Effect of short-term prednisone on beta-cell function in subjects with type 2 diabetes mellitus and healthy subjects

Abstract

Objective For those with type 2 diabetes mellitus (T2DM), impact of short-term high-dose glucocorticoid exposure on beta-cell function is unknown. This study aims to compare the impact on beta-cell function and insulin resistance of prednisone 40 mg between adults with newly diagnosed T2DM and healthy adults. Methods Five adults with T2DM and five healthy adults, all between 18–50 years, were enrolled. T2DM diagnosis was less than one year prior, HbA1c<75 mmol/mol (9.0%), with metformin treatment only. Pre- and post-therapy testing included 75-g oral glucose tolerance, plasma glucose, C-peptide, and insulin. Intervention therapy was prednisone 40mg daily for 3 days. Results Upon therapy completion, HOMA-IR did not increase or differ between groups. Percentile difference for HOMA-%B and insulinogenic index in those with T2DM was significantly lower statistically (50.4% and 69.2% respectively) compared to healthy subjects (19% and 32.2%). Conclusions Contrary to the assumption that insulin resistance is the main driver of glucocorticoid-induced hyperglycemia, results indicate that decreased beta-cell insulin secretion is the more likely cause in those with T2DM. This is evidenced by significant drops in C-peptide AUC and HOMA-%B and increased glucose AUC in T2DM group only. These results may be caused by increased beta-cell fragility along with reduced recovery ability after glucocorticoid exposure. ClinicalTrials.gov NCT03661684.