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

## TL;DR

This study shows that mitochondrial function in people with type 1 diabetes is not impaired when matched for fitness and other factors, emphasizing the role of exercise and healthy habits.

## Contribution

The study introduces a novel approach by matching type 1 diabetes patients and controls for cardiorespiratory fitness, revealing no mitochondrial impairment when this is considered.

## Key findings

- Maximal muscle mitochondrial respiration and density were similar between type 1 diabetes patients and healthy controls when matched for age, sex, BMI, and VO2max.
- Higher HbA1c levels in type 1 diabetes patients correlated with lower mitochondrial respiration, while higher BMI correlated with lower mitochondrial density.
- The study highlights the importance of exercise, glucose control, and BMI in maintaining mitochondrial health in type 1 diabetes.

## Abstract

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 (\documentclass[12pt]{minimal}
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\begin{document}$$\dot{V}{\text{O}}_{\text{2max}}$$\end{document}V˙O2max).

Seventeen individuals with type 1 diabetes and seventeen healthy control individuals matched for age, sex, BMI and \documentclass[12pt]{minimal}
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\begin{document}$$\dot{V}{\text{O}}_{\text{2max}}$$\end{document}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.

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\begin{document}$$\dot{V}{\text{O}}_{\text{2max}}$$\end{document}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.

Collectively, our study demonstrates that when matched for age, sex, BMI and \documentclass[12pt]{minimal}
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\begin{document}$$\dot{V}{\text{O}}_{\text{2max}}$$\end{document}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.

The online version of this article (10.1007/s00125-025-06451-1) contains peer-reviewed but unedited supplementary material.