Nonlinear association of cholesterol, high-density lipoprotein, and glucose index with the risk of prediabetes and diabetes in normal-weight middle-aged and older Chinese adults: a multicenter retrospective cohort study

Q: What are the key findings of this study?

Higher CHG index was nonlinearly associated with increased incident prediabetes and diabetes (adjusted HR 2.20, 95% CI 1.90–2.54; p<0.0001), with a steep risk increase below the 5.07 inflection point.

Q: What is the clinical evidence from this study?

Study design: Cohort. Population: Normal-weight middle-aged and older adults without baseline prediabetes or diabetes (n=19981). Intervention: Cholesterol, high-density lipoprotein, and glucose (CHG) index vs. Lower CHG index levels (Quartile 1: 3.98–4.85). Primary outcome: Incident prediabetes and diabetes (fasting glucose ≥5.6 mmol/L or self-reported diagnosed diabetes during follow-up) (HR 2.20, 95% CI 1.90-2.54, p=<0.0001).

Q: What does this research mean for the field?

A higher cholesterol, high-density lipoprotein, and glucose (CHG) index is nonlinearly associated with an increased risk of incident prediabetes and diabetes in normal-weight middle-aged and older Chinese adults, with a sharp risk elevation occurring below an inflection point of 5.07. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To examine the relationship between the cholesterol, high-density lipoprotein, and glucose (CHG) index and incident prediabetes and diabetes in normal-weight middle-aged and older Chinese adults.

Junling Ding; Zhimao Cai; Xiang Wang; Lifen Qin; Weifeng Chen

doi:10.3389/fnut.2026.1949954

October 19, 2026Frontiers in NutritionOpen Access

Nonlinear association of cholesterol, high-density lipoprotein, and glucose index with the risk of prediabetes and diabetes in normal-weight middle-aged and older Chinese adults: a multicenter retrospective cohort study

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Key result

Higher CHG index linked to ~2.2-fold higher risk of incident prediabetes and diabetes.

HR 2.20
95% CI 1.90-2.54
P<0.0001
n=19,981

Why the study?

The relationship between the cholesterol, high-density lipoprotein, and glucose (CHG) index and dysglycemia is recognized in the general population, but it has been much less examined among normal-weight, middle-aged and older adults.

Does a higher cholesterol, high-density lipoprotein, and glucose (CHG) index increase the risk of incident prediabetes and diabetes in normal-weight middle-aged and older Chinese adults?

Key Points

To examine the relationship between the cholesterol, high-density lipoprotein, and glucose (CHG) index and incident prediabetes and diabetes in normal-weight middle-aged and older Chinese adults.
Multicenter retrospective cohort study of 19,981 Chinese adults (age ≥45 years, BMI 18.5–23.9 kg/m²) without baseline prediabetes or diabetes, followed for an average of 3.19 years (2010–2016).
Calculated the CHG index as Ln[(TC × FPG)/(2 × HDLC)] (mg/dL) and defined the primary composite outcome as fasting glucose ≥5.6 mmol/L or self-reported diagnosed diabetes.
Used multivariable Cox proportional hazards regression, smoothed curve fitting, and two-piecewise regression models.
Higher CHG index was independently linked to the primary outcome (fully adjusted continuous HR: 2.20, 95% CI: 1.90–2.54, p < 0.0001; Quartile 4 vs Quartile 1 HR: 1.91, 95% CI: 1.69–2.16, p < 0.0001).
Smoothed curve fitting revealed a significant nonlinear association (inflection point 5.07, p < 0.001); risk increased below 5.07 (HR: 6.39, 95% CI: 4.73–8.64, p < 0.0001) but showed no significant link above it (HR: 1.02, 95% CI: 0.79–1.31, p = 0.8740).
The association was significantly stronger in participants under age 60 (HR: 2.51 vs 1.65 for ≥60 years, p = 0.0054) and in females (HR: 2.65 vs 1.77 for males, p = 0.0011).

Study Design

Type

Cohort (n=19,981)

Multicenter

Yes

Structured PICO

Does a higher cholesterol, high-density lipoprotein, and glucose (CHG) index increase the risk of incident prediabetes and diabetes in normal-weight middle-aged and older Chinese adults?

P

Population

19,981 normal-weight (BMI 18.5–23.9 kg/m2) Chinese adults aged ≥45 years (mean age 55.73 years, 57.19% female) without prediabetes or diabetes at baseline, followed for a mean of 3.19 years.

E

Exposure

Cholesterol, high-density lipoprotein, and glucose (CHG) index, calculated as Ln[(TC × FPG)/(2 × HDL-C)] in mg/dL, evaluated as a continuous variable and across quartiles (Q2: 4.85–5.01, Q3: 5.01–5.18, Q4: 5.18–7.36).

C

Comparator

Lowest quartile of the CHG index (Q1: 3.98–4.85) or lower continuous CHG index values.

O

Outcome

Composite of incident prediabetes and diabetes (defined as fasting plasma glucose ≥5.6 mmol/L or self-reported diagnosed diabetes at follow-up examination) over a mean follow-up of 3.19 years.composite

Main Result

Hazard Ratio: 2.2 (95% CI 1.9–2.54)

p-value: p=<0.0001

The CHG index shows a strong nonlinear positive association with incident prediabetes and diabetes up to a threshold of 5.07 in normal-weight middle-aged and older Chinese adults, offering a low-cost tool to identify metabolically vulnerable lean individuals.

Limitations

Retrospective observational cohort design precludes establishing causality
Study population was exclusively Chinese, limiting generalizability to other ethnic groups or geographic regions
Potential residual confounding from unmeasured factors such as diet, physical activity, and socioeconomic status
Substantial missing data (>76%) for smoking and drinking status prevented their inclusion in adjusted models
Relatively short mean follow-up of 3.19 years may not capture long-term risk trajectories
Retrospective observational cohort study design cannot establish causality
Exclusively Chinese study population limits generalizability to other ethnic groups or regions
Potential residual confounding from unmeasured variables such as diet, physical activity, and socioeconomic status
High missing data rates (>76%) for smoking and drinking status precluded their inclusion in multivariable adjustment models
Mean follow-up duration of 3.19 years may not capture long-term risk trajectories

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Answers are grounded in this paper and cite their sources.

Implication

CHG index may flag prediabetes risk in normal-weight adults; extends general-population links but remains hypothesis-generating pending prospective validation.

Abstract

Background The relationship between the cholesterol, high-density lipoprotein, and glucose (CHG) index and dysglycemia is widely recognized in the general population; however, this relationship has been much less examined among normal-weight, middle-aged and older adults—a subgroup routinely marginalized in metabolic research. Accordingly, the current study was designed to evaluate the relationship of the CHG index with incident prediabetes and diabetes specifically among this population. Methods The study cohort comprised 19,981 Chinese adults (age ≥45 years, BMI 18.5–23.9 kg/m 2 ) without prediabetes or diabetes at baseline, sourced from a multicenter retrospective analysis of nationwide screening data (2010–2016). The CHG index was calculated as Ln[(TC × FPG)/(2 × HDLC)] (mg/dL). The primary outcome was incident- prediabetes and diabetes. To evaluate the association, we applied Cox proportional hazards models, along with smooth curve fitting and two-piecewise regression. Results During an average follow-up of 3.19 years, a higher CHG index was significantly linked to a greater risk of the outcome. After adjustment (Model 3), the hazard ratio (HR) for the CHG index as a continuous variable was 2.20 (95% CI: 1.90–2.54). Compared with Quartile 1, the HRs for Quartiles 2, 3, and 4 were 1.42, 1.86, and 1.91, respectively (all p < 0.0001). A significant nonlinear relationship was identified (log-likelihood ratio test, p < 0.001), with the inflection point located at a CHG index of 5.07. To the left of the inflection point, each unit increase in CHG index was associated with a 6.39-fold increase in risk (HR: 6.39, 95% CI: 4.73–8.64), while no significant link was observed to the right (HR: 1.02, 95% CI: 0.79–1.31). Conclusion This study indicates a nonlinear positive association between the CHG index and the risk of incident prediabetes and diabetes among normal-weight middle-aged and older Chinese adults. Future research employing large prospective cohorts is warranted to fully explicate the mechanisms and establish a causal nexus.

Discussion

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Cite This Study

Ding et al. (2026) conducted a cohort in Normal-weight middle-aged and older adults without baseline prediabetes or diabetes (n=19,981). Cholesterol, high-density lipoprotein, and glucose (CHG) index vs. Lower CHG index levels (Quartile 1: 3.98–4.85) was evaluated on Incident prediabetes and diabetes (fasting glucose ≥5.6 mmol/L or self-reported diagnosed diabetes during follow-up) (HR 2.20, 95% CI 1.90-2.54, p=<0.0001). Higher CHG index was nonlinearly associated with increased incident prediabetes and diabetes (adjusted HR 2.20, 95% CI 1.90–2.54; p<0.0001), with a steep risk increase below the 5.07 inflection point.

synapsesocial.com/papers/6aee6b8671a75948062209c3 https://doi.org/10.3389/fnut.2026.1949954

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Nonlinear association of cholesterol, high-density lipoprotein, and glucose index with the risk of prediabetes and diabetes in normal-weight middle-aged and older Chinese adults: a multicenter retrospective cohort study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Nonlinear association of cholesterol, high-density lipoprotein, and glucose index with the risk of prediabetes and diabetes in normal-weight middle-aged and older Chinese adults: a multicenter retrospective cohort study

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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