TY - JOUR
T1 - Skeletal muscle mitochondrial health in type 1 diabetes
T2 - the role of exercise capacity and lifestyle factors
AU - Goulding, Richie P.
AU - Charlton, Braeden T.
AU - Breedveld, Ellen A.
AU - Huijts, Jelle Y.
AU - van der Laan, Matthijs
AU - Strating, Anne R.
AU - Noort, Wendy
AU - Kolodyazhna, Aryna
AU - Grootemaat, Anita E.
AU - Bloemers, Frank W.
AU - van der Wel, Nicole N.
AU - Wüst, Rob C. I.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/8
Y1 - 2025/8
N2 - 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.
AB - 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.
KW - Maximal oxygen uptake
KW - Mitochondrial density
KW - Mitochondrial respiration
KW - Muscle bioenergetics
KW - Muscle mitochondria
KW - Skeletal muscle
KW - Type 1 diabetes
UR - https://www.scopus.com/pages/publications/105005604547
U2 - 10.1007/s00125-025-06451-1
DO - 10.1007/s00125-025-06451-1
M3 - Article
C2 - 40399597
SN - 0012-186X
VL - 68
SP - 1823
EP - 1835
JO - Diabetologia
JF - Diabetologia
IS - 8
ER -
