2max). Methods: Seventeen individuals with type 1 diabetes and seventeen healthy control individuals matched for age, sex, BMI and V˙O2max participated and underwent a muscle biopsy from the vastus lateralis. Mitochondrial respiration was assessed by high-resolution respirometry, and mitochondrial density and morphology were assessed by transmission electron microscopy. Results: V˙O2max (individuals with type 1 diabetes 40±10 kg−1 min−1; control individuals 41±8 ml kg−1 min−1; p=0.51) and mitochondrial oxidative phosphorylation capacity (individuals with type 1 diabetes 101±35 [pmol O2] s−1 mg−1; control individuals 99±23 [pmol O2] s−1 mg−1, p=0.82) did not differ between groups. Both intermyofibrillar (individuals with type 1 diabetes 6.07±2.16%; control individuals 6.01±1.11%; p=0.92) and subsarcolemmal (individuals with type 1 diabetes 18.70±8.16%; control individuals 19.29±7.36%; p=0.83) mitochondrial densities were not different between groups. Mitochondrial respiration normalised by density did not differ between groups. However, individuals with type 1 diabetes and higher HbA1c displayed lower rates of mitochondrial respiration than those with lower HbA1c, whereas those with higher BMI displayed lower mitochondrial densities than those with lower BMI. Conclusions/interpretation: Collectively, our study demonstrates that when matched for age, sex, BMI and V˙O2max, maximal muscle mitochondrial respiration and morphology in people with type 1 diabetes are not impaired. These findings highlight the importance of habitual exercise, optimal glucose management and a healthy BMI in maintaining mitochondrial health in individuals with type 1 diabetes.