Active young adults with type 1 diabetes (T1D) possess mitochondrial and muscle ultrastructural abnormalities within their skeletal muscle, according to new findings in Diabetologia. Of note, these data suggest that recreational physical activity may be insufficient in preventing metabolic deficiencies in skeletal muscle in this population.
“A major clinical concern in this study is that the mitochondrial/metabolic alterations observed were in young adults with type 1 diabetes, who had self-reported moderate-to-vigorous activity levels above the American and Canadian diabetes associations’ recommendations,” wrote the investigators. “In addition, these changes occurred in large, proximal muscle groups without a detectable loss of capillary density.”
The effect of T1D on skeletal muscle ultrastructure was last reported several decades ago and has not been reported since the introduction of more aggressive types of insulin. The goal of the current study was to systematically assess skeletal muscle mitochondrial phenotype in a population of young adults with T1D.
The cohort included 12 physically active participants with T1D who were closely matched with 12 controls (for age, sex, body mass index, and level of physical activity), who underwent vastus lateralis muscle microbiopsies. Mitochondrial respiration, site-specific mitochondrial H2O2 emission and Ca2+ retention capacity (CRC) were all evaluated using permeabilized myofiber bundles.
Compared with controls, mitochondrial oxidative capacity was significantly lower in participants with T1D. This was observed specifically at Complex II of the electron transport chain, but there were no differences in mitochondrial content between the two groups. There was greater mitochondrial H2O2 emission at Complex III and decreased CRC in the muscles of participants with diabetes compared with the control group.
An increase in the size and number of autophagic remnants was observed in the muscles of participants with T1D. However, the levels of the autophagic regulatory protein, phosphorylated AMP-activated protein kinase (p-AMPKαThr172), and its downstream targets, phosphorylated Unc-51like autophagy activating kinase 1 (p-ULK1Ser555), and p62 did not differ in the two cohorts.
As noted by the investigators, the study is the first to demonstrate that there are site-specific alterations within the mitochondria of young adults with T1D compared with a control group. The data also show that alterations in mitochondrial bioenergetics occur in the absence of a loss of mitochondrial content or changes in skeletal muscle microvasculature. “Further investigation is required to identify the precise signaling pathway leading to these changes,” they wrote.
Monaco CMF, Hughes MC, Ramos SV, et al. Altered mitochondrial bioenergetics and ultrastructure in the skeletal muscle of young adults with type 1 diabetes [published online April 18, 2018]. Diabetologia. doi:10.1007/s00125-018-4602-6