the lung & diabetes mellitus

April 12, 2023 amr badreldin hamdy MD FCCP 1

The Lung and Diabetes Mellitus

Amr Badreldin Hamdy

MD FCCP

Diabetes mellitus is associated with widespread metabolic, hormonal and microvascular abnormalities as well as disturbances of the function of many organic systems.

Consequently, the kidneys, eyes, cardiovascular system and the respiratory system can be damaged.

The lung is a target organ for diabetic microangiopathy, in both type I and type II diabetes.

The pathogenesis of the major long-term complications of DM is currently thought to involve both a microangiopathic process and non-enzymatic glycosylation of tissue proteins, thus rendering the lungs a target organ.

Evidence of pulmonary microangiopathy is the thickening of the alveolar capillary and pulmonary arteriolar walls and decreased lung capillary blood volume in patients with type I DM.

There is a random pattern of tissue involvement in diabetic patients.

The most likely factors responsible for the development of abnormal lung mechanics in DM are the alterations of the lung connective tissue at a biochemical level.

Changes in either collagen or elastin components could significantly affect the behavior of the other, since the normal elastic and compliant properties of the lung require that all connective tissue elements work in harmony and are in proper spatial orientation with one another.

The strength and stability of the connective tissue is provided by the cross-link formation of both collagen and elastin components and the stocking mesh arrangement of these fibers..

The structural changes of the lung parenchyma is diabetics may be:

1 .Narrowing of the alveolar space .

2 .Flattening of the alveolar epithelium.

3 .Expansion of the interstitium.

4 .Involvement of the pulmonary vessels.

5 .Involvement of the BM of the alveolar epithelium, bronchial epithelium and the pulmonary capillaries.

Pulmonary complications of DM

1 .Infections .

2 .Pulmonary edema .

3 .Disordered breathing during sleep .

4 .Reduction of elastic recoil of the lungs .

5 .Decreased DLCO .

6 .Decreased bronchomotor tone .

7 .Increased risk of thromboembolism due to their hypercoagulable state .

8 .Higher prevalence of pulmonary hypertension .

9 .Cigarette smoking in diabetics poses an increased risk of COPD as compared with non-diabetics.

Conclusion

DM can cause impaired lung function, decreased respiratory muscle indurance, diaphragmatic paralysis, dyspnea, pulmonary hypertension, pulmonary infections and pulmonary tuberculosis.

Tuberculosis

The prevalence of tuberculosis is increased in diabetic patients.

Pulmonary tuberculosis and diabetes mellitus coexist frequently.

Diabetic patients have an increased tendency to acquire tuberculosis ( four to five times) .

The reported risk of tuberculosis in diabetic patients ranges from 4-14%.

Eight of ten countries with the highest prevalence of diabetes mellitus are labeled by the WHO as high burden states for tuberculosis.

In parts of the world where tuberculosis is endemic, a higher than expected proportion of patients with tuberculosis have diabetes mellitus.

Increased reactivity of tuberculosis lesions is recorded in diabetics.

The duration of diabetes mellitus has no effect on prevalence of pulmonary tuberculosis.

The incidence of lung tuberculosis is increased in uncontrolled diabetics and in patients with severe diabetes requiring large doses of insulin.

Tuberculosis is more aggressive in poorly controlled diabetics.

When persons with diabetes mellitus do not respond in spite of appropriate treatment, they should be screened for tuberculosis, as weakness, sweating and weight loss are common for both tuberculosis and diabetes.

Pulmonary tuberculosis is a common accompaniment of diabetes mellitus and the cause of insulin resistance and brittleness.

Diabetes mellitus and pulmonary tuberculosis includes a severe form and more aggressive course of the disease, a higher tendency to tissue destruction and cavitation, and more common resistance to anti-tuberculosis treatment.

Probable Reasons for the High Association of TB

and DM

Hyperglycemia favors the growth, viability and propagation of tubercle bacilli.

Disturbance in electrolyte balance and local tissue acidosis favor infection.

Impaired phagocytosis and impaired cellular immunity in persons with DM allows for the spread of the disease over neutralizing antibodies in bronchial secretions.

Lower resistance due to vascular damage to lung tissue.

Disordered nutritional balance.

Atypical Chest X-ray Findings

Lower lobe or multiple lobe involvement. Higher incidence of cavity lesions. Higher incidence of pleural effusions. Complete resolution occurs in patients with

HLA A1 and DR2. In patients with HLA A2 and DR3, large

caseous focus of tuberculoma is formed.

Therapy

Patients with type II diabetes on oral therapy may need insulin supplementation or insulin replacement.

Type II patients may require intensification of treatment.

Treatment may be prolonged to nine to twelve months.

Possible therapy related problems may include impaired GIT absorption and the hyperglycemic state that may interfere with achieving adequate tissue levels, alveolar macrophage function and CD 4+ cell function.

Initial hospitalization improves compliance and response to treatment.

As rifampicin induces hepatic enzymes that inactivate sulphonylureas matabolized by the liver, sulphonylureas may become less effective and should probably be avoided.

INH and RIF both lead to abnormal Vit D metabolism and hypocalcemia.

PASA therapy is associated with goitre and hypothyroidism and hypoglycemia.

Pulmonary Infections

DM is a risk factor for pneumonia among patients younger than 40 years.

Patients with DM may be more likely to have recurrent pneumonia.

DM is linked with higher pneumonia related mortality rates (up to an 30% increase).

Patients with longstanding diabetes with complications are at a much greater risk of infections than non-diabetics or diabetics without complications.

Pulmonary infections in DM are characterized by alterations in host defense, in the entire body, and in the lung locally as well in the function of the respiratory epithelium and cilia motility.

Characteristics of Pulmonary Infections

Serious clinical features. Longer duration. More frequent complications. Increased risk of recurrent bacterial

pneumonia. Increased mortality.

Elevated blood glucose levels negatively affect the outcome in diabetic patients with pneumonia, with a mortality risk as high as 30% in cases of uncontrolled DM.

The most common complications of pneumonia in diabetics are:

Pleural effusion.

Empyema.

Bacteremia (especially Klebsiella).

Why are respiratory infections more common

in DM?

A wide range of neutrophil and macrophage functions are impaired e.g. chemotaxis, adherence, phagocytosis, and ability to kill phagocytosed microorganisms with free radicals, superoxides and hydrogen peroxides (the respiratory burst is impaired).

Serum complement levels (e.g. C4) and T-4 lymphocytes are reduced in diabetics.

Increased glucose levels impair collective surfactant D-mediated host defenses of the lung.

Diabetic gastroparesis may increase the risk of aspiration.

Staphylococcus Aureus

Up to 30% of diabetics are nasal carriers of S.aureus as compared to 11% of healthy individuals. The carriage rate is influenced by the degree of glycemic control.

The rate of nasal carriage of S. aureus is directly related to the glycosylated Hb.

On the basis of a high nasal carriage rate, diabetics are thought to be at an increased risk of staphylococcal pneumonia.

Diabetics are at a risk of developing complications of bacteremia in S. aureus pneumonia, with an increase in mortality.

Gram negative aerobic organisms

The predisposition of diabetics to the development of gm-ve aerobic pneumonia is attributed to an increased rate of upper airway colonization and adherence of these organisms.

Anaerobic Organisms

Although DM is not specifically indentified as a risk factor for developing anaerobic pulmonary infections, diabetic patients are probably at risk because of:

# altered cough and clearance mechanisms

# esophageal disorders # depressed mental status (hypoglemic

seizures).

The reduced oxygen supply to tissues as a result of microvascular changes predisposes diabetics to infections by anaerobic microorganisms which grow best under such conditions.

Legionella pneumonia

o The risk of acquiring Legionella pneumonia is increased in diabetics.

o Legionella is associated with excess morbidity and mortality in diabetics.

Aspergillus can cause fungal pneumonia in diabetics.

This infection may present as an intra-cavity mass or mycetoma, acute and chronic pneumonia.

Nosocomial Pneumonia

About 25% of nosocomial pneumonia infections are polymicrobial.

Aerobic gm-ve organisms and staphylococcal infections typically are the most important causes of nosocomial pneumonias in diabetic patients.

Viral Infections

Viral infections in diabetic patients are often complicated with bacterial pneumonia.

Influenza is a substantial cause of morbidity and mortality in diabetics.

Influenza virus grows to significant titers in diabitus lungs.

During epidemics of influenza the rate of pneumonia, ketoacidosis and mortality increase sharply in diabetics.

Prophylactic influenza vaccine is advised in diabetics.

Diabetic patients respond well to pneumococcal and influenza vaccinations making timely and appropriate immunization a cost-effective and efficient method of preventing morbidity from pneumococcal and influenza pneumonia in these patients.

Statin use is said to prevent respiratory infections in persons with diabetes mellitus (as they have immune modulation and anti inflammatory properties.

Effect of Infection on DM

As a response to infection and cytokine release, insulin resistance in peripheral tissues occurs, resulting in the elevation of blood sugar.

Therapy of Pneumonia in DM

Start with antibiotic as soon as possible. Priority should be given to antibiotics from

the group of quinolones and aztreonam (better intracellular penetration and efficacy in immune compromised patients.

Good glycemic regulation because of the influence on the immune system.

Many of the antibiotics used must be adjusted to patients with renal dysfunction.

Avoid aminoglycosides.

Conclusion

Infections with increased frequency may be due to S.aureus, gm-ve organisms such as Klebsiellae, E.coli, Enteroacter, Pseudomonas and Acinetobacter.

Infections with a possibly increased morbidity and mortality may be due to Streptococcus, Legionella and viral infections (influenza).

Pulmonary Function

The finding of abnormal lung function in some diabetes subjects suggests that the lung should be considered a target organ in

diabetes mellitus.

When a person’s blood sugar is higher, and less near the optimal range, his lung function tends to be decreased.

There is increased deterioration of lung function over time in patients with diabetes, particularly with respect to the impact of inhalational delivery of pharmacological agents.

The most consistent abnormalities shown in diabetes mellitus

Reduced lung volumes in young IDDM. Reduced pulmonary elastic recoil in both

young and adult diabetes subjects. Impaired pulmonary diffusion due to a

reduced pulmonary capillary blood volume in the adult group.

Diabetes patients show impaired alveolar gas exchange. There is thickened alveolar epithelium and capillary basal laminae, the latter is suggestive of existing pulmonary microangiopathy.

There is reduced muscle strength in diabetes patients.

Bilateral diaphragmatic paralysis due to phrenic neuropathy, which may explain the unexplained breathlessness and orthopnea.

There is peripheral airway dysfunction in type I diabetes mellitus (in the absence of cigarette consumption, allergies or other common causes of airflow obstruction). Forced oscillation provides a sensitive index of peripheral airway dysfunction.

Forced oscillation is the noninvasive equivalent of dynamic lung compliance. It measures respiratory resistance during resting breathing. It is sensitive enough to detect early inflammatory peripheral airway disease in asymptomatic smokers.

Role of Simple Lung Function Tests

Common simple lung function tests alone are likely to underestimate the prevalence and degree of lung dysfunction in diabetes mellitus patients.

FEV1/FVC are significantly lower in diabetes patients than controls.

Average rate of decline in FEV1 is 71 ml/year in diabetes patients.

An increase in HbAIc is associated with decrease in lung function parameters FEV1 and FVC (impaired glucose auto-regulation is associated with impaired lung function).

In patients with diabetic autonomic neuropathy there is an abnormal basal airway tone due to an alteration in vagal pathway: these patients have a reduced bronchial reactivity and reduced bronchodilation.

Patients with normal CO transfer capacity in the seated posture may show decreased capillary volume in the supine posture relative to normal control subjects. Thus measuring seated and supine CO transfer capacity may diagnose early pulmonary vascular damage.

The most important clinically manifest effect of maternal diabetes on the pulmonary function of the offspring is the increased incidence of the RDS compared with the offspring of non-diabetes mothers, as a result of the inhibitory effects of fetal hyperinsulinemia on pulmonary surfactant formation.

Conclusion

Alteration of lung CT is the most likely pathogenesis mechanism underlying mechanical pulmonary dysfunction in diabetes subjects.

The lung is a target organ for diabetic microangiopathy.

Lung function tests relating specifically to pulmonary microangiopathy include CO transfer capacity and pulmonary capillary blood volume.

References

Pulmonary complications in DM. Recenti Prog. Med. 87(12):623 (1996).

Is the lung a ‘target organ’? Arch. Intern. Med. 150(7): 1385 (1990).

Lung dysfunction in diabetes. Diabetes care 26(6):1915 (2003).

The lung in Diabetes Mellitus. Respiration 66: 12 (1999).

Spirometry and Diabetes. Diabetes Care 27(3): 837 (2004).

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