In the present study, we evaluated the long-term association between physical activity and endothelial function in patients with type 2 diabetes and non-diabetic controls. The main findings were that baseline physical activity was significantly lower in patients with type 2 diabetes and associated with endothelial function after 5 years follow-up.
This expands on previous short-term studies evaluating the relationship between exercise and endothelial function. A recent meta-analysis reported improved endothelial function assessed by FMD in patients with type 2 diabetes following exercise interventions.28 Importantly, the studies included in this meta-analysis only evaluated the effect of short-term interventions of typically 8–12 weeks. Prospective data on the long-term effect of physical activity on endothelial function are scarce. However, our results are also in line with two previous long-term observational studies demonstrating a positive association between physical activity and endothelial function in different study populations.29,30 In contrast to our study, these studies relied on self-reported physical activity. In a cohort with a 25-year observation period of healthy middle-aged men, Kwaśniewska et al. found that high levels of self-reported lifetime physical activity were associated with better endothelial function assessed by PAT.29 Pahkala et al. demonstrated that increased self-reported physical activity was associated with improved endothelial function assessed by FMD in adolescents during 5 years of observation.30 Until now, prospective data concerning the long-term association between physical activity and endothelial function assessed by PAT in patients with type 2 diabetes have been lacking.
We found no difference in endothelial function between the two groups. Previous cross-sectional studies have reported diverging results. Lower RHI in diabetes patients were reported in some studies 15–20, whereas other studies reported comparable RHI in patients with versus without diabetes.21–24 Compared to our study population, the studies reporting lower RHI in diabetes patients were characterized by poorer glycemic control (HbA1C = 77 ± 13 mmol/mol)18, longer diabetes duration (14 ± 9 years)19, or a higher proportion of patients with a history of CVD (46%).20 The association with CVD was specifically evaluated in two studies. Lower RHI was reported in patients with type 2 diabetes with CVD compared to non-diabetic subjects without CVD. Conversely, no difference was observed in RHI between patients with diabetes and non-diabetic subjects with CVD.23,24 Likewise, Aragones et al. found comparable levels of RHI in patients with diabetes compared to non-diabetic subjects at intermediate risk of CVD.21 Therefore, a possible explanation for our neutral finding may be that the participants with type 2 diabetes had a short duration of diabetes, were well regulated with regard to glycemia, and, due to more intensive treatment, had fine blood pressure and blood lipid control. Moreover, as previous studies have reported positive effects of both antihypertensives and statins on endothelial function, this may have attenuated potential differences in lnRHI between the groups.36,37 Finally, we found numerically lower LnRHI in patients with type 2 diabetes compared to controls, and the lack of statistical significance could be due to a type II error.
Low levels of physical activity have been associated with increased risk of CVD38, and induction of endothelial dysfunction has been suggested as a causal mechamism.39,40 The beneficial effects of physical activity on endothelial function are thought to be associated with the repeated shear stress stimulation of the vessels during exercise, which leads homeostatic changes with increased nitric oxide bioavailability.41 Ultimately, these changes induce arterial adaptations that may influence the risk of cardiovascular disease.
A limitation to this study is that endothelial function was only assessed after 5 years of follow-up, hence baseline differences or temporal changes in endothelial functions could not be assessed. In addition, a number of participants did not attend the follow-up visit, which could have biased the results. However, baseline characteristics between patients with vs. without follow-up data were comparable and the bias from dropouts and missing data are most likely of little significance. Strengths of the study include a very well characterized study population. Also, the patients with type 2 diabetes were treated according to current guidelines with good risk factor control. Moreover, as opposed to previous prospective studies, physical activity was objectively measured using accelerometery. Thus, the potential for recall bias was not an issue in this regard.