Letter to the editor

One of the hallmarks of health is the integrity of barriers at the cellular and tissue levels. The two cardinal functions of barriers include preventing access of deleterious elements of the environment (barrier function) while facilitating the transport of essential ions, signaling molecules and nutrients needed to maintain the internal milieu (transport function). There are several cellular and subcellular barriers and some of these barriers can be interrelated. The principal physiologic barriers include blood-retinal barrier, blood-brain barrier, blood-testis barrier, renal glomerular/tubular barrier, intestinal barrier, pulmonary blood-alveolar barrier, blood-placental barrier and skin barrier. Tissue specific barriers are the result of the vasculature, cellular composition of the tissue and extracellular matrix within the tissue. Uncontrolled diabetes and acute hyperglycemia may disrupt the integrity of physiologic barriers, primarily through altering the vascular integrity of the tissues and may well contribute to the clinically recognized complications of diabetes. Although diabetes is a systemic disease, some of the organs display clinically significant deterioration in function while others undergo subclinical changes. The pathophysiology of the disruption of these barriers is not entirely clear but it may be related to diabetes-related cellular stress. Understanding the mechanisms of diabetes related dysfunction of various physiologic barriers might help identifying novel therapeutic targets for reducing clinically significant complications of diabetes.

Melatonin is a key intracellular neuroimmune-endocrine regulator and coordinator of multiple complex and interrelated biological processes. The main functions of melatonin include the regulation of neuroendocrine and antioxidant system activity, blood pressure, rhythms of the sleep-wake cycle, the retardation of ageing processes, as well as reseting and optimizing mitochondria and thereby the cells of the immune system. Melatonin and its agonists have therefore been mooted as a treatment option across a wide array of medical disorders. This article reviews the role of melatonin in the regulation of respiratory system functions under normal and pathological conditions. Melatonin can normalize the structural and functional organization of damaged lung tissues, by a number of mechanisms, including the regulation of signaling molecules, oxidant status, lipid raft function, optimized mitochondrial function and reseting of the immune response over the circadian rhythm. Consequently, melatonin has potential clinical utility for bronchial asthma, chronic obstructive pulmonary disease, lung cancer, lung vascular diseases, as well as pulmonary and viral infections. The integration of melatonin's effects with the alpha 7 nicotinic receptor and the aryl hydrocarbon receptor in the regulation of mitochondrial function are proposed as a wider framework for understanding the role of melatonin across a wide array of diverse pulmonary disorders.

To assess the impact of diabetes on restrictive and obstructive lung function impairment.

This 5-year prospective study included 7524 participants aged 40–69 years without lung function impairment at baseline who underwent a comprehensive medical check-up between April 2008 and March 2009 at Saku Central Hospital. Diabetes was defined by fasting plasma glucose ≥ 7.0 mmol/l (126 mg/dl), HbA1c ≥ 6.5% (48 mmol/mol), or a history of diabetes, as determined by interviews conducted by the physicians. Restrictive and obstructive lung function impairment were defined as forced vital capacity (FVC) < 80% predicted and forced expiratory volume in 1 s (FEV₁) to FVC ratio (FEV₁/FVC) < 0.70, respectively. Participants were screened until they developed restrictive or obstructive lung function impairment or until March 2014.

During the follow-up period, 171 and 639 individuals developed restrictive and obstructive lung function impairment, respectively. Individuals with diabetes had a 1.6-fold higher risk of restrictive lung function impairment than those without diabetes after adjusting for sex, age, height, abdominal obesity, smoking status, exercise habits, systolic blood pressure, HDL-cholesterol, log-transformed high-sensitivity C-reactive protein, and baseline lung function [multivariable-adjusted HR and 95% CI; 1.57 (1.04–2.36)]. In contrast, individuals with diabetes did not have a significantly higher risk of obstructive lung function impairment [multivariable-adjusted HR and 95% CI; 0.93 (0.72–1.21)].

Diabetes was associated with restrictive lung function impairment but not obstructive lung function impairment.

Cross-sectional studies have noted that subjects with diabetes have lower lung function than non-diabetic subjects. We conducted this analysis to determine whether diabetic subjects have different rates of lung function change compared with non-diabetic subjects.

We conducted a nested case-control analysis in 352 men who developed diabetes and 352 non-diabetic subjects in a longitudinal observational study of aging in men. We assessed lung function among cases and controls at three time points: Time0, prior to meeting the definition of diabetes; Time1, the point when the definition of diabetes was met; and Time2, the most recent follow-up exam.

Cases had lower forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) at all time points, even with adjustment for age, height, weight, and smoking. In multiple linear regression models adjusting for relevant covariates, there were no differences in rates of FEV₁ or FVC change over time between cases and controls.

Men who are predisposed to develop diabetes have decreased lung function many years prior to the diagnosis, compared with men who do not develop diabetes. This decrement in lung function remains after the development of diabetes. We postulate that mechanisms involved in the insulin resistant state contribute to the diminished lung function observed in our subjects.

To determine whether diabetes is associated with reduced lung function, we studied 421 Anglo-Celt/European subjects, representing 20.5% of all patients with type 2 diabetes identified in an urban Australian catchment area of 120 097 people. In addition to collection of detailed demographic and diabetes-specific data, spirometry was performed and forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), vital capacity (VC) and peak expiratory flow (PEF) measured. When expressed as a percentage of those predicted (%pred) for age, sex and height, the means of all spirometric measures were reduced by ≥9.5%. After controlling for smoking, age and gender in a linear regression model, HbA_1c was not associated with any measure of lung function (P>0.13) but diabetes duration was significantly associated with FEV1_%pred and PEF_%pred (P≤0.04) and had borderline associations with FVC_%pred and VC_%pred (P≤0.064). In separate analyses controlling for smoking alone, age, body mass index (BMI), coronary heart disease (CHD) and retinopathy were independently and inversely associated with FVC_%pred, FEV1_%pred and VC_%pred (P<0.05). In sub-group analyses, these three spirometric measures were associated with BMI, CHD and diabetes duration in males, and age and BMI in females. Pulmonary function is reduced in type 2 diabetes. Diabetes duration seems a more important influence than glycaemic control, but obesity and vascular disease may also contribute.