Introduction

Type 2 diabetes mellitus (T2DM) may adversely affect the lungs through mechanisms similar to other diabetic complications. Chronic hyperglycemia promotes collagen and elastin glycation, alveolar-capillary membrane thickening, accumulation of advanced glycation end-products, inflammation, oxidative stress, and pulmonary microangiopathy, leading to impaired lung mechanics and gas exchange. Observational studies suggest that poor glycemic control, reflected by higher glycated hemoglobin (HbA1c) levels, is associated with lower FEV₁ and FVC, although findings remain inconsistent due to methodological heterogeneity and inadequate adjustment for confounders. It would be important to explore the association between HbA1c and pulmonary function and evaluate the lung as a potential target organ in diabetes.

Aim

To evaluate and quantify the association between HbA1c values and pulmonary function in adults with T2DM.

Study Selection Criteria

• Studies (obser­vational designs: such as cross-sectional assessments or baseline data from cohort studies) enrolling adult patients with confirmed T2DM and reported spirometric outcomes obtained through standardized testing procedures, were included in the analysis. 
• Eligible studies were required to categorize participants into good vs. poor glycemic control, typi­cally based on HbA1c thresholds defined within each study.

Methods

Study Design

Outcomes

Results

• The systematic review and meta-analysis included six studies, providing the details of 944 adults with T2DM from India, Saudi Arabia, and Colombia. The included studies were observational in design, primarily cross-sectional, and evaluated pulmonary function based on spiro­metric parameters. Glycemic control was categorized as per the study-specific HbA1c thresholds, ranging from 7.0% to 8.0%. All studies provided extractable data for FEV1 and FVC, five studies (n=801), provided extractable data for the FEV1/FVC ratio.
• Individuals with poor glycemic control exhibited substantially lower absolute spirometric volumes. Patients with poor glycemic control had lower FEV1, (pooled mean difference: -0.16 L; 95% CI –0.25 to –0.07; p < 0.001) and reduced FVC (pooled mean difference of –0.24 L; 95% CI –0.35 to –0.14; p < 0.001), as compared to those with good glycemic control. 
• On the contrary, patients in poor-control group had a slightly higher FEV1/FVC ratio (MD: 1.61 percentage points, 95% CI 0.50 to 2.73; p = 0.005), as compared to the good-control group. There was no evidence of statistical heterogeneity (I2 = 0%) in all pooled analyses. 
• The reduction in FEV1 and FVC occurred without a corresponding decrease in the FEV1/FVC ratio, suggesting preserved airflow despite lower lung volumes. This pattern is more consistent with possible restrictive physiology than with obstructive airway impairment.

Conclusions

• This systematic review and meta-analysis demonstrated that poor glycemic control in T2DM was associated with lower FEV1 and FVC, with a preserved FEV1/FVC ratio suggesting a possible restrictive rather than obstructive pattern. 
• The meta-analysis had distinct strengths including, consistent pooled spirometric estimates with minimal heterogeneity, biological plausibility supported by established mechanisms, and one of the first quantitative comparisons of lung volumes across HbA1c groups.
• On the contrary, a predominant cross-sectional nature of data, residual confounding, the inability of HbA1c to reflect long-term glycemic burden, possible exposure misclassification, and reliance on absolute spirometric values, limiting assessment of clinical abnormality were the limitations of the meta-analysis.
• The observational nature of the findings warrants a confirmation through longitudinal studies with lung volume assessments and adjustment for key confounders.

PLoS One. 2026 Aug 13;21(8):e0355628. doi: 10.1371/journal.pone.0355628.