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

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 macro-albuminuria 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.