Effect of acute and chronic glucocorticoid therapy on insulin sensitivity and postprandial vascular function

Radhakutty, Anjana; Mangelsdorf, Brenda L.; Drake, Sophie M.; Samocha-Bonet, Dorit; Jenkins, A. B.; Heilbronn, Leonie K.; Smith, Malcolm D.; Thompson, Campbell; Burt, Morton G.

doi:10.1111/cen.12966

Cited by 19 publications

(24 citation statements)

References 36 publications

(62 reference statements)

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“…With regard to the effect of GC therapy, certain studies reported a positive effect or the lack of effect on endothelial function in RA patients [14][15][16][17][18]. These discrepant results may be explained by the great heterogeneity in RA disease stage, dosages and treatment duration of GCs, or therapies Glucocorticoids and endothelial function in arthritis V C 2017 British Society for Immunology, Clinical and Experimental Immunology, 188: 208-218 associated with GCs among these studies.…”

Section: Discussionmentioning

confidence: 99%

“…Despite a significant evolution in the treatment of RA, the majority of patients still use GCs alone or in combination with diseasemodifying anti-rheumatic drugs (DMARDs). Regarding the endothelial function specifically, only five studies in RA investigated the effects of GCs on ED, and reported that GCs had no deleterious effect [14][15][16][17] or even beneficial effects on vascular function [18]. GCs might increase CV risk (CVR) by increasing CV risk factors (dyslipidaemia, hypertension, insulin resistance).…”

Section: Introductionmentioning

confidence: 99%

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Glucocorticoids improve endothelial function in rheumatoid arthritis: a study in rats with adjuvant-induced arthritis

Verhoeven

Totoson

Maguin‐Gaté

et al. 2017

Clinical and Experimental Immunology

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To determine the effect of glucocorticoids (GCs) on endothelial dysfunction (ED) and on traditional cardiovascular (CV) risk factors in the adjuvant-induced arthritis (AIA) rat model. At the first signs of AIA, a high dose (HD) [10 mg/kg/day, intraperitoneally (i.p.), GC-HD] or low dose (LD) (1 mg/kg/day, i.p., GC-LD) of prednisolone was administered for 3 weeks. Endothelial function was studied in aortic rings relaxed with acetylcholine (Ach) with or without inhibitors of nitric oxide synthase (NOS), cyclooxygenase 2 (COX-2), arginase, endothelium derived hyperpolarizing factor (EDHF) and superoxide anions ( O2-°) production. Aortic expression of endothelial NOS (eNOS), Ser1177-phospho-eNOS, COX-2, arginase-2, p22 and p47 was evaluated by Western blotting analysis. Arthritis scores, blood pressure, heart rate and blood levels of cytokines, triglycerides, cholesterol and glucose were measured. GC-HD but not GC-LD reduced arthritis score significantly and improved Ach-induced relaxation (P < 0·05). The positive effect of GC-HD resulted from increased NOS activity and EDHF production and decreased COX-2/arginase activities and O2-° production. These functional effects relied upon increased phospho-eNOS expression and decreased COX-2, arginase-2 and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase expression. Despite the lack of effect of GC-LD on ED, it increased NOS and EDHF and down-regulated O2-° pathways but did not change arginase and COX-2 pathways. GC-HD increased triglycerides levels and blood pressure significantly (P < 0·05). Both doses of GCs decreased to the same extent as plasma interleukin (IL)-1β and tumour necrosis factor (TNF)-α levels (P < 0·05). Our data demonstrated that subchronic treatment with prednisolone improved endothelial function in AIA via pleiotropic effects on endothelial pathways. These effects occurred independently of the deleterious cardiometabolic effects and the impact of prednisolone on systemic inflammation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Glucocorticoids improve endothelial function in rheumatoid arthritis: a study in rats with adjuvant-induced arthritis

Verhoeven

Totoson

Maguin‐Gaté

et al. 2017

Clinical and Experimental Immunology

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“…While most studies showed no deterioration of endothelial function after a treatment with a low dose or a bolus of GCs, one study reported improvement in endothelial function after 1 year of treatment with a low dose of a GC [48]. The effects of GCs are likely independent on disease duration [49]. Thus, despite the classical assumption that GCs are responsible for deterioration in endothelial function, no available data in the literature demonstrate such an effect in RA.…”

Section: Resultsmentioning

confidence: 99%

“…)Single doseCompared to baselineFMD3.3 % vs 3.1 % (NS)4Veselinovic et al [48]Serbia525.723.69 ± 0.84Prednisolone 7.5 mg/day (p.o.) + DMARDAt least 1 yearRA patients without GCFMD9.16 % ± 7.03 vs 12.6 % ± 5.49 P = 0.0057Radhakutty et al [49]Australia18--Prednisolone 6 mg/day (p.o. )7 daysRA patients taking prednisolone for 6 months (4–10 mg/day)PATNo effect7

GC glucocorticoid, RA rheumatoid arthritis, DAS28 disease activity score in 28 joints, DMARD disease-modifying antirheumatic drug, i.v .

…”

Section: Effects Of Gc On Endothelial Function In Ramentioning

confidence: 99%

“…Very recently, Radhakutty et al [49] aimed at comparing acute vs chronic treatment with GCs on post-prandial endothelial function in patients with RA. Microvascular endothelial function (assessed by PAT) was measured before and after a standardized meal, in 18 patients with RA (mean age 66 years), who were taking continuous oral prednisolone 4–10 mg/day for at least 6 months (chronic treatment) or 18 patients with RA (mean age 64 years) taking a 7-day course of oral prednisolone 6 mg/day (acute treatment).…”

Section: Effects Of Gc On Endothelial Function In Ramentioning

confidence: 99%

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Glucocorticoids and endothelial function in inflammatory diseases: focus on rheumatoid arthritis

et al. 2016

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Rheumatoid arthritis (RA) is the most common systemic autoimmune disease characterized by articular and extra-articular manifestations involving cardiovascular (CV) diseases. RA increases the CV mortality by up to 50 % compared with the global population and CV disease is the leading cause of death in patients with RA. There is growing evidence that RA favors accelerated atherogenesis secondary to endothelial dysfunction (ED) that occurs early in the course of the disease. ED is a functional and reversible alteration of endothelial cells, leading to a shift of the actions of the endothelium towards reduced vasodilation, proinflammatory state, proliferative and prothrombotic properties. The mechanistic links between RA and ED have not been fully explained, but growing evidence suggests a role for traditional CV factors, auto-antibodies, genetic factors, oxidative stress, inflammation and iatrogenic interventions such as glucocorticoids (GCs) use. GCs have been used in RA for several decades. Whilst their deleterious CV side effects were described in the 1950s, their effect on CV risk associated with inflammatory arthritis remains subject for debate. GC might induce negative effects on endothelial function, via a direct effect on endothelium or via increasing CV risk factors. Conversely, they might actually improve endothelial function by decreasing systemic and/or vascular inflammation. The present review summarizes the available data on the impact of GCs on endothelial function, both in normal and inflammatory conditions, with a special focus on RA patients.

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Effects of Selenium Supplementation on the Indices of Disease Activity, Inflammation and Oxidative Stress in Patients with Rheumatoid Arthritis: a Randomized Clinical Trial

Zamani,

Taghvaee,

Akbari

et al. 2023

Biol Trace Elem Res

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Effect of acute and chronic glucocorticoid therapy on insulin sensitivity and postprandial vascular function

Abstract: 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.

Cited by 19 publications

References 36 publications

Glucocorticoids improve endothelial function in rheumatoid arthritis: a study in rats with adjuvant-induced arthritis

Glucocorticoids improve endothelial function in rheumatoid arthritis: a study in rats with adjuvant-induced arthritis

Glucocorticoids and endothelial function in inflammatory diseases: focus on rheumatoid arthritis

Effects of Selenium Supplementation on the Indices of Disease Activity, Inflammation and Oxidative Stress in Patients with Rheumatoid Arthritis: a Randomized Clinical Trial

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