Endocrine Abstracts

High dose glucocorticoids reduce hepatic and peripheral insulin sensitivity and insulin secretion. However, the metabolic consequences of typical therapeutic glucocorticoid doses (e.g. prednisolone <10 mg/day) are poorly characterised. The aim was to determine the acute effect of low dose prednisolone on carbohydrate metabolism and then assess whether subjects taking chronic prednisolone had increased adiposity that amplified carbohydrate metabolism perturbations.

Nine controls (4 female, age 58±11 years, BMI 27.5±5.8 kg/m²) with inflammatory rheumatologic disease who were not taking oral glucocorticoids were studied before and after prednisolone 6 mg/day for 7 days. Baseline data were compared with 12 matched subjects (6 female, age 61±8 years, BMI 27.4±3.3 kg/m²) taking long-term prednisolone (6.3±2.2 mg/day). Peripheral insulin sensitivity was assessed by hyperinsulinaemic–euglycaemic clamp (80 mU/m² per min for 120 min) and insulin secretion by 60 min intravenous glucose tolerance test (IVGTT, 25mg/kg glucose). Total and visceral adiposity were quantified by DXA and abdominal CT. Quantification of hepatic glucose output (using 6,6-²H₂ glucose) and insulin concentrations are underway (data to follow).

Glucose infusion rate during hyperinsulinaemic–euglycaemic clamp fell from 79.6±5.9 to 68.9±5.2 μmol/min per kg FFM (P=0.02) after 7 days of prednisolone. Glucose AUC during IVGTT acutely increased after prednisolone (504±14 to 579±19 mmol/L*min, P=0.01). There were no significant differences in total (27.8±2.8 vs 26.5±3.8 kg, P=0.78) or visceral (97±11 vs 108±27 cm², P=1.00) fat mass between chronic prednisolone users and controls. Glucose infusion rate during hyperinsulinaemic–euglycaemic clamp (68.7±6.6 vs 68.9±5.2 μmol/min per kg FFM, P=0.78) and glucose AUC during IVGTT (564±18 vs 579±19 mmol/l*min, P=0.67) were not significantly different in subjects taking chronic prednisolone and following acute prednisolone administration.

In conclusion, low dose prednisolone acutely reduces peripheral insulin sensitivity and may reduce insulin secretion. Perturbations of carbohydrate metabolism during chronic prednisolone therapy match those found acutely. These findings provide insight into targeting treatment of glucocorticoid-induced diabetes at the underlying metabolic abnormality.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.