# The Association Between Measures of Prepregnancy Insulin Resistance and Sensitivity with Subsequent Risk of Gestational Diabetes

**Authors:** Shalmali Bane, Fei Xu, Assiamira Ferrara, Sneha Sridhar, Charles P Quesenberry, Monique M Hedderson

PMC · DOI: 10.1210/jendso/bvaf227 · Journal of the Endocrine Society · 2026-01-12

## TL;DR

Higher insulin resistance before pregnancy is linked to a greater risk of developing gestational diabetes, especially in certain racial and ethnic groups.

## Contribution

This study identifies prepregnancy insulin resistance as a risk factor for gestational diabetes with race/ethnicity-specific associations.

## Key findings

- Higher HOMA-IR levels were associated with increased odds of gestational diabetes.
- The association was strongest in Asian and non-Hispanic Black populations.
- No significant link was found between HOMA-β and gestational diabetes risk.

## Abstract

Little is known about the association between prepregnancy homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of β-cell function (HOMA-β) levels and risk of gestational diabetes mellitus (GDM).

To examine the association between prepregnancy levels of HOMA-IR and HOMA-β and risk of GDM and whether these associations vary by race and ethnicity.

We conducted a nested case-control study among women who had a serum sample from 1984 to 1996 used to measure glucose and insulin and a subsequent pregnancy from 1984 to 2009. GDM cases (n = 254) were matched with 2 randomly selected control subjects (n = 497) on serum collection date, age at collection, number of intervening pregnancies, and age at delivery. We used conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for GDM by HOMA-IR and HOMA- β, overall and stratified by race and ethnicity.

Increasing levels of HOMA-IR were associated with higher odds of GDM (adjusted OR for 1 SD increase: 1.31 [95% CI 1.12,1.54]) and tertile 3 compared to tertile 1 (3.04 [95% CI 1.81, 5.12]). Models stratified by race/ethnicity suggest this association was significant among Asian and non-Hispanic Black populations for tertile 3 (3.83 [95% CI 1.39, 10.57] and 2.18 [95% CI 1.03, 4.61], respectively). Among non-Hispanic Black individuals, a 1 SD increase in HOMA-IR also increased risk of GDM (OR: 1.59, 95% CI 1.17, 2.17). There was no significant association between HOMA-IR and GDM among non-Hispanic White or Hispanic individuals. There was no association between HOMA-β and GDM risk.

Higher HOMA-IR levels before pregnancy were associated with an elevated risk of GDM.

## Linked entities

- **Chemicals:** glucose (PubChem CID 5793), insulin (PubChem CID 70678557)
- **Diseases:** gestational diabetes mellitus (MONDO:0005406), gestational diabetes (MONDO:0005406)

## Full-text entities

- **Genes:** HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, HK1 (hexokinase 1) [NCBI Gene 3098] {aka CNSHA5, HK, HK1-ta, HK1-tb, HK1-tc, HKD}
- **Diseases:** glucose intolerance (MESH:D018149), stillbirth (MESH:D050497), T2D (MESH:D003924), adiposity (MESH:D018205), Insulin Resistance (MESH:D007333), gestational hypertension (MESH:D046110), cardiovascular disease (MESH:D002318), polycystic ovarian syndrome (MESH:D011085), obesity (MESH:D009765), GDM (MESH:D016640), preeclampsia (MESH:D011225), diabetes (MESH:D003920), hyperglycemia (MESH:D006943)
- **Chemicals:** glucose (MESH:D005947), alcohol (MESH:D000438)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12936787/full.md

## References

39 references — full list in the complete paper: https://tomesphere.com/paper/PMC12936787/full.md

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Source: https://tomesphere.com/paper/PMC12936787