title: Low dose prednisolone and insulin sensitivity differentially affect arterial stiffness and endothelial function: An open interventional and cross-sectional study.
abstract: Glucocorticoids could impair vascular function directly, or indirectly by reducing insulin sensitivity. The aim of this study was to determine the direct and indirect effects of acute and chronic low dose prednisolone on arterial stiffness and endothelial function.
  
  
  
  Twelve subjects with inflammatory arthritis, who had not taken oral glucocorticoids for ≥6 months, and 12 subjects with inflammatory arthritis, taking chronic (>6 months) low dose (6.3 ± 2.2 mg/day) prednisolone, were studied. Patients not on glucocorticoids underwent measurement of arterial stiffness (pulse wave velocity (PWV)) and endothelial function (reactive hyperaemia index (RHI)) before and after 7-10 days of prednisolone (6 mg/day), to assess the acute effects of prednisolone. Baseline data from patients not on glucocorticoids were compared with patients on long-term prednisolone to assess the chronic effects of prednisolone. Hepatic insulin sensitivity was estimated from percentage suppression of endogenous glucose production and peripheral insulin sensitivity as glucose infusion rate (M/I) during a hyperinsulinaemic-euglycaemic clamp.
  
  
  
  There were no significant changes in PWV with acute (9.2 ± 0.8 vs. 8.9 ± 0.8 m/sec, p = 0.33) or chronic (8.9 ± 0.8 vs. 9.0 ± 0.7 m/sec, p = 0.69) prednisolone. In multiple regression analysis, PWV was negatively associated with M/I during hyperinsulinemic-euglycemic clamp (p = 0.02), but not with suppression of endogenous glucose production (p = 0.15) or glucocorticoid use (p = 0.70). Chronic (2.4 ± 0.2 vs. 1.9 ± 0.1, p = 0.02), but not acute (1.8 ± 0.2 vs. 1.9 ± 0.1, p = 0.24), prednisolone resulted in a higher RHI.
  
  
  
  Arterial stiffness is not affected by low dose prednisolone per se, but is negatively associated with peripheral insulin sensitivity. Patients with rheumatoid arthritis taking long-term prednisolone had better endothelial function.
authors.affiliation: School of Medicine, Flinders University, Adelaide, Australia; Southern Adelaide Diabetes & Endocrine Services, Repatriation General Hospital, Adelaide, Australia.
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Petersons
authors.affiliation: Southern Adelaide Diabetes & Endocrine Services, Repatriation General Hospital, Adelaide, Australia.
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Mangelsdorf
authors.affiliation: Bioanalytical Mass Spectrometry Facility, Center for Healthy Brain Ageing and School of Medical Sciences, University of New South Wales, Sydney, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Poljak
authors.affiliation: Department of Rheumatology, Repatriation General Hospital, Adelaide, Australia.
authors.forename: Malcolm D
authors.initials: MD
authors.lastname: Smith
authors.affiliation: Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Sydney, Australia; Department of Endocrinology, St Vincent's Hospital, Sydney, Australia.
authors.forename: Jerry R
authors.initials: JR
authors.lastname: Greenfield
authors.affiliation: School of Medicine, Flinders University, Adelaide, Australia; Discipline of Medicine, University of Adelaide, Adelaide, Australia.
authors.forename: Campbell H
authors.initials: CH
authors.lastname: Thompson
authors.affiliation: School of Medicine, Flinders University, Adelaide, Australia; Southern Adelaide Diabetes & Endocrine Services, Repatriation General Hospital, Adelaide, Australia. Electronic address: morton.burt@sa.gov.au.
authors.forename: Morton G
authors.initials: MG
authors.lastname: Burt
mesh_terms: D000284:Administration, Oral; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D001786:Blood Glucose / Q000378:metabolism; D003430:Cross-Sectional Studies; D004334:Drug Administration Schedule; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000009:adverse effects; D015309:Glucose Clamp Technique; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage* / Q000009:adverse effects; D063177:Pulse Wave Analysis; D013997:Time Factors; D016896:Treatment Outcome; D059289:Vascular Stiffness / Q000187:drug effects*
chemical_list: D001786:Blood Glucose; D005938:Glucocorticoids; D007328:Insulin; D011239:Prednisolone
keywords: Glucocorticoids; Hyperinsulinemic-euglycemic clamp; Pulse wave velocity; Reactive hyperemia index