Metabolic factors modulating the connection between diabetes and pulmonary alterations

Publication type

Journal Article

Authors

Publication date

March 1, 2026

Summary:

OBJECTIVE:
Type 1 and 2 diabetes have been variably associated with reduced forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC), but mechanisms remain unclear. This study examined the role of glucose and insulin metabolism for pulmonary function across diabetes (sub)types and normal glucose tolerance as the control (CON) in the German Diabetes Study (GDS) and assessed causality by Mendelian randomization (MR) analyses in independent cohorts.

RESEARCH DESIGN AND METHODS:
In GDS, 426 spirometry measurements of participants with type 1 diabetes, 482 of participants with type 2 diabetes, and 244 of CON were cross-sectionally analyzed after phenotyping, including Botnia clamps for insulin sensitivity (M value), secretion, and clearance. Associations between metabolic measures and lung function were assessed using generalized linear models, adjusting for confounders. MR analysis used data from the MAGIC (Meta-Analyses of Glucose and Insulin-Related Traits Consortium) consortium (HOMA-insulin resistance [IR], n = 37,037) and the UK Household Longitudinal Study (pulmonary function, n = 321,047).

RESULTS:
In GDS, higher M value (all β > 0.18, P < 0.0001) and insulin clearance (all β = 0.05, P < 0.050) were associated with higher FEV1 and FVC. Compared with type 1 diabetes and CON, type 2 diabetes had lower FEV1 and FVC, which associated with M value (all β > 0.17, P < 0.050). FEV1 was associated with daily insulin doses in type 1 diabetes (β = −0.21, P = 0.0006). FEV1 was associated with type 2 diabetes (β = −0.19, P = 0.0052), severe insulin resistant (β = −0.27, P = 0.039), and mild age-related diabetes (β = −0.23, P = 0.0033). MR supported a causal association between HOMA-IR and lower FEV1 (β = −0.13, P = 0.0018).

CONCLUSIONS:
Lower FEV1 and FVC in diabetes are linked to insulin resistance, impaired clearance, and higher insulin doses, all of which result in higher insulinemia and likely represent underlying pathogenic mechanisms.

Published in

Diabetes Care

Volume and page numbers

Volume: 49 , p.426 -434

DOI

https://doi.org/10.2337/dc25-2334

ISSN

01495992

Subjects

Notes

© 2026 by the American Diabetes Association

Free access

Readers may use this work for educational, noncommercial purposes if properly cited and unaltered. This publication and its contents may not be reproduced, distributed, or used for text or data mining, machine learning, or other similar technologies without prior written permission. More information is available at https://diabetesjournals.org/journals/pages/license.

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