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Comparative prognostic value of hemoglobin glycation index and glycation gap for mortality risk in adults: A

Xiaoying Sun1, Ping Yu1, Chun Zhang2

  • 1Department of Endocrinology, Huzhou Third Municipal Hospital, The Affiliated Hospital of Huzhou University, Huzhou, China.

Diabetes & Vascular Disease Research
|December 11, 2025
PubMed

Insights

The hemoglobin glycation index (HGI) and glycation gap (GG) can help predict mortality risk. Combined assessment of HGI and GG aids in identifying individuals at higher risk for cardiovascular disease (CVD) and all-cause mortality.

Area of Science:

  • Endocrinology
  • Cardiovascular Medicine
  • Epidemiology

Background:

  • Hemoglobin A1c (HbA1c) is a standard diabetes marker, but individual glycation levels vary.
  • Hemoglobin glycation index (HGI) and glycation gap (GG) quantify this discordance.
  • These markers may offer insights beyond HbA1c alone.

Purpose of the Study:

  • To compare the predictive capabilities of HGI and GG for all-cause and cardiovascular disease (CVD) mortality.
  • To assess the utility of HGI and GG in a nationally representative adult population.
  • To evaluate the combined predictive value of HGI and GG.

Main Methods:

  • Utilized data from 3468 adults in the US National Health and Nutrition Examination Survey (1999-2004).
  • Stratified participants based on median absolute values of HGI and GG.
  • Employed Cox proportional hazard models and time-dependent receiver-operating characteristic (ROC) curves to analyze associations with mortality.

Main Results:

  • Over a median follow-up of 101 months, 733 (12.48%) deaths occurred, including 210 from CVD.
  • The HGI+/GG+ group showed significantly higher hazard ratios for all-cause (1.36) and CVD mortality (1.91) compared to the HGI-/GG- group.
  • Both HGI and GG demonstrated comparable predictive accuracy (AUC 0.50-0.60) with a linear relationship to mortality risk.

Conclusions:

  • HGI and GG are valuable markers for predicting mortality risk, particularly CVD mortality.
  • Combined assessment of HGI and GG enhances risk stratification and identification of high-risk individuals.
  • These glycation markers provide additional prognostic information beyond standard HbA1c measurements.

Keywords:
NHANESall-cause mortalityglycation gaphemoglobin glycation indexreceiver-operating characteristic curve

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