Twenty-four-hour profiles of plasma glucose, insulin, C-peptide and free fatty acid in subjects with varying degrees of glucose tolerance following short-term, medium-dose prednisone (20 mg/day) treatment: evidence for differing effects on insulin secretion and action

Abstract

Objective: To determine the time course and prandial effects of short-term, medium-dose prednisone on 24-h metabolic patterns under standardized conditions.

Context: Glucocorticoids (GCs) adversely affect glucose homoeostasis but 24-h profiles of glucose, insulin, C-peptide and free fatty acids (FFAs) following short-term, medium-dose prednisone treatment in persons with varying degrees of glucose tolerance are not well defined.

Design: An open-label cross-sectional interventional study.

Subjects: Three groups were prospectively studied: persons with type 2 diabetes (T2DM; n = 7), persons 'at risk' for T2DM (AR; n = 8) and persons with normal glucose tolerance (NGT; n = 5).

Methods: Before and after 3-day treatment with prednisone 20 mg each morning, subjects underwent 24-h frequent blood sampling. Eucaloric mixed meals were provided at 08:00, 12:00 and 18:00 h. Insulin/glucose ratio provided an estimate of β-cell response to meal stimuli.

Measurements: Plasma glucose, insulin, C-peptide, haemoglobin A1c and FFA.

Results: Prednisone induced greater increases in glucose levels from midday (P = 0·001) to midnight (P = 0·02) in the T2DM than the AR and NGT groups. In contrast, insulin (P = 0·03) and C-peptide (P = 0·04) levels decreased postbreakfast in the T2DM group, whereas no changes in the morning but higher C-peptide levels (P = 0·03) from midday to midnight were observed in the AR group. In the T2DM group, insulin/glucose ratio decreased postbreakfast (P = 0·04) and increased postdinner (P = 0·03). Fasting glucose, insulin and C-peptide levels were unchanged in all groups, and FFA levels modestly increased postdinner (P = 0·03) in the NGT group.

Conclusion: Short-term, medium-dose prednisone treatment induces postprandial hyperglycaemia in T2DM and AR predominantly from midday to midnight because of suppression of insulin secretion followed by decreased insulin action that dissipates overnight. Effective treatment of prednisone-induced hyperglycaemia should target both rapid onset relative insulin deficiency and a less than 24-h total duration of effect.