Effects of Low-Dose Prednisolone on Hepatic and Peripheral Insulin Sensitivity, Insulin Secretion, and Abdominal Adiposity in Patients With Inflammatory Rheumatologic Disease
- Carolyn J. Petersons, MBBS1,2⇑,
- Brenda L. Mangelsdorf, RN2,
- Arthur B. Jenkins, PHD3,4,
- Anne Poljak, PHD5,
- Malcolm D. Smith, PHD1,6,
- Jerry R. Greenfield, PHD3,7,
- Campbell H. Thompson, PHD1,8 and
- Morton G. Burt, PHD1,2
- 1Faculty of Health Sciences, Flinders University, Adelaide, Australia
- 2Southern Adelaide Diabetes and Endocrine Services, Repatriation General Hospital, Adelaide, Australia
- 3Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Sydney, Australia
- 4School of Health Sciences, University of Wollongong, Wollongong, Australia
- 5Bioanalytical Mass Spectrometry Facility and School of Medical Sciences, University of New South Wales, Sydney, Australia
- 6Department of Rheumatology, Repatriation General Hospital, Adelaide, Australia
- 7Department of Endocrinology, St. Vincent’s Hospital, Sydney, Australia
- 8Discipline of Medicine, University of Adelaide, Adelaide, Australia
- Corresponding author: Carolyn J. Petersons,
OBJECTIVES 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 6,6-2H2 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.
CONCLUSION 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.
- Received December 17, 2012.
- Accepted March 1, 2013.
- © 2013 by the American Diabetes Association.
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