How Diabetes Impacts Pulmonary Vascular Dysfunction and Fibrosis

A new paper has highlighted the significant impact of type 2 diabetes on pulmonary health, particularly pulmonary vascular dysfunction and fibrosis.

According to the review published in Frontiers in Endocrinology, this intricate relationship between prediabetes, type 2 diabetes, and pulmonary disorders underscores the urgent need for extensive research into prediabetes and its underlying mechanisms to prevent progression to diabetes.¹

Pulmonary complications, such as vascular dysfunction and fibrotic lung disease, significantly increase morbidity and mortality, while also diminishing the quality of life for individuals with type 2 diabetes. Early detection and management of prediabetes with a focus on preventing pulmonary complications may help reduce the risk of developing type 2 diabetes. Understanding and treating pulmonary disorders in these patients can also improve patient outcomes and alleviate the burden of metabolic disorders, making it even more important to target both prediabetes and pulmonary health at the same time.

The review authors found that diabetes, which is traditionally linked to cardiovascular and microvascular complications, can also lead to pulmonary complications through mechanisms such as oxidative stress, dysregulated fibrotic signaling, and chronic inflammation.

Type 2 diabetes is a chronic metabolic condition characterized by insulin resistance and impaired glucose metabolism that affects multiple organs, including the lungs. Research has underscored a significant link between type 2 diabetes and pulmonary vascular disorders, such as pulmonary arterial stiffness and hypertension.

This relationship is marked by problems such as:

• Endothelial dysfunction, where there is damage to the lining of blood vessels
• Vascular remodeling, where there are changes in how blood vessels are structured
• Reduced pulmonary vascular reactivity, where there is a decrease in how well blood vessels in the lungs can react

These issues make it harder for the lungs to get enough oxygen into the blood, and high blood sugar levels in diabetes can make these problems worse by causing increased stress, inflammation, and changes in how insulin works in the body. These changes lead to the growth of smooth muscle in blood vessels, remodeling of lung tissues, and damage from substances called oxidants. Together, these factors make it harder for the lungs to function properly, which can cause symptoms like difficulty exercising and feeling short of breath, similar to what happens in pulmonary hypertension.

Research has also suggested a potential link between prediabetes and pulmonary function, with studies linking prediabetes and breathing problems, showing how diabetes-related changes in body chemistry affect lung function. Prediabetes is characterized by insulin resistance, unhealthy lipid levels, and chronic low-grade inflammation, and it may adversely affect the lungs, similar to how it impacts other organ systems.

These metabolic disturbances can damage the blood vessels in the lungs and the lung tissue itself, potentially leading to conditions such as pulmonary fibrosis. Additionally, elevated blood sugar and lipid levels in prediabetes can increase oxidative stress and inflammation in lung cells, which activate pathways that cause tissue scarring and remodeling. This damage is further exacerbated by disrupted lipid metabolism and the accumulation of harmful compounds, leading to more severe lung damage.

Prediabetes can also disturb the production and availability of nitric oxide (NO)—a critical molecule for maintaining healthy blood vessels—by impairing the activity of enzymes involved in NO production. This leads to blood vessel dysfunction, increased vessel constriction, and reduced vascular relaxation, all of which contribute to cardiovascular complications like hypertension and atherosclerosis. The imbalance in NO levels, alongside the increase of inflammatory and fibrotic signaling molecules, underscores the importance of early detection and intervention in prediabetes to prevent both cardiovascular and pulmonary complications.

While prediabetes has mainly been connected to heart and small blood vessel problems in the past, understanding how it affects lung health is now seen as very important, the review authors emphasized.

“The transition from prediabetes to overt T2DM [type 2 diabetes mellitus] may further intensify these pulmonary complications, highlighting the importance of early intervention and preventive measures,” the authors said. “However, the precise mechanisms linking prediabetes to pulmonary pathology remain incompletely understood. Hence, more research is needed to look at the relationship between prediabetes and pulmonary dysfunction, including reduced pulmonary function, an elevated risk of respiratory infections, and maybe the onset of pulmonary fibrosis.”

Outside of this review, other research published in the International Journal of Chronic Obstructive Pulmonary Disease found that patients who have both type 2 diabetes and chronic obstructive pulmonary disease (COPD) face higher rates of both all-cause and respiratory-cause mortality compared with those without COPD.² The study revealed that diabetes and COPD share an inflammatory nature and similar risk factors, leading to significant overlap and interaction between these 2 conditions.

The all-cause mortality rate was significantly higher in individuals with COPD (448.7 per 1000 person-years) compared with those without COPD (296.6 per 1000 person-years). Similarly, the respiratory mortality rate was 3.03 times higher for those with COPD (129.0 per 1000 person-years) than for those without COPD (26.6 per 1000 person-years). By the end of the study, the all-cause mortality survival probability was approximately 25% for those with COPD and 40% for those without COPD; the respiratory mortality survival probability was about 75% for those with COPD, compared with nearly 100% for those without COPD. The study also found that while COPD was associated with moderately increased cardiovascular mortality rates, this association was not significant after adjusting for preexisting cardiovascular disease.

Together, these findings underscore the importance of further research into the interplay between diabetes and respiratory conditions like COPD and pulmonary fibrosis.

References

1. Mzimela N, Dimba N, Sosibo A, Khathi A. Evaluating the impact of type 2 diabetes mellitus on pulmonary vascular function and the development of pulmonary fibrosis. Front Endocrinol. Published online July 10, 2024. doi:10.3389/fendo.2024.1431405
2. McCormick B. COPD in patients with type 2 diabetes associated with increased overall, respiratory mortality. AJMC®. June 21, 2023. Accessed July 12, 2024. https://www.ajmc.com/view/copd-in-patients-with-type-2-diabetes-associated-with-increased-overall-respiratory-mortality