6MWT and diabetes mellitus
This study was designed to investigate the functional exercise capacity in patients with DM and healthy controls. The findings from this study show that patients with DM demonstrated significantly lower exercise capacity than healthy controls. The 6MWT is widely used to measure the functional status and prognosis in patients with a wide variety of diseases, such as chronic obstructive pulmonary disease (COPD), pulmonary hypertension, and congestive heart failure. This test can also be utilized to investigate the effects of several interventions, for example, rehabilitation, treatment regimen changes, and oxygen supplementation, on patients’ walking capacity. In the literature, there are few papers that assess the use of the 6MWT in diabetic patients. Diabetes belongs to a group of disorders that reduce regular physical capacity [6, 17]. For example, Janevic et al.  found a significant reduction in the distance walked during the walking test in elderly women with diabetes (> 60 years old) with concomitant heart failure. Similar observations were made by other authors [19, 20] for patients with diabetes and congestive heart failure problems. In addition, Ingle et al.  observed a reduction in the distance walked in patients with diabetes and coexistent left ventricular systolic dysfunction (LVSD) during the walking test. Furthermore, these researchers noted that diabetes is an additional factor reducing the distance walked irrespective of coexisting LVSD. The poor exercise capacity in patients with diabetes based on the results of the 6MWT might be because of the link between diabetes and adverse cardiac effects. Thus, low exercise capacity may also have adverse consequences for DM patients during exercise . Impaired exercise capacity is a powerful and independent predictor of an increased risk of cardiac events in DM patients. The reduction in exercise capacity in patients with DM may be linked to poor glucose metabolism. Hyperglycemia directly increases protein glycation and the formation of advanced glycation end products. In this situation, poor glycemic control has been associated with increased stiffness of vessels in the vascular bed in several organs, including the lungs . Compliance plays a significant role in modulating coronary artery blood flow, which has important consequences for myocardial work capacity and, therefore, leads to reduced exercise capacity. A reduction in the distance walked in the walking test was also observed in patients with diabetes and concomitant peripheral circulatory insufficiency [24, 25]. Another important aspect of long-term diabetic complications is the involvement of the autonomic nervous system in almost every organ, including the lungs. Diabetic neuropathy can involve the entire autonomic nervous system—the vasomotor, visceromotor and sensory fibers innervating each organ. It has been shown that dysfunction of the cholinergic system  and adrenergic denervation  are significant parts of the clinical picture of diabetic neuropathy. In 2010, van Stolen et al.  published a paper assessing the influence of diabetic neuropathy on daily physical capacity. In the cohort of 100 people with type 2 diabetes, 40 people suffered from diabetic neuropathy, while obesity was present in 53 individuals (BMI > 30 kg/m2). The average 6MWD in the people with diabetes was 537 (SD 89) m. Daily activity was assessed by measuring the number of steps walked. The people with diabetes took 6500 steps a day, which was much fewer than recommended. It is believed that daily activity should amount to 10,000 steps per day . Peripheral neuropathy and obesity were strictly related to the reduction in physical capacity in people with diabetes.
In this study, the groups varied in terms of the distance walked. The diabetic patients had poorer tolerance of physical exercise than the healthy controls. On average, the patients with diabetes covered a distance more than 109 m shorter than that covered by individuals in the CG. Importantly, a change of 30 m or more is considered a clinically important difference . The difference in the 6MWT distance between the two groups can be partially explained by the fact that the patients with diabetes were significantly older, with a higher body weight and BMI, and showed micro- and macroangiopathic complications of diabetes. The number of diabetic complications was similar in both subgroups. The conditions for the 6MWT are similar to natural conditions in which a physical workload is present. In this study, the walking test was shown to be very useful in diversifying both groups (CG and DM) and determining daily physical capacity in the DM group. The usability of the 6MWT results from its direct significant connection with stress, heart rate, blood oxygen saturation and exertional dyspnea compared with the connection between these parameters and exercise tests on a cycle ergometer or treadmill in middle-aged adults [30, 31] and in elderly people . It was also found that in elderly people of ages ≥68, the 6MWT correlates well with many characteristics and concomitant disorders . The factors that significantly influenced the reduction in the 6MWT distance in both sexes included old age; higher body weight and abdominal circumference; lower muscle strength; the presence of depressive syndromes, joint diseases, coronary heart disease, stroke, or diabetes; lower education level; non-Caucasian race; angiotensin-converting enzyme inhibitor use; higher concentrations of fibrinogen; and higher white blood cell (WBC) count . In women, a reduction in the 6MWT distance was also associated with low values of FEV1, diastolic blood pressure, and increased CRP concentration. Furthermore, the intake of digitalis resulted in a worsening of the results in men.
Pulmonary function tests and diabetes mellitus
Pulmonary complications in diabetes attract the attention of researchers from various clinical disciplines, including an increasing number of pulmonologists. However, despite the regular updating of the relatively extensive literature with new scientific reports, pulmonary complications in diabetes remain difficult to explain. The lungs are a target organ for damage in diabetes, in which the transfer capacity of CO is decreased. The results of previous studies demonstrate that diabetes is independently associated with a clinically significant burden of respiratory symptoms and a reduction in lung function. The impact of diabetes on the lungs is confirmed by histopathologic examinations of the lung parenchyma and pulmonary function testing of the respiratory tract [34,35,36]. The studies show variations in the results obtained from spirometry, body plethysmography and the test of the diffusing capacity for carbon monoxide, which impedes a clear interpretation of the obtained results . Moreover, most functional studies of the respiratory tract include nonsmokers without concomitant pulmonary disorders. On the other hand, concomitant obesity, tobacco smoking, heart failure and disorders related to diabetes can significantly influence the reduction in pulmonary function in patients with diabetes, especially those with type 2 diabetes mellitus . However, no commonly acceptable and reproducible methods to identify and monitor pulmonary angiopathy have been introduced so far. One of the reasons for this reduction in pulmonary function may be the vascular and capacitive reserve of the lung parenchyma. This reserve compensates for the partial loss of ventilation and vascular reserves of the pulmonary circulation in the course of diabetes. Attempts to introduce inhalatory insulin for general use may provide further incentive for research on the course of pulmonary microangiopathy caused by chronic hyperglycemia [39, 40].
An interesting aspect of this study is the close concomitance of the lack of correction of metabolic parameters (HBA1c), the increase in biochemical parameters of chronic inflammation (CRP and fibrinogen) and the impairment of respiratory mechanics in diabetic patients. Compared with the CG, the patients with diabetes showed significant impairment of respiratory mechanics [VC (P < 0.05), FEV1 (P < 0.001), TLC (P < 0.05), DLCO (P < 0.001)].
It was also found that diabetes clearly influences the decrease in the strength and resistance of respiratory muscles, primarily the diaphragm . The disorder also adversely affects the structure of collagen in the lung parenchyma and cartilage in the chest wall [42, 43]. These changes lead to the reduction in chest mobility  and thus to an additional deficiency in breathing mechanics. This progression suggests the systemic influence of diabetes, particularly on the respiratory system and indirectly on the physical capacity of these patients.
The present findings must be interpreted with caution because of some methodological limitations. One important limitation was the limited sample size. Another potential limitation of our study could be the presence of a number of existing underlying pathologies, such as cardiovascular disease, and a previous history of physical inactivity and an unhealthy lifestyle, which contribute to a low functional exercise capacity. Another caveat is that people with type 1 and type 2 diabetes were coanalyzed. However, both type 1 and type 2 diabetes have been associated with microangiopathy and macroangiopathy. The observations in this study included only diabetic patients who had never smoked and did not have coexisting chronic respiratory disorders. The influence of smoking and respiratory diseases can be additional factors adversely affecting the functional status of the respiratory system. Passive smoking has not been studied, despite its adverse effects on exercise capacity. One of the major limitations of 6MWT is the lack of adequate information on the mechanism and cause of disability during exercise. The distance walked in the 6MWT may vary according to the patient’s motivation or other individual factors. It should be noted that there are other factors affecting the result of the 6MWT: the patient’s motivation to exercise, leg length, and level of physical activity. Therefore, further studies with a larger sample size and a variable profile of diabetic subjects are recommended.