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Background and aims <p>Recent studies have suggested an interplay between conicity index (C-index)-related diabetes risk and lipid burden. It is plausible that the atherogenic index of plasma (AIP), fatty liver, and HbA1c mediate the association between C-index and diabetes risk, though this has not been fully explored. This study explored whether AIP, fatty liver, and HbA1c mediate the relationship between C-index and diabetes risk, as well as their combined effect.</p> Methods <p>Data from 15,453 participants in the NAGALA Cohort were analyzed (median follow-up 5.39 years). Restricted Cubic Spline (RCS) and univariate Cox regression models adjusted for risk factors were used to assess the role of AIP in modifying the C-index-diabetes relationship. Mediation analysis assessed the contributing factors, and predictive models for diabetes were established.</p> Results <p>Among normoglycemic individuals, the AIP and C-index remained significantly and positively associated with diabetes risk. Higher AIP levels strengthened the C-index-diabetes association, particularly in the AIP range of 0.11-≤1.21. In the initial model, hazard ratios (HRs) for those in the fourth quartile of the C-index distribution in this group showed a significant HR of 2.22 (1.37–3.59). As fatty liver and HbA1c levels were progressively adjusted, the HRs gradually decreased, but a significant HR of 1.70 (1.05–2.76) was retained in the fully adjusted model. No significant association was observed in the other AIP strata. Furthermore, AIP, fatty liver, and HbA1c mediated the relationship between C-index and diabetes risk, with mediation effects of 9.8%, 25.0%, and 13.4%, respectively. Notably, the combined model incorporating AIP, fatty liver, HbA1c, and the C-index achieved the highest predictive performance (AUC = 0.86), outperforming the C-index alone (AUC = 0.68).</p> Conclusions <p>C-index was significantly associated with diabetes risk, modified by AIP, fatty liver, and HbA1c. These findings emphas ize the importance of AIP along with the C-index, particularly in the context of fatty liver and HbA1c, for diabetes risk screening and management.</p>

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AIP, fatty liver, and HbA1c as modifiers of the C-index and diabetes risk relationship

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月2日

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  • Yanmei Liu,
  • Rui Shi,
  • Huiying Cao,
  • Jian Zhang,
  • Shuangyue Li,
  • Xilin Kang,
  • Yongjuan Ma,
  • Yudian Wu,
  • Yangfan Guo,
  • Lei Feng

摘要

Background and aims

Recent studies have suggested an interplay between conicity index (C-index)-related diabetes risk and lipid burden. It is plausible that the atherogenic index of plasma (AIP), fatty liver, and HbA1c mediate the association between C-index and diabetes risk, though this has not been fully explored. This study explored whether AIP, fatty liver, and HbA1c mediate the relationship between C-index and diabetes risk, as well as their combined effect.

Methods

Data from 15,453 participants in the NAGALA Cohort were analyzed (median follow-up 5.39 years). Restricted Cubic Spline (RCS) and univariate Cox regression models adjusted for risk factors were used to assess the role of AIP in modifying the C-index-diabetes relationship. Mediation analysis assessed the contributing factors, and predictive models for diabetes were established.

Results

Among normoglycemic individuals, the AIP and C-index remained significantly and positively associated with diabetes risk. Higher AIP levels strengthened the C-index-diabetes association, particularly in the AIP range of 0.11-≤1.21. In the initial model, hazard ratios (HRs) for those in the fourth quartile of the C-index distribution in this group showed a significant HR of 2.22 (1.37–3.59). As fatty liver and HbA1c levels were progressively adjusted, the HRs gradually decreased, but a significant HR of 1.70 (1.05–2.76) was retained in the fully adjusted model. No significant association was observed in the other AIP strata. Furthermore, AIP, fatty liver, and HbA1c mediated the relationship between C-index and diabetes risk, with mediation effects of 9.8%, 25.0%, and 13.4%, respectively. Notably, the combined model incorporating AIP, fatty liver, HbA1c, and the C-index achieved the highest predictive performance (AUC = 0.86), outperforming the C-index alone (AUC = 0.68).

Conclusions

C-index was significantly associated with diabetes risk, modified by AIP, fatty liver, and HbA1c. These findings emphas ize the importance of AIP along with the C-index, particularly in the context of fatty liver and HbA1c, for diabetes risk screening and management.