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 (<InlineEquation ID="IEq1"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="125_2025_6451_Article_IEq1.gif" Format="GIF" Height="20" Rendition="HTML" Resolution="72" Type="Linedraw" Width="56" /> </InlineMediaObject> <EquationSource Format="TEX">$\dot{V}{\text{O}}_{\text{2max}}$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mover accent="true"> <mi>V</mi> <mo>˙</mo> </mover> <msub> <mtext>O</mtext> <mtext>2max</mtext> </msub> </mrow> </math></EquationSource> </InlineEquation>). Methods Seventeen individuals with type 1 diabetes and seventeen healthy control individuals matched for age, sex, BMI and <InlineEquation ID="IEq2"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="125_2025_6451_Article_IEq1.gif" Format="GIF" Height="20" Rendition="HTML" Resolution="72" Type="Linedraw" Width="56" /> </InlineMediaObject> <EquationSource Format="TEX">$\dot{V}{\text{O}}_{\text{2max}}$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mover accent="true"> <mi>V</mi> <mo>˙</mo> </mover> <msub> <mtext>O</mtext> <mtext>2max</mtext> </msub> </mrow> </math></EquationSource> </InlineEquation> 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 <InlineEquation ID="IEq3"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="125_2025_6451_Article_IEq1.gif" Format="GIF" Height="20" Rendition="HTML" Resolution="72" Type="Linedraw" Width="56" /> </InlineMediaObject> <EquationSource Format="TEX">$\dot{V}{\text{O}}_{\text{2max}}$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mover accent="true"> <mi>V</mi> <mo>˙</mo> </mover> <msub> <mtext>O</mtext> <mtext>2max</mtext> </msub> </mrow> </math></EquationSource> </InlineEquation> (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 <InlineEquation ID="IEq4"> <InlineMediaObject> <ImageObject Color="BlackWhite" FileRef="125_2025_6451_Article_IEq1.gif" Format="GIF" Height="20" Rendition="HTML" Resolution="72" Type="Linedraw" Width="56" /> </InlineMediaObject> <EquationSource Format="TEX">$\dot{V}{\text{O}}_{\text{2max}}$</EquationSource> <EquationSource Format="MATHML"><math> <mrow> <mover accent="true"> <mi>V</mi> <mo>˙</mo> </mover> <msub> <mtext>O</mtext> <mtext>2max</mtext> </msub> </mrow> </math></EquationSource> </InlineEquation>, 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. Graphical Abstract

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

期刊论文
出版模式：

开放获取
发表日期：

2025年5月21日

查看全文

Richie P. Goulding,
Braeden T. Charlton,
Ellen A. Breedveld,
Jelle Y. Huijts,
Matthijs van der Laan,
Anne R. Strating,
Wendy Noort,
Aryna Kolodyazhna,
Anita E. Grootemaat,
Frank W. Bloemers,
Nicole N. van der Wel,
Rob C. I. Wüst

摘要

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 ( $\dot{V}{\text{O}}_{\text{2max}}$ $\dot{V} O_{2max}$ ).

Methods

Seventeen individuals with type 1 diabetes and seventeen healthy control individuals matched for age, sex, BMI and $\dot{V}{\text{O}}_{\text{2max}}$ $\dot{V} O_{2max}$ 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

$\dot{V}{\text{O}}_{\text{2max}}$ $\dot{V} O_{2max}$ (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 HbA_1c displayed lower rates of mitochondrial respiration than those with lower HbA_1c, 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 $\dot{V}{\text{O}}_{\text{2max}}$ $\dot{V} O_{2max}$ , 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.

Graphical Abstract