PMID- 33586119 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210518 IS - 1869-6953 (Print) IS - 1869-6961 (Electronic) IS - 1869-6961 (Linking) VI - 12 IP - 3 DP - 2021 Mar TI - Glucose Variability is Independently Correlated with Serum Level of Pigment Epithelium-Derived Factor in Type 2 Diabetes. PG - 827-842 LID - 10.1007/s13300-021-01008-y [doi] AB - 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 (Deltaparameters) 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 (DeltaPEDF) 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, DeltaMAGE and Deltad-ROMs were positively correlated with DeltaPEDF 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. FAU - Fujikawa, Tomoki AU - Fujikawa T AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. FAU - Ohara, Makoto AU - Ohara M AUID- ORCID: 0000-0002-6137-5493 AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. s6018@nms.ac.jp. FAU - Kohata, Yo AU - Kohata Y AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. FAU - Nagaike, Hiroe AU - Nagaike H AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. FAU - Fukase, Ayako AU - Fukase A AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. FAU - Osaka, Naoya AU - Osaka N AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. FAU - Yashima, Hironori AU - Yashima H AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. FAU - Sato, Nobuko AU - Sato N AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. FAU - Kushima, Hideki AU - Kushima H AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. FAU - Shinmura, Kyoko AU - Shinmura K AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. FAU - Takahashi, Yasuyoshi AU - Takahashi Y AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. FAU - Hiromura, Munenori AU - Hiromura M AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. FAU - Terasaki, Michishige AU - Terasaki M AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. FAU - Mori, Yusaku AU - Mori Y AD - Anti-Glycation Research Section, Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. FAU - Fukui, Tomoyasu AU - Fukui T AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. FAU - Matsui, Takanori AU - Matsui T AD - Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan. FAU - Hirano, Tsutomu AU - Hirano T AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. AD - Diabetes Center, Ebina General Hospital, Ebina, Japan. FAU - Yamagishi, Sho-Ichi AU - Yamagishi SI AD - Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. LA - eng PT - Journal Article DEP - 20210213 PL - United States TA - Diabetes Ther JT - Diabetes therapy : research, treatment and education of diabetes and related disorders JID - 101539025 PMC - PMC7947132 OTO - NOTNLM OT - Cardiovascular disease OT - Continuous glucose monitoring OT - Glucose variability OT - Oxidative stress OT - Type 2 diabetes mellitus OT - pigment epithelium-derived factor EDAT- 2021/02/16 06:00 MHDA- 2021/02/16 06:01 PMCR- 2021/02/13 CRDT- 2021/02/15 06:15 PHST- 2020/12/12 00:00 [received] PHST- 2021/01/20 00:00 [accepted] PHST- 2021/02/16 06:00 [pubmed] PHST- 2021/02/16 06:01 [medline] PHST- 2021/02/15 06:15 [entrez] PHST- 2021/02/13 00:00 [pmc-release] AID - 10.1007/s13300-021-01008-y [pii] AID - 1008 [pii] AID - 10.1007/s13300-021-01008-y [doi] PST - ppublish SO - Diabetes Ther. 2021 Mar;12(3):827-842. doi: 10.1007/s13300-021-01008-y. Epub 2021 Feb 13.