Serum levels of mac-2 binding protein are associated with diabetic microangiopathy and macroangiopathy in people with type 2 diabetes.

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. 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) . 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). 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.

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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.