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Background <p>Prediabetes is a well-established risk factor for cardiovascular diseases (CVD), stroke, and cancer, but whether this risk is uniform across all individuals remains uncertain. Additionally, heterogeneity within the prediabetic population, driven by mechanisms like lipid metabolism dysfunction and inflammation, has not been fully explored.</p> Methods <p>This study analyzed data from 3,065 prediabetic participants (mean age: 58.8 ± 9.7, 53.8% women) from the China Health and Retirement Longitudinal Study. We used generalized linear models, Cox regression, and subgroup analyses to evaluate the risk of progression to CVD, stroke, and cancer. To delineate distinct subgroups among individuals with prediabetes, we devised a stratification framework predicated on the coexistence of dyslipidemia, the triglyceride-glucose (TyG) index, and the C-reactive protein-triglyceride glucose (CTI) index.</p> Results <p>Prediabetic participants were classified into four subgroups: metabolically sensitive, inflammation-driven, metabolic lipotoxicity, and systemic metabolic-inflammatory (a subtype defined by concurrent dyslipidemia and elevated CTI values indicating combined metabolic and inflammatory dysregulation). Compared with the metabolically sensitive subtype, the inflammation-driven, metabolic lipotoxicity, and systemic metabolic-inflammatory subtypes exhibited significantly heightened risks of cancer, CVD, and stroke, even after adjustment for confounding variables (all <i>p</i> &lt; 0.05). Furthermore, dose–response analyses revealed a robust linear association between increasing levels of CTI, low-density lipoprotein cholesterol, and TyG index and the incidence of cancer, CVD, and stroke.</p> Conclusions <p>Prediabetic individuals with inflammation and/or lipid metabolism dysregulation are at a markedly higher risk of developing CVD, stroke, and cancer. Tailored prevention and intervention strategies are necessary to address the distinct risk profiles within the prediabetic population.</p>

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Lipid metabolism–inflammation crosstalk and risk of incident cancer, cardiovascular diseases, and stroke among individuals with prediabetes: findings from a nationwide, population based, prospective cohort study

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年1月5日

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  • Wenjie Li,
  • Jian Chen,
  • Yiming Fu,
  • Wei Wang,
  • Qin Zeng

摘要

Background

Prediabetes is a well-established risk factor for cardiovascular diseases (CVD), stroke, and cancer, but whether this risk is uniform across all individuals remains uncertain. Additionally, heterogeneity within the prediabetic population, driven by mechanisms like lipid metabolism dysfunction and inflammation, has not been fully explored.

Methods

This study analyzed data from 3,065 prediabetic participants (mean age: 58.8 ± 9.7, 53.8% women) from the China Health and Retirement Longitudinal Study. We used generalized linear models, Cox regression, and subgroup analyses to evaluate the risk of progression to CVD, stroke, and cancer. To delineate distinct subgroups among individuals with prediabetes, we devised a stratification framework predicated on the coexistence of dyslipidemia, the triglyceride-glucose (TyG) index, and the C-reactive protein-triglyceride glucose (CTI) index.

Results

Prediabetic participants were classified into four subgroups: metabolically sensitive, inflammation-driven, metabolic lipotoxicity, and systemic metabolic-inflammatory (a subtype defined by concurrent dyslipidemia and elevated CTI values indicating combined metabolic and inflammatory dysregulation). Compared with the metabolically sensitive subtype, the inflammation-driven, metabolic lipotoxicity, and systemic metabolic-inflammatory subtypes exhibited significantly heightened risks of cancer, CVD, and stroke, even after adjustment for confounding variables (all p < 0.05). Furthermore, dose–response analyses revealed a robust linear association between increasing levels of CTI, low-density lipoprotein cholesterol, and TyG index and the incidence of cancer, CVD, and stroke.

Conclusions

Prediabetic individuals with inflammation and/or lipid metabolism dysregulation are at a markedly higher risk of developing CVD, stroke, and cancer. Tailored prevention and intervention strategies are necessary to address the distinct risk profiles within the prediabetic population.