Background: Serum Mac-2 binding protein glycosylation isomer (M2BPGi) is a novel biomarker of chronic liver disease including liver fibrosis. Chronic liver disease has been acknowledged to cause glucose intolerance. However, few studies have addressed the association between serum M2BPGi levels and the risk of type 2 diabetes (T2D).

Methods: A total of 2,143 participants aged 40-79 years without diabetes were followed-up for a median of 7.0 years. Serum M2BPGi levels were measured at baseline and were categorized into quartiles: ≤ 0.40; 0.41-0.55; 0.56-0.75; and ≥0.76 (cut-off index). A Cox’s proportional hazards model was used to estimate hazard ratios (HRs) and their 95% CIs for the incident T2D with the adjustment for confounders-namely age, sex, family history of diabetes, systolic blood pressure, use of antihypertensive agents, serum total and HDL cholesterol, serum triglyceride, use of lipid-modifying agents, BMI, smoking, drinking, regular exercise, and fasting plasma glucose. The impact of serum M2BPGi levels on the predictive ability of incident T2D was evaluated with Harrell’s C statistics, continuous net reclassification improvement (cNRI), and integrated discrimination improvement (IDI).

Results: During follow-up periods, 219 subjects developed T2D. The multivariable-adjusted HR (95% CI) of developing T2D increased significantly with higher serum M2BPGi levels (p for trend=0.03), being 1.00 (reference) in Q1, 1.38 (0.89-2.15) in Q2, 1.51 (0.95-2.39) in Q3, 1.70 (1.07-2.70) in Q4. The predictive ability of incident T2D was improved by adding serum M2BPGi level to the model comprising aforementioned confounders: Harrell’s c-statistics from 0.787 to 0.795 (p=0.03), cNRI 0.19 (p=0.03), and IDI 0.004 (p=0.07).

Conclusion: Our findings suggest that higher serum M2BPGi level was a significant risk factor for T2D in the general Japanese population. Measuring serum M2BPGi level may be effective to detect the high-risk population of T2D.


M. Higashioka: None. Y. Hirakawa: None. M. Yoshinari: None. T. Honda: None. S. Sakata: None. M. Shibata: None. D. Yoshida: None. J. Hata: None. T. Kitazono: None. H. Osawa: None. T. Ninomiya: Research Support; Self; Asahi Kasei Corporation, Denka Company Limited, DeSC Healthcare, Inc, Mochida Pharmaceutical Co., Ltd., Suntory Beverage & Food Limited, Sysmex Corporation.

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