Accelerated Neuromuscular Aging: Effect of Type 1 Diabetes on Muscle Function and Morphology

A team of investigators from McMaster University assessed the effect of aging on skeletal muscle function in individuals with and without type 1 diabetes.

As patients with type 1 diabetes (T1D) age, earlier onset of muscle weakness and fatigue can contribute to increasing frailty, muscle atrophy, and diminished muscle function, according to the results of a study published in The Journal of Clinical Endocrinology and Metabolism. These findings suggest that intervention prior to age 35, especially in young women with T1D, may be warranted to prevent loss of muscle strength and detrimental changes in muscle morphology.

Accelerated neuromuscular aging related to T1D occurs prior to development of the more typical affiliated comorbidities such as peripheral neuropathy, nephropathy, retinopathy, and cardiovascular disease. To study this further, a group of researchers from McMaster University, Dial and colleagues recruited adult 65 men and women (34 with T1D and 31 without diabetes). Participants were matched for age, biological sex, body mass index, and self-reported activity levels. Inclusion criteria specified that participants with T1D did not have confounding comorbidities – in particular, diabetic neuropathy.

Primary outcome measures included maximal voluntary contraction (MVC) testing, venous blood sampling, activity tracking, and a resting muscle biopsy for histologic/immunofluorescence analysis of muscle fiber types, glycogen content, and capillary density. 

Women older than 35 years with T1D were found to exhibit a moderate age-related decline in MVC force (-17%, g= -0.6) compared with a negligible decline in their disease-free counterparts (g = -0.2). Men older than 35 years with TID demonstrated a moderate age-related decline in MVC (-18%, g =-0.7) that was similar to the control group (-9%, g = -0.7). Overall, older participants with T1D exhibited a decline in MVC force production that was almost twice (~170%) that experienced by their control counterparts. No significant difference in capillary density was noted among patients with T1D vs the control group.

The investigators noted a sexual dimorphism related to skeletal muscle tissue morphology in T1D. Older women with T1D presented with a larger reduction in type 2 muscle fibers and a much higher quantity of type 1 fibers compared with age-matched controls. Conversely, men with T1D showed an increase in type 2 muscle fibers compared with age-matched controls. When analyzing hybrid muscle fiber types, men with T1D showed decreased 1/2 hybrid fiber type with no change in the 2AX hybrid type, whereas older women with T1D showed twice the amount of 2AX hybrid fiber types and thrice the amount of 1/2 hybrid fiber types. This evidence indicates that older women with T1D demonstrate accelerated neuromuscular aging more so than their male counterparts with T1D.

There was a strong negative correlation (r = -0.63; P <.01) between lower intramuscular glycogen content and increased sedentary activity levels in older adults with T1D. This may also indicate increased metabolic glycolysis during exercise and at rest in T1D.

Limitations to this study included fewer men than women in the study and lack of uniform measurements such as continuous glucose and activity monitoring, which was only conducted on older individuals with T1D as opposed to all study participants. As such, the investigators found it difficult to ascertain if differences in activity levels and blood glucose control influenced the mechanisms that contributed to the differences between the older and younger cohorts.

Thomas J. Hawke, PhD, commented on future research directions, stating: “We would like to interrogate the sex differences we have noted in this study in more detail.  Our subject population was generally well controlled and physically active, which is not representative of the full spectrum of those with T1D.  Being able to have a more broad range of subjects would provide us with more insight into the variables affecting muscle health and what factors are likely mediating the decline in muscle strength. We are particularly interested in whether those with T1D recover from intense exercise similarly to those without T1D.  Preclinical (mouse) models of T1D suggest there is a significant impairment in muscle regeneration, but this is completely unknown in humans with T1D.”

Dr Hawke recommended that “regular physical activity is safe and effective for most persons with T1D, and there should be strong advocacy for this by the healthcare team. [Routine] resistance exercise is a safe and effective means to mitigate strength loss in those with T1D.”


Dial AG, Monaco CMF, Grafham GK, Patel TP, Tarnopolsky MA, Hawke TJ. Impaired function and altered morphology in the skeletal muscles of adult men and women with type 1 diabetes. J Clin Endocrinol Metab. Published online April 23, 2021. doi:10.1210/clinem/dgab261