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Causal Link Found for Type 2 Diabetes and Lung Complications

Liverpool — High blood sugar in patients with type 2 diabetes, including prediabetes, was found to be causally linked to lung disorders in the first study of its kind into type 2 diabetes and lung dysfunction.

Study lead Inga Prokopenko, PhD, professor of e-One Health at the University of Surrey, Guildford, presented the findings at the Diabetes UK professional conference on behalf of the Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC) consortium.

"We show that higher blood glucose levels in type 2 diabetes cause reduction in lung function by lowering two classical spirometry measures - forced vital capacity [FVC] and forced expiratory volume in 1 second [FEV1]," she highlighted. 

"This means that pulmonary dysfunction, such as restrictive lung disease, is a complication of type 2 diabetes," she said. "We propose that clinicians do spirometry tests for people at risk, or with diabetes, to detect lung dysfunction early and to make individuals aware of this complication. 

"Clinicians may then investigate it further and manage the respiratory complications. Currently, this is not part of routine practice, but we propose that it should become so." 

Lung conditions, including restrictive lung disease, fibrosis and pneumonia, were known to be more common in people with type 2 diabetes, but whether there was a direct link between type 2 diabetes and damage to the lungs was unknown until now. 

Professor Prokopenko told Medscape News UK that she had a family member with type 2 diabetes who continuously suffered from upper respiratory tract conditions, which started only after their diagnosis with type 2 diabetes. "There was no clinical strategy to investigate such lung problems further and they were told this was due to their diabetes. This prompted me to explore further the genetic correlation between type 2 diabetes and lung function traits, and this led me to the finding I am presenting now."

Large Study Using UK Biobank Data

Restrictive lung diseases are found in 16-20% of individuals with type 2 diabetes. During the COVID-19 pandemic, it was found that lung fibrosis was more frequent in people with type 2 diabetes as compared with the general population, but a possible pathophysiological explanation was lacking, explained Professor Prokopenko.

The researchers analysed data from a diverse group of nearly 500,000 participants in 17 major studies, including the UK Biobank. Controlling for factors including smoking and sedentary behaviour, the team used a statistical technique called Mendelian randomisation to understand whether high blood sugar levels were linked to impaired lung function, and whether one was causing the other. Lung function was measured using FVC and FEV1.

Until the availability of large-scale, genome-wide association studies for these conditions, including datasets such as UK Biobank, electronic health records and development of methodology for Mendelian randomisation, "a clear dissection of this causality was not possible in humans", remarked Professor Prokopenko.

Briefly explaining some of the methodological background, she said that: "Mendelian randomisation uses a 'natural randomisation' of DNA variant alleles in the population, enabling the dissection of causal relationships in human studies while avoiding any unethical experimentation."

In terms of the biological mechanism predisposing people with type 2 diabetes to lung complications, Prof Prokopenko explained that their study did not specifically investigate the biological mechanism in this study, but said that: "Overall, vascular endothelial dysfunction is the main feature of diabetes, and this involves alteration in several biological processes, from hyperglycaemia to inflammatory activation, the latter being one of the possible explanations of the effects on respiratory complications in type 2 diabetes." 

Turning to the implications of the finding for clinical practice, Prof Prokopenko explained that more studies and replication were needed before consolidation of the causal effect into guidance or similar, but that patients found to have lower spirometry readings might benefit from a glucose test to check for pre/diabetes. "And vice versa, in pre-diabetes and diabetes, if lung function is somehow compromised people could get respective expert consultation."

Other suggestions might include early prevention, for example more physical activity and some weight loss. "With this approach, the prevention would work both ways by lowering glucose levels, which might lead to fewer respiratory complications," she pointed out.

Answers a 'Long-Standing Question'

Commenting on the findings Elizabeth Robertson, PhD, director of research at Diabetes UK, said: "This important research answers a long-standing question, revealing for the first time that lung disorders can be a direct complication of type 2 diabetes.

"Lung conditions can be life-changing and life-limiting, and it is crucial that healthcare professionals are aware of the impact of high blood sugar levels on lung health. Research must now investigate how best to prevent, monitor and treat lung disorders in people with type 2 diabetes."

Adrian Heald, consultant physician in diabetes and endocrinology at Leighton and Macclesfield Hospitals, Cheshire, commented on the work: "I'm curious about whether you've looked at prediabetes too, because we have work from the DARE study showing a very much higher prevalence of asthma in the years – up to 10 to 15 years – before the formal diagnosis of type 2 diabetes, as [discussed] separately at this meeting. This gives support from a longitudinal data perspective to Professor Prokopenko's findings."

Professor Prokopenko replied to the comment. "This is exactly our point, because we looked at people leading up to diabetes. A tiny change in glucose levels can lead to a change in lung function," she said. 

Dr Heald's study showed a greater number of hypertension and asthma diagnoses in people who went on to develop type 2 diagnoses than those who did not, suggesting an early phase of potentially-related disease activity well before any clinical diagnosis of diabetes is made. This may relate to both vascular changes and systemic inflammation. 

Professor Prokopenko has no conflicts to declare. Dr Heald and Dr Robertson have no disclosures.