Diabetes mellitus type II is a major public health problem with more than 25 million people in Europe affected by the disease [
1]. The disorder results from interactions between genetic, environmental and behavioral factors [
2‐
4]. The latter may be considered a modifiable risk factor and mainly denotes poor health behavior in terms of a high caloric diet and physical inactivity. In view of that, it has been persistently shown that reducing caloric intake and being physically active or performing endurance and strength training on a regular basis to improve physical fitness prevent diabetes mellitus type II development [
5] and ameliorate glycemic control [
6‐
8].
Unaccustomed eccentric exercise (muscle lengthening contraction form) is associated with muscle damage inducing reduced glucose transporter type 4 (GLUT4) levels that seems to be the major reason for transient insulin resistance [
9‐
11]. However, it has been shown that repeated bouts of eccentric exercise are protective against further damage caused by subsequent eccentric sessions [
12,
13]. Furthermore, it was recently reported that eccentric exercise is not only an effective training method to increase muscle strength and endurance, but may also increase glucose tolerance comparable to concentric exercise [
14‐
20]. Eccentric endurance exercise might be implemented by downhill walking/hiking in a hilly or mountainous environment. In contrast to uphill walking which is considered a concentric endurance exercise, downhill walking opposes less strain on the cardiovascular system but a relatively high strain on the contractile units of muscles [
21,
22]. Therefore, downhill walking might be a valuable training modality for persons displaying a low physical fitness and impaired glucose metabolism, as for example subjects suffering from pre-diabetes.
Besides the possibility of mountainous environments to easily perform eccentric endurance exercises, increasing altitude also involves decreasing atmospheric pressure leading to hypobaric hypoxia. While altitudes above 1500 m lead to an altitude-dependent decline of exercise capacity [
23,
24], hypoxia has been shown to improve glucose transport and insulin action [
25‐
27] and furthermore may be a stimulus for increasing exercise performance [
28]. In this regard, research has shown that both eccentric exercise and hypoxia may induce inflammation and increase reactive oxygen species (ROS) [
29‐
33]. High levels of contraction-induced ROS have been associated with muscle damage and impaired muscle function [
34] and acute exercise under hypoxic conditions promotes DNA strand breaks and oxidative DNA damage more than exercise under normoxia [
35]. However, contraction-induced ROS also activates important cell signaling pathways mediating training adaptations such as improved antioxidant capacity [
36], mitochondrial biogenesis [
37‐
39] and hypertrophy [
40]. In fact, it was demonstrated that positive exercise-induced adaptations such as vasodilation [
41], mitochondrial biogenesis [
39,
42] and insulin sensitivity [
43] are blunted when loading cells with high doses of antioxidants or after oral antioxidant treatment. Moreover, exercise-induced ROS production is highly individual and persons producing less exercise-induced oxidative stress exhibited the lowest training adaptations after endurance training [
44‐
46]. It is also known that overweight persons with type II diabetes display higher basal levels of oxidative stress that can be reduced by exercise training, but the link between reduction of basal oxidative stress and improved glucose metabolism has not yet been confirmed [
47,
48]. Additionally, eccentric exercise was reported to increase the antioxidative capacity and thus to be protective against oxidative injury [
49]. Thus, we assumed that eccentric endurance training performed at low or moderate altitude (i.e., 2000–2500 m) might have distinct effects on redox status and could differently impact on physical fitness.
The effects of eccentric exercise training at moderate altitude on exercise performance and redox status in pre-diabetic people are not established yet. Therefore, this study aimed (a) to evaluate the effects of eccentric exercise training at low and moderate altitudes on physical fitness in pre-diabetic men and (b) to establish whether or not oxidative stress levels and antioxidant status are associated with performance improvements. We hypothesized that eccentric exercise training performed at moderate altitude will improve performance more than at low altitude and that redox changes may at least partly explain the expected differences.