A Randomized Intervention Study to Evaluate the Effect of Vitamin D Receptor Agonist Therapy on the Renin-Angiotensin System in Diabetes

Presentation Number: SUN 336
Date of Presentation: April 2nd, 2017

Kiara Taquechel*1, Sarah Zaheer2, Jenifer Michelle Brown3, Jonathan S Williams4 and Anand Vaidya2
1Northeastern University, Boston, MA, 2Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 3Brigham and Women's Hospital, Harvard Medical School, MA, 4Brigham & Women's Hospital, Harvard Medical School, Boston, MA

Abstract

Context: Vitamin D deficiency has been associated with increased cardiovascular disease risk. Activation of the renin-angiotensin system (RAS) plays an important role in the development of cardiovascular disease, and both animal and human studies have suggested that activation of the vitamin D receptor (VDR) can decrease RAS activity.

Objective: We hypothesized that direct activation of the VDR with calcitriol could lower circulating RAS activity and improve vascular hemodynamics in type 2 diabetes.

Methods: We performed a randomized, double-blinded, and placebo-controlled intervention study wherein participants with well-controlled type 2 diabetes without chronic kidney disease (CKD) were administered calcitriol or placebo. Subjects were evaluated before and after 3 weeks of calcitriol 0.75 mcg daily (n=9) or placebo (n=9). Plasma renin activity (PRA) and serum and urinary aldosterone were measured under fixed conditions of dietary sodium restriction to assess maximal stimulation of the RAS before and after randomized interventions. Dietary potassium and calcium were also fixed and controlled. Mean arterial pressure (MAP) and renal plasma flow (RPF) via para-aminohippurate clearance were measured at rest, and before and after randomized interventions. Further, the MAP and RPF responses to an infusion of angiotensin II were measured. Two-way ANOVA with interaction modeling was used to assess the difference in effect between calcitriol and placebo on RAS, MAP, and RPF.

Results: Mean age, BMI, MAP, and kidney function were similar between the two randomized groups at baseline. A significant increase in 1,25(OH)2D levels was seen only in the calcitriol group post-intervention (45.4 to 61.8 pg/mL, P=0.03); serum calcium levels remained in the normal range. There was no significant change in maximally stimulated PRA (P=0.69), serum aldosterone (P=0.69), urinary aldosterone excretion (P=0.96), baseline MAP (P=0.49), or the MAP response to an infusion of angiotensin II (P=0.46) with either calcitriol or placebo. Similarly, neither calcitriol nor placebo influenced basal RPF (P=0.89) or the change in RPF in response to an infusion of angiotensin II (P=0.49).

Conclusion: In this randomized, double-blinded, and placebo-controlled study in participants with type 2 diabetes without CKD, direct activation of the VDR with calcitriol, when compared with placebo, did not significantly change circulating RAS activity or vascular hemodynamics.

 

Nothing to Disclose: KT, SZ, JMB, JSW, AV