PMID- 34440256 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20210830 IS - 2227-9059 (Print) IS - 2227-9059 (Electronic) IS - 2227-9059 (Linking) VI - 9 IP - 8 DP - 2021 Aug 19 TI - Impact of Plasma Xanthine Oxidoreductase Activity on the Mechanisms of Distal Symmetric Polyneuropathy Development in Patients with Type 2 Diabetes. LID - 10.3390/biomedicines9081052 [doi] LID - 1052 AB - To unravel associations between plasma xanthine oxidoreductase (XOR) and diabetic vascular complications, especially distal symmetric polyneuropathy (DSP), we investigated plasma XOR activities using a novel assay. Patients with type 2 diabetes mellitus (T2DM) with available nerve conduction study (NCS) data were analyzed. None were currently taking XOR inhibitors. XOR activity of fasting blood samples was assayed using a stable isotope-labeled substrate and LC-TQMS. JMP Clinical version 5.0. was used for analysis. We analyzed 54 patients. Mean age was 64.7 years, mean body mass index was 26.0 kg/m(2), and mean glycated hemoglobin was 9.4%. The logarithmically transformed plasma XOR activity (ln-XOR) correlated positively with hypoxanthine, xanthine, visceral fatty area, and liver dysfunction but negatively with HDL cholesterol. ln-XOR correlated negatively with diabetes duration and maximum intima-media thickness. Stepwise multiple regression analysis revealed ln-XOR to be among selected explanatory factors for various NCS parameters. Receiver operating characteristic curves showed the discriminatory power of ln-XOR. Principal component analysis revealed a negative relationship of ln-XOR with F-waves as well as positive relationships of ln-XOR with hepatic steatosis and obesity-related disorders. Taken together, our results show plasma XOR activity to be among potential disease status predictors in T2DM patients. Plasma XOR activity measurements might reliably detect pre-symptomatic DSP. FAU - Fujishiro, Midori AU - Fujishiro M AD - Division of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, Japan. AD - Department of Internal Medicine, Nihon University Hospital, 1-6 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8309, Japan. FAU - Ishihara, Hisamitsu AU - Ishihara H AUID- ORCID: 0000-0001-8922-6660 AD - Division of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, Japan. FAU - Ogawa, Katsuhiko AU - Ogawa K AD - Department of Internal Medicine, Nihon University Hospital, 1-6 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8309, Japan. AD - Division of Neurology, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, Japan. FAU - Murase, Takayo AU - Murase T AD - Radioisotope and Chemical Analysis Center, Pharmaceuticals Research Laboratories, Sanwa Kagaku Kenkyusho Co., Ltd., 363 Shiosaki, Hokusei-cho, Inabe-shi 511-0406, Mie, Japan. FAU - Nakamura, Takashi AU - Nakamura T AD - Medical Affairs Department, Sanwa Kagaku Kenkyusho Co., Ltd., 35 Higashisotobori-cho, Higashi-ku, Nagoya 461-8631, Aichi, Japan. FAU - Watanabe, Kentaro AU - Watanabe K AD - Division of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, Japan. FAU - Sakoda, Hideyuki AU - Sakoda H AD - Division of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake 889-1692, Miyazaki, Japan. FAU - Ono, Hiraku AU - Ono H AD - Department of Clinical Cell Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Chiba, Japan. FAU - Yamamotoya, Takeshi AU - Yamamotoya T AD - Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Hiroshima, Japan. FAU - Nakatsu, Yusuke AU - Nakatsu Y AD - Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Hiroshima, Japan. FAU - Asano, Tomoichiro AU - Asano T AD - Department of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Hiroshima, Japan. FAU - Kushiyama, Akifumi AU - Kushiyama A AUID- ORCID: 0000-0003-1385-7487 AD - Department of Pharmacotherapy, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose 204-8588, Tokyo, Japan. LA - eng PT - Journal Article DEP - 20210819 PL - Switzerland TA - Biomedicines JT - Biomedicines JID - 101691304 PMC - PMC8391363 OTO - NOTNLM OT - distal symmetric polyneuropathy OT - type 2 diabetes OT - xanthine oxidoreductase COIS- H.I. has served on the advisory board of Astellas Pharma, has received lecture fees from Astellas Pharma, MSD, Mitsubishi Tanabe Pharma, Nippon Boehringer Ingelheim, and Novartis Pharma, and has received grants from Ono Pharmaceutical, Nippon Boehringer Ingelheim, Sanofi, Mitsubishi Tanabe Pharma, Eli Lilly, Daiichi-Sankyo, Novo Nordisk Pharma and MSD. M.F., K.O., T.M., T.N., K.W., H.S., H.O., T.Y., Y.N., T.A., and A.K. have no conflict of interest regarding the contents of this article to declare. EDAT- 2021/08/28 06:00 MHDA- 2021/08/28 06:01 PMCR- 2021/08/19 CRDT- 2021/08/27 01:06 PHST- 2021/06/30 00:00 [received] PHST- 2021/08/14 00:00 [revised] PHST- 2021/08/16 00:00 [accepted] PHST- 2021/08/27 01:06 [entrez] PHST- 2021/08/28 06:00 [pubmed] PHST- 2021/08/28 06:01 [medline] PHST- 2021/08/19 00:00 [pmc-release] AID - biomedicines9081052 [pii] AID - biomedicines-09-01052 [pii] AID - 10.3390/biomedicines9081052 [doi] PST - epublish SO - Biomedicines. 2021 Aug 19;9(8):1052. doi: 10.3390/biomedicines9081052.