Effect of acute and chronic glucocorticoid therapy on insulin sensitivity and postprandial vascular function.
OBJECTIVE
Postprandial hyperglycaemia is associated with increased arterial stiffness and cardiovascular events. Low-dose prednisolone causes insulin resistance that typically manifests as postprandial hyperglycaemia. We investigated whether prednisolone causes postprandial vascular dysfunction in a cohort of patients with rheumatoid arthritis.


METHODS
An open interventional and cross-sectional study was undertaken.


METHODS
Eighteen subjects with rheumatoid arthritis who had not taken oral glucocorticoids for ≥6 months were studied before and after prednisolone 6 mg/day for 7 days to determine the acute effects of prednisolone. Pre-prednisolone data were compared to 18 subjects with rheumatoid arthritis taking long-term (>6 months) prednisolone (6·5 ± 1·8 mg/day) to assess the chronic effects of prednisolone. Augmentation index (by applanation tonometry) and reactive hyperaemia index (by peripheral artery tonometry) were measured before and after a mixed-meal (10 kcal/kg, 45% carbohydrate, 15% protein, 40% fat). Insulin sensitivity was estimated by the Matsuda index and sympathetic nervous system activity from urinary noradrenaline excretion.


RESULTS
Matsuda index was lower after acute (2·0 ± 1·0 vs 3·6 ± 1·1, P = 0·01) and chronic (1·9 ± 1·0 vs 3·6 ± 1·1, P = 0·04) prednisolone. Postprandial augmentation index was lower after acute prednisolone (2551 ± 197 vs 2690 ± 272%*min, P ≤ 0·001), but not chronic prednisolone. There were no significant differences in reactive hyperaemia index with acute or chronic prednisolone. Noradrenaline excretion was lower after acute (54 ± 8 vs 93 ± 23 nmol/6 h, P = 0·02), but not chronic, prednisolone.


CONCLUSIONS
Prednisolone-induced insulin resistance is not associated with postprandial vascular dysfunction in patients with rheumatoid arthritis. Reduced sympathetic activity may contribute to the reduction in postprandial arterial stiffness with acute prednisolone.
School of Medicine, Flinders University, Adelaide, Australia.|Southern Adelaide Diabetes and Endocrine Services, Repatriation General Hospital, Adelaide, Australia.
Anjana
A
Radhakutty
Southern Adelaide Diabetes and Endocrine Services, Repatriation General Hospital, Adelaide, Australia.
Brenda L
BL
Mangelsdorf
Southern Adelaide Diabetes and Endocrine Services, Repatriation General Hospital, Adelaide, Australia.
Sophie M
SM
Drake
Diabetes & Metabolism Division, Garvan Institute of Medical Research, Sydney, Australia.
Dorit
D
Samocha-Bonet
Diabetes & Metabolism Division, Garvan Institute of Medical Research, Sydney, Australia.|School of Medicine, University of Wollongong, Wollongong, Australia.
Arthur B
AB
Jenkins
Discipline of Medicine, The University of Adelaide, Adelaide, Australia.
Leonie K
LK
Heilbronn
School of Medicine, Flinders University, Adelaide, Australia.|Department of Rheumatology, Repatriation General Hospital, Adelaide, Australia.
Malcolm D
MD
Smith
School of Medicine, Flinders University, Adelaide, Australia.|Discipline of Medicine, The University of Adelaide, Adelaide, Australia.
Campbell H
CH
Thompson
School of Medicine, Flinders University, Adelaide, Australia.|Southern Adelaide Diabetes and Endocrine Services, Repatriation General Hospital, Adelaide, Australia.
Morton G
MG
Burt
D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D001786:Blood Glucose / Q000032:analysis*; D003430:Cross-Sectional Studies; D004334:Drug Administration Schedule; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000627:therapeutic use; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000503:physiopathology; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D011239:Prednisolone / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D059289:Vascular Stiffness / Q000187:drug effects
D001786:Blood Glucose; D005938:Glucocorticoids; D011239:Prednisolone