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Serum levels of mac-2 binding protein are associated with diabetic microangiopathy and macroangiopathy in people with type 2 diabetes
  1. Yoshitaka Hashimoto1,
  2. Masahide Hamaguchi1,
  3. Ayumi Kaji1,
  4. Ryosuke Sakai1,
  5. Noriyuki Kitagawa1,2,
  6. Michiaki Fukui1
  1. 1Department of Endocrinology and Metabolism, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan
  2. 2Department of Diabetology, Kameoka Municipal Hospital, Kameoka, Japan
  1. Correspondence to Dr Yoshitaka Hashimoto; y-hashi{at}koto.kpu-m.ac.jp

Abstract

Introduction Non-alcoholic fatty liver disease is reportedly associated with type 2 diabetes and progressive liver fibrosis, as evaluated by transient elastography, and has been linked with micro- and macroangiopathy in people with type 2 diabetes. The purpose of this cross-sectional study was to investigate the association between serum mac-2 binding protein glycosylation isomer (M2BPGi) levels and diabetic complications in people with type 2 diabetes.

Research design and methods Serum M2BPGi levels were measured in terms of cut-off index (C.O.I.) units. Urinary albumin excretion (UAE) was calculated and nephropathy was graded as normoalbuminuria, microalbuminuria, or macroalbuminuria. Retinopathy was divided into three groups: no-diabetic retinopathy (NoDR), non-proliferative-diabetic retinopathy (NPDR), or proliferative-diabetic retinopathy (PDR) .

Results The mean age for the 363 studied subjects (212 males) was 66.4±10.6 years, the median serum M2BPGi level was 0.77 (0.57–1.04) C.O.I., and the median UAE was 22 (9–82.1) mg/g creatinine. M2BPGi levels in microalbuminuria (0.83 (0.61 to 1.18) C.O.I.) and macroalbuminuria (0.88 (0.67 to 1.22) C.O.I.) cases were higher than those in normoalbuminuria cases (0.71 (0.54 to 0.92) C.O.I.). M2BPGi levels in NPDR (0.93 (0.68 to 1.28) C.O.I.) and PDR (0.95 (0.71 to 1.31) C.O.I.) cases were higher than in cases with NoDR (0.73 (0.56 to 0.99) C.O.I.). Furthermore, M2BPGi levels in subjects with a history of cardiovascular diseases were higher than in those with no such history (0.82 (0.65 to 1.22) vs 0.76 (0.55 to 1.03) C.O.I., p=0.019). The logarithm of (M2BPGi+1) was associated with the logarithm of UAE values after adjusting for covariates (standardized β=0.107, p=0.031).

Conclusions This study reveals a close association between serum M2BPGi levels and diabetic microangiopathy and macroangiopathy in people with type 2 diabetes. The results also show that liver fibrosis, evaluated by M2BPGi, is independently associated with an increased risk of albuminuria.

  • liver disease
  • cardiovacsular disease(s)
  • albuminuria
  • biomarkers
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Footnotes

  • Contributors YH designed the study, researched, analyzed and interpretation data, and wrote manuscript. MH designed the study, researched the data, and contributed to discussion. AK and RS researched and analyzed data and contributed to discussion. NK researched the data and contributed to discussion. MF designed the study, interpreted the data, and contributed to discussion. All authors approved the final version of the manuscript and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests YH received grant support from Asahi Kasei Pharma and honoraria from Mitsubishi Tanabe Pharma Corp and Novo Nordisk Pharma Ltd. MH received grant support from Asahi Kasei Pharma, payment for development of educational presentations from MSD K.K., Mitsubishi Tanabe Pharma Corp, Kowa Co. Ltd. and Sumitomo Dainippon Pharma Co. Ltd., and royalties from US 10,238,714 B2. MF received research supports and payment for development of educational presentation from AstraZeneca plc., Astellas Pharma Inc., Nippon Boehringer Ingelheim Co. Ltd., Daiichi Sankyo Co. Ltd., Eli Lilly Japan K.K., Kyowa Hakko Kirin Co. Ltd., Kissei Pharmaceutical Co. Ltd., MSD K.K., Sumitomo Dainippon Pharma Co. Ltd., Kowa Co. Ltd., Mitsubishi Tanabe Pharma Corp, Novo Nordisk Pharma Ltd., Sanwa Kagaku Kenkyusho Co. Ltd., Sanofi K.K., Ono Pharma Co. Ltd., Taisho Pharma Co. Ltd., Bayer Yakuhin, Ltd., Mochida Pharma Co. Ltd., Johnson & Johnson k.k. Medical Co., Nippon Chemiphar Co. Ltd., Terumo Corp, Teijin Pharma Ltd., and Takeda Pharma Co. Ltd.

  • Patient consent for publication Not required.

  • Ethics approval The Ethics Committee of Kyoto Prefectural University of Medicine permitted this study (No. RBMR-E-466–5).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data are available on reasonable request. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.