Glucose Variability is Independently Correlated with Serum Level of Pigment Epithelium-Derived Factor in Type 2 Diabetes

INTRODUCTION: Pigment epithelium-derived factor (PEDF) may play a role in cardiometabolic disorders. The aim of this study was to investigate which biochemical and clinical parameters are independently associated with serum PEDF levels in patients with type 2 diabetes mellitus (T2DM). METHODS: We performed a cross-sectional analysis of 124 patients with T2DM who underwent continuous glucose monitoring (CGM) and blood chemistry analysis, including the diacron-reactive oxygen metabolites (d-ROMs) test and serum PEDF measurement (study 1). Then we investigated whether the changes in the studied biochemical and clinical parameters after 24 weeks of treatment (Δparameters) with anti-hyperglycemic agents, including sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and/or insulin and anti-hypertensive drugs and statins, were independently correlated with change in PEDF (ΔPEDF) in 52 of the patients with T2DM for whom there was sufficient serum samples to perform the post-treatment analysis (study 2). Serum levels of PEDF were measured with an enzyme-linked immunosorbent assay. CGM metrics were calculated on days 2 and 3. Oxidative stress was evaluated using the d-ROMs test. RESULTS: Body mass index (BMI), triglycerides, fasting C-peptide, mean amplitude of glycemic excursions (MAGE), urinary albumin-to-creatinine ratio (UACR), and d-ROMs were positively associated with serum PEDF level, and high-density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) were inversely associated with serum PEDF level. Because these parameters were correlated with each other, multivariate stepwise analysis was performed: eGFR, HDL-C, BMI, MAGE, and UACR remained significant (R(2) = 0.452). Furthermore, ΔMAGE and Δd-ROMs were positively correlated with ΔPEDF in study 2. CONCLUSIONS: The results of this study suggest that MAGE may be independently correlated with elevations in serum PEDF level in patients with T2DM.