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

Tomoki Fujikawa; Makoto Ohara; Yo Kohata; Hiroe Nagaike; Ayako Fukase; Naoya Osaka; Hironori Yashima; Nobuko Sato; Hideki Kushima; Kyoko Shinmura; Yasuyoshi Takahashi; Munenori Hiromura; Michishige Terasaki; Yusaku Mori; Tomoyasu Fukui; Takanori Matsui; Tsutomu Hirano; Sho-Ichi Yamagishi

doi:10.1007/s13300-021-01008-y

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

Diabetes Ther. 2021 Mar;12(3):827-842. doi: 10.1007/s13300-021-01008-y. Epub 2021 Feb 13.

Authors

Tomoki Fujikawa¹, Makoto Ohara², Yo Kohata¹, Hiroe Nagaike¹, Ayako Fukase¹, Naoya Osaka¹, Hironori Yashima¹, Nobuko Sato¹, Hideki Kushima¹, Kyoko Shinmura¹, Yasuyoshi Takahashi¹, Munenori Hiromura¹, Michishige Terasaki¹, Yusaku Mori³, Tomoyasu Fukui¹, Takanori Matsui⁴, Tsutomu Hirano^{1

5}, Sho-Ichi Yamagishi¹

Affiliations

¹ Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
² Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan. s6018@nms.ac.jp.
³ Anti-Glycation Research Section, Division of Diabetes, Metabolism, and Endocrinology, Department of Medicine, Showa University School of Medicine, Tokyo, Japan.
⁴ Department of Pathophysiology and Therapeutics of Diabetic Vascular Complications, Kurume University School of Medicine, Kurume, Japan.
⁵ Diabetes Center, Ebina General Hospital, Ebina, Japan.

Abstract

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 (R² = 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.

Keywords: Cardiovascular disease; Continuous glucose monitoring; Glucose variability; Oxidative stress; Type 2 diabetes mellitus; pigment epithelium-derived factor.