Impact of Plasma Xanthine Oxidoreductase Activity on the Mechanisms of Distal Symmetric Polyneuropathy Development in Patients with Type 2 Diabetes
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 (...
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MDPI AG
2021-08-01
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| author | Midori Fujishiro Hisamitsu Ishihara Katsuhiko Ogawa Takayo Murase Takashi Nakamura Kentaro Watanabe Hideyuki Sakoda Hiraku Ono Takeshi Yamamotoya Yusuke Nakatsu Tomoichiro Asano Akifumi Kushiyama |
| author_facet | Midori Fujishiro Hisamitsu Ishihara Katsuhiko Ogawa Takayo Murase Takashi Nakamura Kentaro Watanabe Hideyuki Sakoda Hiraku Ono Takeshi Yamamotoya Yusuke Nakatsu Tomoichiro Asano Akifumi Kushiyama |
| author_sort | Midori Fujishiro |
| collection | DOAJ |
| description | 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<sup>2</sup>, 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. |
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| last_indexed | 2024-03-10T08:59:02Z |
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| series | Biomedicines |
| spelling | doaj.art-0214beb415ce4845990878503464d78e2023-11-22T06:53:56ZengMDPI AGBiomedicines2227-90592021-08-0198105210.3390/biomedicines9081052Impact of Plasma Xanthine Oxidoreductase Activity on the Mechanisms of Distal Symmetric Polyneuropathy Development in Patients with Type 2 DiabetesMidori Fujishiro0Hisamitsu Ishihara1Katsuhiko Ogawa2Takayo Murase3Takashi Nakamura4Kentaro Watanabe5Hideyuki Sakoda6Hiraku Ono7Takeshi Yamamotoya8Yusuke Nakatsu9Tomoichiro Asano10Akifumi Kushiyama11Division of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, JapanDivision of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, JapanDepartment of Internal Medicine, Nihon University Hospital, 1-6 Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8309, JapanRadioisotope and Chemical Analysis Center, Pharmaceuticals Research Laboratories, Sanwa Kagaku Kenkyusho Co., Ltd., 363 Shiosaki, Hokusei-cho, Inabe-shi 511-0406, Mie, JapanMedical Affairs Department, Sanwa Kagaku Kenkyusho Co., Ltd., 35 Higashisotobori-cho, Higashi-ku, Nagoya 461-8631, Aichi, JapanDivision of Diabetes and Metabolic Diseases, Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Kami-cho, Itabashi-ku, Tokyo 173-8610, JapanDivision of Neurology, Respirology, Endocrinology and Metabolism, Department of Internal Medicine, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake 889-1692, Miyazaki, JapanDepartment of Clinical Cell Biology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Chiba, JapanDepartment of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Hiroshima, JapanDepartment of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Hiroshima, JapanDepartment of Medical Science, Graduate School of Medicine, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Hiroshima, JapanDepartment of Pharmacotherapy, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose 204-8588, Tokyo, JapanTo 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<sup>2</sup>, 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.https://www.mdpi.com/2227-9059/9/8/1052type 2 diabetesxanthine oxidoreductasedistal symmetric polyneuropathy |
| spellingShingle | Midori Fujishiro Hisamitsu Ishihara Katsuhiko Ogawa Takayo Murase Takashi Nakamura Kentaro Watanabe Hideyuki Sakoda Hiraku Ono Takeshi Yamamotoya Yusuke Nakatsu Tomoichiro Asano Akifumi Kushiyama Impact of Plasma Xanthine Oxidoreductase Activity on the Mechanisms of Distal Symmetric Polyneuropathy Development in Patients with Type 2 Diabetes Biomedicines type 2 diabetes xanthine oxidoreductase distal symmetric polyneuropathy |
| title | Impact of Plasma Xanthine Oxidoreductase Activity on the Mechanisms of Distal Symmetric Polyneuropathy Development in Patients with Type 2 Diabetes |
| title_full | Impact of Plasma Xanthine Oxidoreductase Activity on the Mechanisms of Distal Symmetric Polyneuropathy Development in Patients with Type 2 Diabetes |
| title_fullStr | Impact of Plasma Xanthine Oxidoreductase Activity on the Mechanisms of Distal Symmetric Polyneuropathy Development in Patients with Type 2 Diabetes |
| title_full_unstemmed | Impact of Plasma Xanthine Oxidoreductase Activity on the Mechanisms of Distal Symmetric Polyneuropathy Development in Patients with Type 2 Diabetes |
| title_short | Impact of Plasma Xanthine Oxidoreductase Activity on the Mechanisms of Distal Symmetric Polyneuropathy Development in Patients with Type 2 Diabetes |
| title_sort | impact of plasma xanthine oxidoreductase activity on the mechanisms of distal symmetric polyneuropathy development in patients with type 2 diabetes |
| topic | type 2 diabetes xanthine oxidoreductase distal symmetric polyneuropathy |
| url | https://www.mdpi.com/2227-9059/9/8/1052 |
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