Association between circulating levels of 25-hydroxyvitamin d and metalloproteinase-10 (mmp 10) in patients with type 2 diabetes mellitus. cross-sectional study

Abstract BACKGROUND AND AIMS Matrix metalloproteinases (MMP) play an important role in diabetic kidney disease (DKD) (1). MMP-10 levels have been shown to increase progressively starting from the early stages of DKD (2). Vitamin D (vitD) deficit is associated with a higher risk of microangiopathy in diabetes. In humans, vitD status correlates inversely with MMP-9 circulating levels and VitD supplementation is associated with a decrease in these levels (3). In vitro, studies demonstrated reduced expression of MMP-10 after an exposure to vitD (4). However, no studies have yet assessed how vitD status is related to MMP-10 circulating levels. We aimed (1) to evaluate the association between the serum levels of 25-hydroxyvitamin D [25(OH)D3] and MMP-10 in a cohort of type 2 diabetes (T2D) patients and (2) to study a potential effect of chronic kidney disease (CKD) stage or estimated glomerular filtration rate (eGFRcr) on this association. METHOD The cross-sectional association between MMP-10 and 25(OH)D3 levels (>30 ng/mL, normal; 20–30 ng/mL, insufficiency; <20 ng/mL, deficiency; and relevant cut-offs 45 and 15 ng/mL) was investigated, by multivariate linear regression analysis after MMP-10 logarithm transformation, in 256 T2D patients recruited (2009–2016) in the Clinica Universidad de Navarra (Spain). Study protocol was approved by the Ethical Committee (2021.183TFG). Covariates were smoking habit, body adiposity percentage estimated by CUN-BAE formula, CKD stage and vitD3 supplement use. Age and sex were already included in the CKD-EPI formula. Interactions and collinearities were also analysed. Statistical analysis was performed using STATA software and two-tailed P-values <0.05 were considered statistically significant. RESULTS Characteristics of patients are given in Table 1. VitD deficit was significantly (P <0.001) more prevalent in patients with CKD (61%) compared with those without CKD (40%). MMP-10 showed a significant negative correlation with 25(OH)D3 (rho = –0.246; P <0.001), which remained significant including only CKD patients (rho = –0.283; P <0.001) and stronger above 45 ng/mL (rho = –0.7308, P <0.001) or moderate between 30 and 45 ng/mL (rho = –0.3290, P = 0.0045) (Fig. 1). In the fully adjusted model, MMP-10 was negatively associated (P = 0.019) with severe vitD deficiency [estimated coefficient –0.86 (–0.76 to –0.97)]. There was no interaction between covariates and 25(OH)D levels and collinearities were also discarded. CONCLUSION In T2D patients, circulating MMP-10 was inversely associated with serum 25(OH)D3 levels, especially in those patients with CKD and at the extremes of vitD level range. These results suggest that higher values of 25(OH)D3 should be targeted in these patients. The efficacy of vitD supplementation in reducing circulating MMP-10 levels should be further examined.