Ectopic fat in the liver and pancreas is a well-recognised contributor to insulin resistance, but other factors can often significantly contribute to diabetes risk. For instance, skeletal muscle is responsible for about 80% of glucose uptake, although it remains under-appreciated in the pathogenesis of diabetes.

Motohashi et al. report two brothers with Becker muscular dystrophy, both with significant skeletal muscle degeneration but different glycaemic outcomes. The younger sibling developed diabetes following heart transplantation and immunosuppressive therapy (tacrolimus and everolimus). His brother maintained impaired glucose tolerance without progressing to diabetes. Despite similar degrees of muscle loss and fat accumulation (body mass index 25.9 and 26.4kg/m², body fat mass 46.2% and 50.7%), only the post-transplant case showed β-cell dysfunction. He had low HOMA-β (homeostasis model assessment of β-cell function) at 36.5%, and high HOMA-IR (homeostasis model assessment of insulin resistance) at 2.48, probably triggered by immunosuppressive agents. Treatment with metformin and dulaglutide achieved glycaemic control.

This highlights the synergistic effect of skeletal muscle loss and β-cell stress in tipping the metabolic balance towards diabetes, even in the absence of classical risk factors such as obesity. For clinicians managing muscular dystrophy or other muscle-wasting conditions, particularly in post-transplant settings, vigilance for diabetes is warranted even when traditional metabolic markers seem modest.

Read the full article in Endocrinology, Diabetes & Metabolism Case Reports https://doi.org/10.1530/EDM-25-0038