What is the clinical evidence from this study?

Study design: Cohort. Population: Peripheral artery disease (n=456743). Intervention: Estimated glucose disposal rate (eGDR) vs. Lowest eGDR quartile (Q1). Primary outcome: Incident peripheral artery disease (HR 0.67, 95% CI 0.63-0.72, p=<0.001).

What does this research mean for the field?

Higher estimated glucose disposal rate (eGDR), a surrogate marker for insulin resistance, is non-linearly associated with a significantly reduced risk of developing peripheral artery disease. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This study aims to assess the relationship between estimated glucose disposal rate and the risk of peripheral artery disease.

June 6, 2026Open Access

Associations between estimated glucose disposal rate and peripheral artery disease: evidence from the UK Biobank and NHANES

Q: What are the key findings of this study?

Participants in the highest estimated glucose disposal rate quartile had a significantly lower risk of developing peripheral artery disease compared to those in the lowest quartile (HR 0.67).

Q: What does this research mean for the field?

Higher estimated glucose disposal rate (eGDR), a surrogate marker for insulin resistance, is non-linearly associated with a significantly reduced risk of developing peripheral artery disease. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

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

This study aims to assess the relationship between estimated glucose disposal rate and the risk of peripheral artery disease.

Key Result

Participants in the highest estimated glucose disposal rate quartile had a significantly lower risk of developing peripheral artery disease compared to those in the lowest quartile (HR 0.67).

Key Points

This study aims to assess the relationship between estimated glucose disposal rate and the risk of peripheral artery disease.
Included 456,743 participants free of PAD from the UK Biobank cohort
Conducted cross-sectional analysis on 7,208 NHANES participants
Utilized multivariable Cox regression analysis for associations.
Participants in the highest eGDR quartile (Q4) showed a reduced PAD risk (HR = 0.67, 95% CI: 0.63-0.72, P < 0.001)
Nonlinear inverse relationship found between eGDR and PAD risk, with an inflection point at 7.829 (P < 0.001)
Similar association observed between eGDR and prevalent PAD in NHANES.

Study Design

Type

Cohort (n=456,743)

Multicenter

Yes

Structured PICO

Is higher estimated glucose disposal rate (eGDR) associated with a reduced risk of incident peripheral artery disease (PAD) in the general population?

Population

456,743 adults aged 37 to 73 years free of peripheral artery disease at baseline from the UK Biobank, followed for a median of 13.8 years.

Exposure

Highest estimated glucose disposal rate (eGDR) quartile (Q4)

Comparator

Lowest estimated glucose disposal rate (eGDR) quartile (Q1)

Outcome

Incident peripheral artery disease (PAD)hard clinical

Higher estimated glucose disposal rate, a surrogate marker of insulin resistance, is nonlinearly associated with a lower risk of developing peripheral artery disease.

Main Result

Hazard Ratio: 0.67 (95% CI 0.63–0.72)

p-value: p=<0.001

Limitations

Observational study design cannot establish a causal relationship and residual confounding cannot be fully excluded.
eGDR serves as an indirect estimate of glucose utilization, lacking the precision of gold-standard methods like the hyperinsulinemic-euglycemic clamp.
eGDR was assessed from a single baseline measurement, limiting the ability to account for changes in insulin resistance over time.
Differences in study design and PAD definition between NHANES and the UK Biobank limited the direct comparability of the two analyses.

Abstract

BACKGROUND: Insulin resistance (IR) is considered a key pathogenic mechanism of peripheral artery disease (PAD). The estimated glucose disposal rate (eGDR) serves as a practical surrogate marker of IR. The study aimed to investigate the association between eGDR and incident PAD risk in the general population. METHODS: A total of 456,743 participants free of PAD at baseline were included from the prospective UK Biobank cohort. In addition, we examined the cross-sectional association between eGDR and prevalent PAD among 7,208 participants from the National Health and Nutrition Examination Survey (NHANES) as a supplementary analysis. RESULTS: Multivariable Cox regression analysis showed that participants in the highest eGDR quartile (Q4) experienced the greatest reduction in the risk of developing PAD compared with the reference group Q4 vs. Q1; fully adjusted hazard ratio (HR) = 0.67, 95% confidence interval (CI): 0.63-0.72, P < 0.001. Restricted cubic spline (RCS) curve and threshold effect analysis also suggested a significant nonlinear inverse relationship between eGDR and PAD risk, with an inflection point at 7.829 (P for overall < 0.001; P for nonlinearity < 0.001). Two-piecewise Cox regression further indicated that below the threshold, an increase in eGDR was associated with a greater reduction in PAD risk (HR = 0.85, 95% CI: 0.84-0.87, P < 0.001). A similar inverse association between eGDR and prevalent PAD was observed in the NHANES analysis. CONCLUSIONS: eGDR was inversely associated with PAD. Further studies are needed to explore the clinical utility of this association.

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