Mitral valve regurgitation - Diagnosis and treatment
How Diabetes Impacts Pulmonary Vascular Dysfunction And Fibrosis
Type 2 diabetes and prediabetes can both significantly impact pulmonary health, highlighting the need for early detection and intervention.
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.
Research has also suggested a potential link between prediabetes and pulmonary functionImage credit: peopleimages.Com – stock.Adobe.Com
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:
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
Significant Pulmonary, Upper Limb Function Declines In Ambulatory Patients With DMD
The progression of pulmonary and upper-limb function decline before and after loss of ambulation (LoA) varied among a cohort of patients with Duchenne muscular dystrophy (DMD), according to a study published in PLoS One.1 The findings suggest that clinical trials assessing treatments for patients with declining lung or upper limb function, which typically limit their populations to nonambulatory patients, could also include ambulatory patients.
DMD is a rare genetic condition that causes progressive muscle loss and weakness typically beginning in early childhood.2 An estimated 6 per 100,000 individuals in Europe and North America have DMD, and there is currently no cure. Past research suggests that most patients with DMD experience similar stages of disease progression, with LoA occurring in their teenage years and upper limb and pulmonary deficits following.1
"Alongside therapeutic advances for ambulatory patients, the development of therapeutics for DMD patients in later stages of the disease is a priority," the study authors wrote. "To this end, drug developers have evaluated treatment effects on pulmonary and upper limb function because these functions are the next to decline in patients who have started to lose ambulatory function. Many of the trials targeting these end points have required patients to be nonambulatory at baseline, motivated in part by natural history data showing reliable declines in upper limb and pulmonary function among nonambulant patients."
The study suggests that ambulation status may not necessarily predict early lung or upper limb function declines in DMD, with some ambulatory patients having early declines in these measures.Image credti: Nana_studio - stock.Adobe.Com
In their study, they assessed and quantified trajectories of ambulatory, pulmonary, and upper limb function before LoA and of nonambulatory measurements after LoA. They also explored the sequence of pulmonary and upper limb function changes relative to LoA and assessed potentially prognostic markers for the onset of LoA. Lung function was assessed by forced vital capacity (FVC %-predicted), and scores on the performance of upper limb (PUL) 1.2 measure assessed arm function.
The analysis included 51 patients with DMD who experienced LoA during follow-up in the PRO-DMD-01 natural history study (NCT01753804). The mean age at LoA was 12.7 years, the mean FVC %-predicted was 78.6%, the mean PUL score was 64. While there were smaller mean rates of annual decline in FVC <80%-predicted and PUL 1.2 total scores prior to LoA vs after LoA, these differences were not significant (P = .21, P = .20, respectively).
Approximately half of patients already had a FVC <80%-predicted by the time of LoA, and the rest of the patients experienced this milestone by 2 years post LoA. Regarding PUL 1.2, about 75% of patients had scores lower than 6 at the time of ambulation loss, with the rest experiencing this milestone by 1.5 years following LoA. More than half of patients experienced both FVC <80%-predicted and PUL 1.2 entry scores less than 6 on the same timeline, meaning both milestones occurred either before LoA, with LoA, or after LoA.
These findings imply that ambulation status may not necessarily predict early lung or upper limb function declines, with some ambulatory patients having early declines in these measures. In terms of DMD clinical trial enrollment, the authors argue it should be based on pulmonary and upper limb function thresholds in broad populations that include patients regardless of ambulatory status.
The study's small sample size for LoA events limited its statistical power and prevented the investigation of other factors that could impact outcomes at the same time as LoA, but it also had strengths. These included the prospective collection of natural history data and the selection of patients with comprehensive data on functional assessments, according to the authors.
"Heterogeneous ordering of milestones across functional domains and individual subjects suggests that composite end points for clinical trials, particularly composite time-to-event end points (e.G., time to first clinically meaningful progression in any functional domain) could be helpful for measuring drug effects," the authors wrote. "Such composite outcomes would be sensitive to treatment effects across functional domains and would address the heterogeneity in rates and timing of progression across patients and domains that is characteristic of DMD."
There is an increasing need to assess long-term milestones in DMD as patients live longer and open-label extension or post-market studies are needed for treatments granted conditional or accelerated FDA approval, the authors noted. Therefore, effort should be dedicated to developing and validating composite outcomes that can measure drug efficacy.
"There is heterogeneity across patients in age at LoA and in the ordering and magnitude of deficits in pulmonary and upper limb function before and after LoA," the authors concluded. "Enriching trials for patients with declining pulmonary or upper limb function is achievable without restricting eligibility to non-ambulatory patients; this is particularly important when outcomes of interest evaluate parameters unrelated to lower extremity function such as pulmonary and upper limb function end points."
References
1. McDonald CM, Signorovitch J, Mercuri E, et al. Functional trajectories before and after loss of ambulation in Duchenne muscular dystrophy and implications for clinical trials. PLoS One. Published online June 3, 2024. Doi:10.1371/journal.Pone.0304099
2. Duchenne muscular dystrophy (DMD). Muscular Dystrophy Association. Accessed July 26, 2024. Https://www.Mda.Org/disease/duchenne-muscular-dystrophy
Heart Valve Disease Which Increases Risk Of Strokes And Heart Attacks Is Lurking Undiagnosed In ONE QUARTER Of Supposedly 'healthy' Brits, Study Finds
More than a quarter of apparently healthy over-60s have undiagnosed heart valve disease, a landmark study suggests.
For the first time, research has revealed the number of Britons who unknowingly have the condition – which can increase the chances of heart attack and stroke.
Heart scans were carried out on almost 4,500 symptomless adults, with 28 per cent found to have heart valve disease.
Cases were typically more severe with age, leading researchers to suggest it could one day lead to targeted screening of those most at risk.
Blood flows through the heart and around the body in one direction.
More than a quarter of apparently healthy over-60s have undiagnosed heart valve disease, a landmark study suggests
Vassilios Vassiliou, clinical professor of cardiac medicine at UEA's Norwich Medical School, said the study also showed the older a person is, the higher their chance of having a valve issue
For the first time, research has revealed the number of Britons who unknowingly have the condition – which can increase the chances of heart attack and stroke (file pic)
The four heart valves – pulmonary and tricuspid on the right, and aortic and mitral on the left of the heart – control the blood flow.
Heart valve disease is when one or more do not work as they should.
Researchers from the University of East Anglia examined patients from Norfolk, West Midlands, and Aberdeen using echocardiography, an ultrasound of the heart.
Vassilios Vassiliou, clinical professor of cardiac medicine at UEA's Norwich Medical School, said: 'Our findings showed more than 28 per cent of these adults had some form of valve disease, although reassuringly it was only mild in the majority of the cases.
'The data also indicated… that the older a person is, the higher their chance of having a significant valve issue.'
The main issues included valve stenosis – when a valve does not open fully, restricting blood flow – and valve regurgitation – when a valve does not close properly, allowing blood to leak back in the wrong direction.
Both can force the heart to work harder and in time, raise the risk of a heart attack, stroke or other heart conditions.
Symptoms include breathlessness, chest pain, feeling weak, dizzy or tired, swollen ankles and feet, and chest or neck palpitations.
Further studies are needed to see how screening could be used to help manage the disease, said the paper in the European Heart Journal.
UEA's Norwich Medical School took part in the study, which found that of almost 4,500 symptomless adults, 28 per cent had heart valve disease
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