Publications

Abstract

OBJECTIVE: The metabolic effects of low-dose prednisolone and optimal management of glucocorticoid-induced diabetes are poorly characterized. The aims were to investigate the acute effects of low-dose prednisolone on carbohydrate metabolism and whether long-term low-dose prednisolone administration increases visceral adiposity, amplifying metabolic perturbations. RESEARCH DESIGN AND METHODS: Subjects with inflammatory rheumatologic disease without diabetes mellitus were recruited. Nine subjects (age, 59 +/- 11 years) not using oral glucocorticoids were studied before and after a 7- to 10-day course of oral prednisolone 6 mg daily. Baseline data were compared with 12 subjects (age, 61 +/- 8 years) using continuous long-term prednisolone (6.3 +/- 2.2 mg/day). Basal endogenous glucose production (EGP) was estimated by 6,6-(2)H2 glucose infusion, insulin sensitivity was estimated by two-step hyperinsulinemic-euglycemic clamp, insulin secretion was estimated by intravenous glucose tolerance test, and adipose tissue areas were estimated by computed tomography. RESULTS: Prednisolone acutely increased basal EGP (2.44 +/- 0.46 to 2.65 +/- 0.35 mg/min/kg; P = 0.05) and reduced insulin suppression of EGP (79 +/- 7 to 67 +/- 14%; P = 0.03), peripheral glucose disposal (8.2 +/- 2.4 to 7.0 +/- 1.6 mg/kg/min; P = 0.01), and first-phase (5.9 +/- 2.0 to 3.9 +/- 1.6 mU/mmol; P = 0.01) and second-phase (4.6 +/- 1.7 to 3.6 +/- 1.4 mU/mmol; P = 0.02) insulin secretion. Long-term prednisolone users had attenuated insulin suppression of EGP (66 +/- 14 vs. 79 +/- 7%; P = 0.03) and nonoxidative glucose disposal (44 +/- 24 vs. 62 +/- 8%; P = 0.02) compared with nonglucocorticoid users, whereas basal EGP, insulin secretion, and adipose tissue areas were not significantly different. CONCLUSIONS: Low-dose prednisolone acutely perturbs all aspects of carbohydrate metabolism. Long-term low-dose prednisolone induces hepatic insulin resistance and reduces peripheral nonoxidative glucose disposal. We conclude that hepatic and peripheral insulin sensitivity should be targeted by glucose-lowering therapy for glucocorticoid-induced diabetes.