Background: Cholesterol uptake capacity (CUC) is a novel index of the functionality of serum high-density lipoprotein (HDL), which has been reported to be associated with insulin resistance and the cardiovascular risk. However, only a few studies investigated the association of CUC with the development of diabetes. Herein, we assessed the association of CUC with incident type 2 diabetes in a general Japanese population.

Methods: A total of 2,162 subjects aged 40-79 years without diabetes underwent comprehensive health examination including 75g OGTT and were followed-up prospectively for a median of 6.0 years. The amount of HDL-contained cholesterol per apolipoprotein A1 levels after incubating the participants’ HDL with cholesterol as CUC were measured at baseline. CUC levels were categorized into quartiles (Q1:<0.303, Q2:0.303-0.325, Q3:0.326-0.351, Q4:≥0.352 a.u.). The hazard ratios (HRs) and their 95% confidence intervals (CIs) of CUC levels on the incident diabetes were estimated by using a Cox’s proportional hazard model with adjustment for confounding factors.

Results: During the follow-up period, 219 subjects experienced diabetes. The multivariable-adjusted HR (95% CI) was significantly decreased with elevating levels of CUC: 1.00 (reference) in Q1, 0.83 (0.57, 1.20) in Q2, 0.77 (0.52, 1.14) in Q3 and 0.64 (0.42, 0.98) in Q4 (p=0.04 for trend). In the analysis combined serum HDL cholesterol level (≤50mg/dl [25 percentile value] vs. >51 mg/dl) and CUC (Q1-Q3 vs. Q4), HRs (95% CIs) for the incident diabetes compared to both low group were 0.72 (0.36, 1.45) in isolated high CUC group, 0.73 (0.50, 1.06) in isolated high HDL cholesterol group, and 0.56 (0.34, 0.93) in both high group (p=0.88 for interaction).

Conclusion: Our findings suggest that the risk of diabetes decreased with elevating CUC levels independent of HDL cholesterol levels in the general Japanese population.


Y. Hirakawa: None. R. Toh: Other Relationship; Self; Sysmex Corporation. M. Higashioka: None. M. Yoshinari: None. T. Honda: None. D. Yoshida: None. J. Hata: None. U. Nakamura: None. T. Kitazono: 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.


Japan Ministry of Education, Culture, Sports, Science and Technology; Japan Ministry of Health, Labour and Welfare; Japan Agency for Medical Research and Development

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