Muscle Cell Profiles Relate to Exercise Response Variation in Type 2 Diabetes

Individuals with type 2 diabetes experience exercise training response variations that may have a cell-autonomous underpinning that can be seen in distinct basal myocellular epigenomic muscle tissue profiles, some of which are sustained in primary skeletal muscle cells, according to a study published in Diabetes Care.

Researchers in the current study analyzed data to identify potential mechanisms underlying the variations of response to exercise training in patients with type 2 diabetes. Specifically, researchers aimed to determine whether variations in phosphocreatine recovery rates were marked by distinct epigenomic muscle profiles that could be seen prior to training.

Seventeen participants with type 2 diabetes were classified as responders (n=11), or non-responders (n=6) to exercise training based on changes in recovery rate of phosphocreatine after 10 weeks of aerobic training. Researchers measured pre- and post-training phosphocreatine recovery rates, muscle mitochondrial function, insulin sensitivity, blood profiles, and aerobic capacity. 

They also performed muscle biopsies in vastus lateralis before training to isolate primary skeletal muscle cells for the assessment of RNA sequences and global DNA methylation in muscle tissue and skeletal muscle cells.

Training responders increased and non-responders decreased phosphocreatine recovery rates with aerobic training. Glycemic control (as measured by HbA1c) worsened post-training in non-responders, and insulin sensitivity (M-value; hyperinsulinemic-euglycemic clamp) did not improve, while insulin sensitivity did improve in responders. Both groups showed a 12% improvement in aerobic capacity (as measured by VO_2peak). Responders and non-responders were distinguished by differences in molecular muscle tissue and primary skeletal muscle cell patterns (RNA expression and DNA methylation). Elevations in insulin signaling, glutathione regulation, and mitochondrial metabolism were identified pre-training in non-responders via enrichment analyses and were also reflected in vivo by higher insulin sensitivity and phosphocreatine recovery rates pretraining.

Study investigators conclude that because epigenomic profile differences were also seen in myogenic progenitor cells, the variations in training response seen in patients with type 2 diabetes are likely cell autonomous. They noted that their data “provide new evidence to potentially shift the diabetes treatment paradigm by identifying individuals that do not reap metabolic benefits from exercise training, such that supplemental treatment options can be designed.”

Reference

Stephens NA, Brouwers B, Eroshkin AM, et al. Exercise response variations in skeletal muscle PCr recovery rate and insulin sensitivity relate to muscle epigenomic profiles in individuals with type 2 diabetes [published online August 2, 2018]. Diabetes Care. pii:dc180296. doi:10.2337/dc18-0296