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
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引用次数: 0
Abstract
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 (\(\dot{V}{\text{O}}_{\text{2max}}\)).
Methods
Seventeen individuals with type 1 diabetes and seventeen healthy control individuals matched for age, sex, BMI and \(\dot{V}{\text{O}}_{\text{2max}}\) 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
\(\dot{V}{\text{O}}_{\text{2max}}\) (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 \(\dot{V}{\text{O}}_{\text{2max}}\), 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.
目的/假设先前报道1型糖尿病骨骼肌线粒体功能降低的研究没有考虑到心肺健康，这是评估线粒体功能时的一个关键混杂因素。我们假设，与健康个体相比，1型糖尿病患者在年龄、性别、BMI和最大摄氧量匹配时，肌肉线粒体表型差异将被消除（\(\dot{V}{\text{O}}_{\text{2max}}\)）。方法17例1型糖尿病患者和17例年龄、性别、BMI和\(\dot{V}{\text{O}}_{\text{2max}}\)相匹配的健康对照者接受了股外侧肌活检。采用高分辨率呼吸仪评估线粒体呼吸，透射电镜评估线粒体密度和形态。结果\(\dot{V}{\text{O}}_{\text{2max}}\)(1型糖尿病患者40±10 kg−1 min−1；对照组41±8 ml kg−1 min−1；p=0.51)和线粒体氧化磷酸化能力(1型糖尿病患者101±35 [pmol O2] s−1 mg−1；对照组（99±23 [pmol O2] s−1 mg−1,p=0.82），组间差异无统计学意义。1型糖尿病患者的肌间纤维（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/interpretationCollectively, our study demonstrates that when matched for age, sex, BMI and \(\dot{V}{\text{O}}_{\text{2max}}\), 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
期刊介绍：
Diabetologia, the authoritative journal dedicated to diabetes research, holds high visibility through society membership, libraries, and social media. As the official journal of the European Association for the Study of Diabetes, it is ranked in the top quartile of the 2019 JCR Impact Factors in the Endocrinology & Metabolism category. The journal boasts dedicated and expert editorial teams committed to supporting authors throughout the peer review process.
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