A randomized intervention study to evaluate the effect of calcitriol therapy on the renin-angiotensin system in diabetes

Abstract

Background:Prior studies suggest that vitamin D therapy may decrease cardiovascular disease risk in type 2 diabetes (T2DM) by lowering renin-angiotensin system (RAS) activity. However, randomized human intervention studies to evaluate the effect of vitamin D receptor (VDR) agonists on RAS activity are lacking.Objective:The objective of this article is to investigate the effect of direct VDR activation with calcitriol on circulating RAS activity and vascular hemodynamics in T2DM.Methods:A randomized, double-blinded, and placebo-controlled study wherein 18 participants with well-controlled T2DM without chronic kidney disease (CKD) were administered calcitriol or placebo for three weeks was conducted. Outcome measures included plasma renin activity (PRA), serum and urinary aldosterone, mean arterial pressure (MAP) before and after an infusion of angiotensin II, and renal plasma flow (RPF) via para-aminohippurate clearance.Results:Despite an increase in 1,25(OH)2D with calcitriol administration (45.4 to 61.8 pg/ml, p = 0.03) and no change with placebo, there were no significant differences in PRA, serum or urinary aldosterone, baseline and angiotensin II-stimulated MAP, or basal and angiotensin II-stimulated RPF between interventions.Conclusion:In this randomized and placebo-controlled study in participants with T2DM without CKD, calcitriol therapy to raise 1,25(OH)2D levels, when compared with placebo, did not significantly change circulating RAS activity or vascular hemodynamics.

Vitamin D Analogs Can Retard the Onset or Progression of Diabetic Kidney Disease: A Systematic Review

“…The eight selected full-text original articles comprise three randomized controlled trials (22)(23)(24), a short-duration prospective study (25), and four cross-sectional studies (26)(27)(28)(29). The countries where these studies were conducted are located in North America (23,24), South America (25,26), Asia (27)(28)(29), and Europe (22). All the studies were hospitalbased.…”

“…One study reported a median age of 64 years (age range: 53-71years) in the intervention group and 61 years (age range: 51-71 years) in the placebo group (23). Additionally, their gender distribution shows that both sexes were equally distributed in one study (25), with female predominance in one study (26), and male predominance in the majority of the studies (22)(23)(24)(27)(28)(29). Using the Newcastle-Ottawa Scale, the methodological quality of four cross-sectional studies reveals a star-rating of < 7 (low quality) for one study (29), and ≥ 7 (high quality) for the rest of the studies (26)(27)(28).…”

Maintaining Optimum Health Requires Longer-Term Stable Vitamin D Concentrations

“…Vitamin D is an integral part of biology and physiology of human systems and to facilitate its beneficial, modulatory effects [17]. These include enzymatic reactions, mitochondrial function, subduing inflammation and oxidative stress, immune protection, secretion of hormones, such as insulin and PTH, and modulating the renin-angiotensin-aldosterone and FGF23-Klotho hormone systems [42]. In addition, metabolomics and transcriptomics advances will enable generation of improved longer-term extra-skeletal outcomes with targeted vitamin D therapy.…”

Uso da vitamina D para a diminuição do risco cardiovascular em pacientes com diabetes mellitus tipo II: Uma Revisão Sistemática

“…Após três semanas de intervenção, os níveis de 1,25 (OH)2D aumentou significativamente em pacientes que fizeram uso da suplementação de calcitriol, porém nada ocorreu naqueles que fizeram uso de placebo. Não houve diminuição do mecanismo renina-angiotensinaaldosterona, entretanto ocorreu um aumento na expressão de receptores de vitamina D (Zaheer et al, 2018).…”