High-Protein Diet Prevents Glucocorticoid-Induced Fat Mass Accumulation and Hyperglycemia

Glucocorticoid-induced diabetes is the most common form of drug-induced hyperglycemia. In addition, chronic exposure to glucocorticoids promotes lean mass loss and fat mass accumulation. In this study, we hypothesized that a high-protein diet (60% kcal; HPD) would help to offset sarcopenia during oral administration of corticosterone to C57BL/6J mice. Carbohydrates were reduced in the HPD to ensure it was isocaloric with the normal-protein diet (20% kcal; NPD). We found that the HPD prevented fat mass accumulation but did not protect against reductions in lean mass in both male and female mice. Mice consuming a HPD did not develop hyperglycemia, while mice given the NPD developed hyperglycemia within two weeks. The HPD diet did not improve insulin sensitivity in response to glucocorticoids but did alter gene expression patterns in adipose tissue and liver measured by RNA sequencing. We conclude that a HPD diet may be beneficial to limit rises in blood glucose and adipose tissue accrual during glucocorticoid therapy.