# Serum Insulin-like Growth Factor-II Is Associated with Poor Poststroke Outcomes in Males: A Secondary Analysis

**Authors:** Christian Glamheden, N. David Åberg, Gustaf Gadd, Daniel Åberg

PMC · DOI: 10.3390/ijms26125525 · International Journal of Molecular Sciences · 2025-06-09

## TL;DR

Low levels of a blood protein called IGF-II in the early stages after a stroke are linked to higher death rates in men, but not in women.

## Contribution

This study reveals a sex-specific link between low IGF-II and poststroke mortality in males.

## Key findings

- Males with the lowest IGF-II levels had nearly double the risk of poststroke death.
- No significant association between IGF-II and outcomes was found in females.
- The link between IGF-II and functional outcomes in males was not independent of stroke severity.

## Abstract

The insulin-like growth factor (IGF) system has significance for poststroke outcomes. Previously, we reported that low serum IGF-II (s-IGF-II) in the acute phase is associated with poststroke mortality, and that IGF-II is lower among males. Given the known interactions of the IGF system and estrogen receptor signaling, s-IGF-II may have sex-specific effects. In this study, we conducted a secondary analysis of sex differences in s-IGF-II and poststroke functional outcomes and mortality after ischemic stroke (IS) in the Sahlgrenska Academy Study on Ischemic Stroke (SAHLSIS, males; n = 315, females; n = 177). Functional outcomes were assessed using the modified Rankin scale (mRS) at 3 months and 2 years poststroke. Survival was recorded for 7 years or until death. Males in the lowest quintile of acute s-IGF-II had a higher poststroke mortality, with a crude hazard ratio [HR] of 2.52 (95% confidence interval [CI]) 1.59–3.99) and an adjusted HR of 1.83 (95% CI 1.09–3.06). No corresponding significant association was observed in females. Although acute s-IGF-II was crudely associated with poor functional outcomes among males after 3 months and 2 years, these associations were not independent of initial stroke severity in adjusted models. In conclusion, low levels of acute s-IGF-II are linked with poststroke mortality among males, but not significantly in females. Further studies are, however, warranted with sex hormone analysis, consideration of specific cause of death, and more females.

## Linked entities

- **Proteins:** IGF2 (insulin like growth factor 2)
- **Diseases:** ischemic stroke (MONDO:1060198)

## Full-text entities

- **Genes:** ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, IGF2 (insulin like growth factor 2) [NCBI Gene 3481] {aka C11orf43, GRDF, IGF-II, PP9974, SRS3}
- **Diseases:** IS (MESH:D002544), stroke (MESH:D020521), death (MESH:D003643)

## Full text

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## Figures

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## References

38 references — full list in the complete paper: https://tomesphere.com/paper/PMC12192941/full.md

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Source: https://tomesphere.com/paper/PMC12192941