Association of Circulating Vitamin D, VDBP, and Vitamin D Receptor Expression with Severity of Diabetic Nephropathy in a Group of Saudi Type 2 Diabetes Mellitus Patients

Abstract

Background: As the seventh leading cause of death by 2030, type 2 diabetes mellitus (T2DM) is considered the most common chronic metabolic disease worldwide. Vitamin D metabolic axis players were identified as good candidates for T2DM. We aimed to analyze the circulating levels of total 25-hydroxy vitamin D (25-OHD), vitamin D receptor (VDR) transcript and VD-binding protein (VDBP) in a sample of Saudi T2DM and to correlate these profiles with diabetic nephropathy and insulin resistance.

Methods: Ninety T2DM patients, classified into normo-, micro- and macro-albuminuria groups (n = 30/each) and 50 healthy controls were studied. Serum (25-OHD) and VDBP levels were assayed by ELISA. The peripheral blood mononuclear cell (PBMN) VDR expression level was quantified by real-time RT-PCR. Insulin resistance was evaluated by the homeostasis model assessment index (HOMAI).

Results: The normo-albuminuria group showed the highest levels of PBMN VDR expression, whereas the macroalbuminuria group had the lowest levels among T2DM patients. However, serum VDBP levels were significantly elevated in all patient groups. There was a significant positive correlation between PBMN VDR expression levels and serum (25-OHD) in the total patient group (r = 0.579, p < 0.001). Spearman's correlation showed significant correlations of the circulatory markers with many clinico-laboratory variables. Stepwise regression analysis indicated that serum VDBP levels, HBA1c, and BMI were independent predictors for albuminuria.

Conclusions: The study findings suggest a potential role of vitamin D metabolic players in DN, with a special concern regarding serum VDPB as a putative predictor of DN severity in type 2 DM Saudi patients. Large-scale validation studies are warranted.