ReviewThe diabetic lung: Relevance of alveolar microangiopathy for the use of inhaled insulin
Section snippets
Pulmonary pathophysiology in diabetes
Insulin broadly modulates cell growth and metabolism via receptors in the lung. Insulin enhances proliferation of alveolar and bronchial epithelial cells and vascular smooth muscle,14, 15 inhibits apoptosis,16 and promotes vasodilatation.17, 18 Maternal diabetes delays fetal and postnatal lung development.19, 20 Preterm infants of diabetic mothers show accelerated muscularization of small pulmonary arteries that predisposes to neonatal pulmonary hypertension.21 At autopsy, diabetic lungs show
Pulmonary function in diabetes
The major categories of assessment are ventilatory control, mechanical function (volume, flow rates and elastic recoil), and microvascular function (gas exchange).
Relevance to inhaled insulin
Because the lung provides large surfaces and longer residence times for drug absorption, inhaled insulin rapidly reaches peak plasma level and metabolic effect without the invasiveness of subcutaneous injection.84 Comparable glycemia is achieved with supplemental inhaled insulin as with subcutaneous insulin alone,85 and adding inhaled insulin to conventional regimen may improve glycemic control.86, 87 Side effects are minor88 and patient satisfaction is high.89 Such advantage is balanced
Conclusion
Diabetic pulmonary complications are more prevalent than generally recognized. Conventional assessment of microangiopathy (retinopathy, nephropathy, neuropathy) is often complicated by organ failure as secondary complications, and effects of therapy may confound data interpretation. Established indexes of alveolar diffusion-perfusion relations that have been used to evaluate alveolar-capillary integrity independent of physical fitness could be applied to diabetes to provide noninvasive
References (93)
- et al.
An 8-year follow-up of carbon monoxide diffusing capacity in a general population sample of northern Italy
Chest
(2001) - et al.
Influence of maternal diabetes on basement membranes, type 2 cells, and capillaries in the developing rat lung
Dev Biol.
(1984) - et al.
Thickness of the basement membrane of bronchial epithelial cells in lung diseases as determined by transbronchial biopsy
Respir Med.
(1997) - et al.
Capillary basement membrane width in diabetic children
Am J Med.
(1975) - et al.
Technetium 99mTc-DTPA clearance in the evaluation of pulmonary involvement in patients with diabetes mellitus
Respir Med.
(2000) - et al.
Pulmonary complications in diabetes mellitus
Mayo Clin Proc.
(1989) - et al.
Pulmonary function in young insulin-dependent diabetic subjects
Chest
(1986) - et al.
Glycemic control and cardiopulmonary function in patients with insulin-dependent diabetes mellitus
Am J Med.
(1997) - et al.
Relationship between diabetes control and pulmonary function in insulin dependent diabetes mellitus
Am J Med.
(1991) Recruitment of lung diffusing capacityupdate of concept and application
Chest
(2002)
Determination of lung capillary blood volume and membrane diffusing capacity in man by the measurements of NO and CO transfer
Respir Physiol.
Pulmonary membrane diffusing capacity and capillary blood volume measured during exercise from nitric oxide uptake
Chest
Characteristics of pulmonary function in patients with diabetes mellitus
Diabetes Res Clin Pract.
Lung function in patients with diabetes mellitus
Respir Med.
Pulmonary function in patients with diabetes mellitus
Am J Med Sci.
Efficacy of inhaled human insulin in type 1 diabetes mellitusa randomised proof-of-concept study
Lancet
Treating diabetes with aerosolized insulin
Chest
Effect of glycemic control on microvascular complications in patients with type I diabetes mellitus
Am J Med.
Intensified conventional insulin treatment retards the microvascular complications of insulin-dependent diabetes mellitus (IDDM)the Stockholm Diabetes Intervention Study (SDIS) after 5 years
J Int Med.
Glucose control and the renal and retinal complications of insulin-dependent diabetes
JAMA
Heart-lung interactions in the transport of oxygen
Elasticity of human lungs in relation to age
J Appl Physiol.
The alveolar-arterial oxygen differenceits size and components in normal man
Acta Physiol Scand.
Longitudinal effects of aging on lung function at rest and exercise in healthy active fit elderly adults
J Appl Physiol.
A hemodynamic comparison of young and older endurance athletes during exercise
J Appl Physiol.
Effects of aging, sex, and physical training on cardiovascular responses to exercise
Circulation
Predictors of longitudinal change in diffusing capacity over 8 years
Am J Respir Crit Care Med.
Response to exercise after bed rest and after training
Circulation
Coordinated adaptation of oxygen transport in cardiopulmonary disease
Circulation
Stimulation of DNA synthesis in cultured rat alveolar type II cells
Exp Lung Res.
Biosynthesized matrix provides a key role for survival signaling in bronchial epithelial cells
Am J Physiol Lung Cell Mol Physiol.
Insulin inhibits apoptosis of macrophage cell line, THP-1 cells, via phosphatidylinositol-3-kinase-dependent pathway
Arterioscler Thromb Vasc Biol.
Pulmonary vasodilation in the rat by insulin in vitro could indicate potential hazard for inhaled insulin
Diabetologia
Vasoreactivity and prostacyclin release in streptozotocin-diabetic ratseffects of insulin or aldose reductase inhibition
Br J Pharmacol.
Epidermal growth factor and lung development in the offspring of the diabetic rat
Pediatr Pulmonol.
Increased muscularization of small pulmonary arteries in preterm infants of diabetic mothersa morphometric study in noninflated, noninjected, routinely fixed lungs
Pediatr Pathol Lab Med.
Nodular fibrosis of the lung in diabetes mellitus
Virchows Arch.
Changes in the lungs in diabetes mellitus
Arkh Patol.
Basal lamina of alveolar epithelium and capillariesquantitative changes with aging and in diabetes mellitus
Am Rev Respir Dis.
Diabetes mellitus induces a thickening of the pulmonary basal lamina
Respiration
Changes in lung morphologic features and elasticity caused by streptozotocin-induced diabetes mellitus in growing rats
Am Rev Respir Dis.
Alterations of lung structure in experimental diabetes, and diabetes associated with hyperlipidaemia in hamsters
Eur Respir J.
Alterations in granular (type II) pneumocyte ultrastructure by streptozotocin-induced diabetes in the rat
Lab Invest.
Experimental diabetes and the lung. II. In vivo connective tissue metabolism
Am Rev Respir Dis.
Experimental diabetes and the lung. I. Changes in growth, morphometry, and biochemistry
Am Rev Respir Dis.
Obesity-induced hyperplastic lung growth
Am Rev Respir Dis.
Cited by (80)
Well-controlled vs poorly-controlled diabetes in patients with COVID-19: Are there any differences in outcomes and imaging findings?
2020, Diabetes Research and Clinical PracticeCitation Excerpt :Several hypotheses exist for the role of hyperglycemia in the progression of viral respiratory infections. Elevated blood glucose levels may negatively impact pulmonary function, as well as suppressing the immune system and increasing the production of inflammatory cytokines [25–28]. In addition, angiotensin-converting enzyme 2 (ACE2), one of the main receptors for SARS-CoV-2, is expressed within the pancreas, suggesting that this novel coronavirus can directly damage pancreatic islets [29].
Lung function in patients with diabetes mellitus
2016, Revue de Pneumologie CliniqueEffects of exercise intensity compared to albuterol in individuals with cystic fibrosis
2015, Respiratory MedicineCitation Excerpt :The diffusion of the lungs for nitric oxide is theoretically based solely on membrane conductance as nitric oxide is scavenged 280 times faster by hemoglobin than CO, meaning its uptake into the blood is nearly instantaneous. For this reason, DLNO is considered a relatively direct measure of alveolar-capillary membrane conductance (DMNO), as the diffusion resistance of the blood is trivial [34–38]. In addition, more recent work has demonstrated that DLNO is closely related to anatomical abnormalities determined using computed tomography in patients with CF [39].
Bone Marrow-Derived C-Kit<sup>+</sup> Cells Improved Inflammatory IL-33/ST-2/ILC2 Axis in the Lung Tissue of Type 2 Diabetic Rats
2024, Applied Biochemistry and BiotechnologyAssociation of Lung Fibrotic Changes and Cardiological Dysfunction with Comorbidities in Long COVID-19 Cohort
2023, International Journal of Environmental Research and Public Health