Acute and chronic effects of low-dose prednisolone on carbohydrate metabolism in subjects with inflammatory rheumatologic disease. — ASN Events

Acute and chronic effects of low-dose prednisolone on carbohydrate metabolism in subjects with inflammatory rheumatologic disease. (#110)

Carolyn J Petersons 1 2 , Brenda L Mangelsdorf 1 , Arthur B Jenkins 3 , Anne Poljak 4 , Malcolm D Smith 2 5 , Jerry R Greenfield 3 6 , Campbell H Thompson 2 , Morton G Burt 1 2
  1. Southern Adelaide Diabetes and Endocrine Services, Repatriation General Hospital, Adelaide, SA, Australia
  2. Flinders University, Adelaide, SA, Australia
  3. Garvan Institute of Medical Research, Sydney, NSW, Australia
  4. Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, NSW, Australia
  5. Department of Rheumatology, Repatriation General Hospital, Adelaide, SA, Australia
  6. Department of Endocrinology, St Vincent's Hospital, Sydney, NSW, Australia

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 whether chronic prednisolone increased visceral adiposity, amplifying carbohydrate metabolism perturbations.
Nine subjects (4 female, age 58±11 years, BMI 27.5±5.8 kg/m2) with inflammatory rheumatologic disease not taking oral glucocorticoids were studied before and after prednisolone 6 mg/day for 7 days. Data were compared with 12 matched subjects (6 female, age 61±8 years, BMI 27.4±3.3 kg/m2) taking chronic (>6 months) prednisolone (6.3±2.2 mg/day). Hepatic glucose output was calculated from the change in isotopic enrichment of glucose after primed (5 mg/kg), continuous (3 mg/kg/hr) infusion of 6,6-2H2 glucose. Peripheral insulin sensitivity was assessed by hyperinsulinaemic-euglycaemic clamp (80 mU/m2/min for 120 minutes). Insulin secretion was determined by 60-minute frequently sampled intravenous glucose tolerance test (300 mg/kg glucose). Visceral adiposity was quantified by abdominal computed tomography.
Acute prednisolone administration increased hepatic glucose output (p=0.01) and reduced peripheral insulin sensitivity (p=0.02) and first- (p=0.01) and second-phase (p=0.02) insulin secretion (Table). There was no significant difference in visceral fat mass between subjects not on prednisolone and chronic prednisolone users (108±27 vs 97±11cm2, p=1.00). In subjects taking chronic prednisolone, hepatic glucose output was significantly greater (p=0.03) while insulin secretion was not significantly different from subjects not on prednisolone (Table). Peripheral insulin sensitivity was similar in chronic prednisolone users to following acute prednisolone administration (p=0.83) (Table).
In summary, acute low-dose prednisolone adversely affects all aspects of carbohydrate metabolism. However, in subjects taking chronic low-dose prednisolone increased hepatic glucose output is the major perturbation. Treatment of diabetes in patients on chronic low-dose prednisolone should primarily target a reduction in hepatic glucose output and also increase peripheral insulin sensitivity.


The study was supported by grants from the Diabetes Australia Research Trust and Foundation Daw Park. Dr Carolyn Petersons is supported by an Australian Postgraduate Award and Flinders Centre for Clinical Change and Health Care Research Scholarship. Dr Morton Burt is supported by a South Australian Health Practitioner Fellowship.