Levels of Serum 25(OH)VD₃, HIF-1α, VEGF, vWf, and IGF-1 and Their Correlation in Type 2 Diabetes Patients with Different Urine Albumin Creatinine Ratio

Abstract

Objective. To investigate changes in serum 25(OH)VD3, HIF-1α, VEGF, vWf, IGF-1, and their correlation in type 2 diabetes patients at different stages of diabetic kidney disease (DKD). Methods. 502 type 2 diabetes patients were divided into three groups: Normoalbuminuric group (201 patients), Microalbuminuric group (171 patients), and Macroalbuminuric group (130 patients). Serum 25-hydroxyvitamin D3 [25(OH)VD3] was measured by chemiluminescence. Serum hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), von Willebrand factor (vWf), and insulin-like growth factor-1 (IGF-1) were determined by enzyme-linked immunosorbent assay. We detected the aforementioned serum factors in all cases and 224 control subjects. Results. Serum HIF-1α, VEGF, vWf, and IGF-1 in type 2 diabetes patients were significantly higher than those in the control group and increased with the increase of Ln(ACR), respectively (P < 0.001). Serum 25(OH)VD3 was significantly lower in type 2 diabetes patients and decreased with the increase of Ln(ACR) (P < 0.001). Ln(ACR) was positively correlated with duration, HbA1c, Scr, BUN, TC, LDL, TG, UA, HIF-1α, VEGF, IGF-1, vWf, and Fg and negatively correlated with 25(OH)VD3 and eGFR. Conclusion. Serum HIF-1α, VEGF, vWf, and IGF-1 may be involved in DKD process through inflammation, angiogenesis, and endothelial injury. Serum 25(OH)VD3 may have protective effects on DKD partly by inhibiting inflammation, abnormal angiogenesis, and vascular endothelial dysfunction.

Vitamin D Decreases Serum VEGF Correlating with Clinical Improvement in Vitamin D-Deficient Women with PCOS: A Randomized Placebo-Controlled Trial

“…Our findings, showing a significant decrease in VEGF following vitamin D treatment, are consistent with multiple previous studies [19,21,22,27,28]. In fact, Shao et al have recently shown that serum 25OH-D3 negatively correlates with VEGF in diabetic patients; such correlation suggests that the protective effects of vitamin D in terms of decreasing proteinuria and delaying the progression of diabetic kidney disease may be mediated through its suppression of abnormal angiogenesis, inflammation, and vascular endothelial dysfunction [19].…”

“…In fact, Shao et al have recently shown that serum 25OH-D3 negatively correlates with VEGF in diabetic patients; such correlation suggests that the protective effects of vitamin D in terms of decreasing proteinuria and delaying the progression of diabetic kidney disease may be mediated through its suppression of abnormal angiogenesis, inflammation, and vascular endothelial dysfunction [19]. Moreover, Ren et al have confirmed that 1,25(OH) 2 -D3 downregulates the expression of VEGF in the retinal tissues of diabetic rats, thereby protecting them against diabetic retinopathy [28].…”

Morphometric and histopathological evaluation of the effect of grape seed proanthocyanidin on alveolar bone loss in experimental diabetes and periodontitis

“…Under hypoxic conditions such as in diabetes mellitus, HIF‐1α accumulates and induces expressions of certain factors including VEGF . Diabetes also elevated HIF‐1α and VEGF levels and increased levels were found related to diabetic kidney disease . In contrast, Sunkari et al found that HIF‐1α levels decreased in diabetic wounds in mice and hyperbaric oxygen therapy restored HIF‐1α levels and improved wound healing.…”

Association between Plasma Cellular Hypoxia and Mitochondrial Dysfunction Biomarkers and Disease Risk and Prognostic Factors in Type 2 Diabetic Saudi Patients

“…The utility of plasma HIF-1α as a systemic cellular hypoxia biomarker in different clinical settings was previously confirmed (18). However, a few discrepant studies ascribed it in diabetes and other diseases (19)(20)(21)(22). It is well established that diabetes is characterized by defective angiogenesis, vasculopathy and poor wound-healing partly due to relative tissue hypoxia and reduced autophagy.…”

“…Homeostatic model assessment of IR showed positive correlation versus each of age, ABSI, BMI, AIP and CRP (particularly in controls) but negative correlation Serum HIF-1α increases and negatively correlates survival in non-diabetic patients with acute decompensated heart failure (20). Moreover, serum level of HIF-1α in T2DM patients is significantly higher than that in healthy controls and correlates with kidney function and disease duration (22). Specific allelic polymorphism in HIF-1α gene prevails in diabetic patients and complicated diabetes than healthy controls leading to a pathogenetic decrease in HIF-1α messenger ribonucleic acid expression irrespective of the oxygen conditions of cells (24).…”