# Surfactant Protein D Mediates the Association Between Smoking and Type 2 Diabetes Mellitus Incidence in the Spanish Adult Population: Di@bet.es Study

**Authors:** Wasima Oualla-Bachiri, Ana Lago-Sampedro, Eva García-Escobar, Cristina Maldonado-Araque, Viyey Doulatram-Gamgaram, Marta García-Vivanco, Fernando Martín-Llorente, Juan Luis Garrido, Elías Delgado, Felipe J. Chaves, Luis Castaño, Alfonso Calle-Pascual, Josep Franch-Nadal, Gabriel Olveira, Sergio Valdés, Gemma Rojo-Martínez

PMC · DOI: 10.3390/jox15060184 · Journal of Xenobiotics · 2025-11-01

## TL;DR

This study finds that surfactant protein D partially explains how smoking increases the risk of type 2 diabetes in the Spanish population.

## Contribution

It identifies SP-D as a mediator linking smoking to type 2 diabetes risk in an adult cohort.

## Key findings

- Smoking and high SP-D levels independently increase the risk of type 2 diabetes.
- SP-D mediates 14% of the effect of smoking on type 2 diabetes incidence.
- No significant association was found between air pollutants and SP-D levels.

## Abstract

It is well known that environmental factors influence the risk of type 2 diabetes mellitus (T2DM). Several studies have linked the xenobiotics present in tobacco or air pollutants to T2DM development, although the underlying mechanisms remain unclear. Surfactant protein D (SP-D), an immune component released into the bloodstream after lung injury, has been associated with metabolic diseases. The aim of this study was to investigate whether SP-D mediates the effects of smoking or air pollution exposure on T2DM risk in the Spanish adult population. Socio-demographic, lifestyle (including smoking status) and clinical data from 2155 participants from the Di@bet.es cohort were analyzed. Annual concentrations of PM10, PM2.5, SO2, CO and NO2 according to participants’ residential address codes were used to study air pollution exposure. T2DM was diagnosed at baseline and after 7.5 years of follow-up. SP-D serum levels were measured by ELISA and categorized as above or below the 25th percentile. Our results revealed a higher percentage of smokers in the high SP-D category; however, no associations were observed between air pollutants (PM10, PM2.5, SO2, CO) and SP-D categories. Both smoking and elevated SP-D levels were found to increase the risk of T2DM independently. Mediation analysis indicated that SP-D mediates 14% of the effect of smoking on T2DM incidence in the Spanish adult population.

## Linked entities

- **Proteins:** HOXD13 (homeobox D13)
- **Chemicals:** SO2 (PubChem CID 1119), CO (PubChem CID 281), NO2 (PubChem CID 946)
- **Diseases:** type 2 diabetes mellitus (MONDO:0005148), T2DM (MONDO:0005148)

## Full-text entities

- **Genes:** SFTPD (surfactant protein D) [NCBI Gene 6441] {aka COLEC7, PSP-D, SFTP4, SP-D}
- **Diseases:** lung injury (MESH:D055370), metabolic diseases (MESH:D008659), T2DM (MESH:D003924)
- **Chemicals:** NO2 (MESH:D009585), SO2 (MESH:D013458), PM10 (-), CO (MESH:D002248)
- **Species:** Nicotiana tabacum (American tobacco, species) [taxon 4097]

## Full text

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## Figures

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## References

53 references — full list in the complete paper: https://tomesphere.com/paper/PMC12641695/full.md

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Source: https://tomesphere.com/paper/PMC12641695