What is the clinical evidence from this study?

Study design: Cohort. Population: Prediabetes (n=14568). Intervention: Prediabetes subtypes vs. Overweight and normotensive group. Primary outcome: Mortality.

What does this research mean for the field?

Prediabetes subtypes exhibit heterogeneous mortality risks, with insulin-resistant subtypes—specifically obesity with severe insulin resistance and older age with severe insulin resistance—associated with the highest mortality rates in a nationally representative sample, although these differences were not observed in pooled cohort studies. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This work aims to identify prediabetes subtypes associated with mortality risk to enhance preventive measures.

June 7, 2026

2318-P: Heterogeneity in Rates of Mortality among Subtypes of Prediabetes

Key Result

Insulin-resistant prediabetes subtypes were associated with higher rates of mortality compared to overweight and normotensive groups in the NHANES validation sample, but not in the pooled cohorts.

Key Points

This work aims to identify prediabetes subtypes associated with mortality risk to enhance preventive measures.
Analyzed data from 14,568 adults with prediabetes over 15 years;
Classified subtypes using clustering of ten variables;
Utilized Cox proportional hazards for hazard ratio estimations.
2,198 participants died in the analytic sample;
Insulin-resistant subtypes showed higher mortality risk, particularly in validation among NHANES cases.
No significant differences observed in 15-year hazards across the seven prediabetes subtypes in the pooled cohorts.

Study Design

Type

Cohort (n=14,568)

Multicenter

Yes

Structured PICO

Do different subtypes of prediabetes have different rates of mortality?

Population

14,568 adults with prediabetes from pooled cohort studies, followed for up to 15 years for mortality.

Exposure

Classification into seven prediabetes subtypes using data-driven clustering of ten variables

Comparator

Comparison among different prediabetes subtypes (e.g., relative to overweight and normotensive group)

Outcome

Mortality at 15 yearshard clinical

Insulin-resistant subtypes of prediabetes may be associated with higher mortality risk, though results vary by cohort, highlighting the need for further risk stratification.

Abstract

Introduction and Objective: Prediabetes is a clinically heterogeneous and an independent risk factor for mortality. Identifying subtypes of prediabetes at elevated risk for mortality can improve targeted enrollment in preventive interventions. Methods: Adults (≥18 years; n = 14,568) with prediabetes (HbA1c 5.6-6.4% or fasting glucose 100-125 mg/dL) from pooled cohort studies were followed until death or administrative censoring at 15 years. Prediabetes was classified into seven subtypes using data-driven clustering of ten variables (Panel A). Cox proportional hazards was used to estimate covariate-adjusted relative hazards (HR) by subtype. Validation was conducted among prediabetes cases in the nationally representative NHANES 1999-2018 sample with linked mortality data (n = 11,284). Results: Among the analytic sample (57 years SD: 10; 51% female), 2,198 died. Prediabetes subtypes were similar in their 15-year hazards of mortality. In the validation sample (52 years SD: 18.1; 46% female), relative to the overweight and normotensive group, obesity with severe insulin resistance and older age with severe insulin resistance were associated with highest rates of mortality. Conclusion: Prediabetes subtypes may differ in mortality risk, with higher hazard ratios observed among insulin-resistant (IR) subtypes in NHANES but not in the Pooled Cohorts. Further research should disentangle the heterogeneity in the period before diabetes for further risk stratification. Disclosure T. Hung: None. D. Hua: None. Z. Li: None. R.N. Ekanayake: None. J. Guo: None. J. Varghese: None.

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