The current study indicated a significant increase in VO2peak, exercise time, and improvement of BMI and HRmax in three training groups. It has been found that T2DM patients have lower cardiorespiratory fitness (CRF) in contrast to healthy individuals (22, 23). Previous research has indicated that HIIT results in more significant CRF improvements than traditional training at lower intensities among individuals with chronic diseases such as metabolic syndrome (24, 25). It has been considered that the lower level of CRF shown in T2DM might be associated with low capillary density, increased blood viscosity, higher blood glucose levels, and presence of neuropathic and vascular complications in T2DM (26), besides plays as a significant predictor for cardiovascular mortality. However, T2DM patients shown lower CRF, exercise training intervention can ameliorate CRF and decrease cardiovascular mortality. In that respect, as every 3.5 mL/min/kg increment of VO2max has been shown to a 12% improvement in survival (27).
Moreover, studies have found that exercise intensity plays an essential factor in CRF improvements (24). Studies have emphasized the potent efficacy of HIIT on CRF, with more significant advantages than other exercise training types in T2DM patients. Støa et al. demonstrated three months of HIIT training contain 4×4 min with 85–95% of HRmax improved VO2max and BMI in T2DM (22). Furthermore, Hansen et al. also were found 16% (75% VOpeak) and 8% (50% VOpeak) improvements in VO2max following two months (28). In the current study, the more remarkable improvement of VO2peak, exercise time, and BMI decrease were found in the combined training group. Recent reviews recommend that HIIT interventions, short and medium-term, are an efficient stimulus to improve CRF and body composition characters in individuals with T2DM (29). It seems that mechanisms involved in the superiority of HIIT, despite mode, maybe due to creating a more significant challenge to the heart, changes in the stroke volume induced by an increment of cardiac contractility (30), and skeletal muscle oxidative capacity, which improves mitochondrial function (24), thus increasing CRF. Enhancing of VO2peak has been related to improved glycemic control, insulin-stimulated glucose uptake rate (31), and blood pressure in T2DM individuals (17).
Moreover, we demonstrated a decrement of TG, TC, and LDL and an increase in HDL after 12 weeks of intervention in all training groups. There was a significant difference in HDL and LDL concentration among three training groups with the CON group. Besides, significant differences have been found between ST with HIIT and HIIT + ST groups in HDL and LDL values. Moreover, due to training, DBP and SBP decreased in experimental groups, but only HIIT + ST a substantial decrement in SBP following 12 weeks of intervention. Exercise training has heterogeneous effects on lipid profile and blood pressure. Although these results are in line with prior investigations, which found only the HIIT with RT group improved TC and LDL-C compared to the control group (32). In another study, improvements for TG, HDL, and SBP has been found following the HIIT intervention (8). Similarly, Mitranum et al. showed that HIIT training improved LDL, HDL, TG, and SBP, although the changes were associated with the pre-intervention values (17). Previous researches also described decreases in blood pressure phenomena. Jorge et al. demonstrated that combined training (aerobic, resistance) significantly decreased blood pressure (33).
Additionally, a significant reduction in SBP has been shown after resistance training in T2DM patients (34). However, another study did not find any blood pressure reductions after exercise training (35). It seems that the lack of significant differences in blood pressure, TC, and TG among the groups in the current study was likely due to the absence of significant differences in weight loss, as hypothesized by previous researches (33, 35).
In glycemic status, HOMA-IR, HbA1c, insulin and, fasting plasma glucose had improved significantly in HIIT, ST, and HIIT + ST groups, with no differences among the four groups. HbA1c is a long-term indication of glycemic status that is substantially attenuated following HIIT training, despite mode. Previous researches have studied the effect of HIIT on %HbA1c in a patient with T2DM. In that respect, T2DM patients who carry out a HIIT program with 85–95% of HRmax showed a significant reduction in HbA1c compared to moderate-intensity continuous training, though insulin was not changed significantly (22). Karstoft et al. found more significant improvements in glycemic control in HIIT compared to the continuous-walking training in T2DM patients (36). A recent meta-analysis illustrated that HIIT is more efficient than moderate-intensity continuous training for improving insulin sensitivity in healthy individuals (37). It has been demonstrated that each 1% reduction in HbA1c levels was related by a 14% decrease of myocardial infarctions and a 21% reduction of risk of-death associated with diabetes (38).
Moreover, we demonstrate that insulin and HOMA-IR, known as insulin resistance, significantly decreased in all experimental groups. In insulin resistance (IR), the biological function of insulin is decreased in peripheral target tissues. IR resulted in a disproportionate insulin value to the glycemic level. Thus, IR is associated with a hyperinsulinemia status (39). The present results tend to be in line with previous observations, where a cohort study demonstrated significantly improved IR (~ 15%) and metabolic markers after 4-month strength training (70–80% 1RM) on diabetic subjects (40). Additionally, ST (more than 85% 1RM) resulted in ameliorating insulin sensitivity in people with diabetes, while the effect of endurance training was moderate (41).
Moreover, in T2DM patients, insulin levels were substantially decreased following chronic HIIT performed by walking exercise (42). HIIT significantly attenuates FPG in T2DM patients (43, 44), similar to the current study. Winding et al. performed 33 sessions of cycle-ergometer HIIT and reported lower fasting plasma glucose (44). Moreover, 16 weeks of HIIT (jogging/running) decreased fasting plasma glucose in adults with T2DM (43). Despite the lack of differences among groups, these results emphasize the HIIT as an effective strategy to produce significant effects on glycemic status in T2DM patients. The mechanisms for ameliorated glycemic status related to exercise training are not completely clear. Improved glycemic control induced by HIIT seems to be associated by the increment of insulin signaling, insulin-stimulated glucose disposal rates, glucose transporter protein levels, and improved skeletal muscle blood flow, enhancing the glucose delivery (45), and local factors related with exercise training (15). Although all of these processes seem intensity-dependent, theoretically HIIT appears to be more effective (46).
Previous research has presented a significant association among inflammation and oxidative stress that could be referred to as the oxidative-inflammatory cascade (OIC) in T2DM. On the other hand, the anti-inflammatory and oxidative stress effect of exercise has been discussed recently. In the current study, we demonstrated that the overall concentration of SOD, GPx, MDA, TAC, TNF-α, IL-6, and CRP significantly improved in 3 experimental groups, besides, TNF-α and SOD concentration showed significant reduction and increased in the CON group, respectively. In this regard, Mohammadi Zadeh at al. demonstrated that HIIT decrement pro-inflammatory parameters and improved anti-inflammatory factors in T2DM people (47). Khanna et al. (2017) shown that combined exercise (aerobic + resistance) has more effects on decrement of TNF-α, CRP, IL-1β and, IL-6 compared to aerobic or resistance training alone (48). In our investigation, the combined training group showed greater improvement in inflammation factors comparison to the others. Similar results to the ones in our study were presented with decreased CRP levels while using a different protocol of HIIT, either alone or combined with RT in T2DM patients (9).
Moreover, two short types of research reporting no substantial effects on IL-6, TNF-α, and CRP in T2DM (49). Moreover, in a meta-analysis with T2DM individuals, aerobic exercise was related to reducing CRP, while strength or combined training was not (50). According to the previous investigation, it seems that weight loss is required to moderate such factors (51). Inflammatory cytokines, including TNF-α and CRP, were leading to decreased insulin sensitivity and the evolution of diabetic complications (7). The exact mechanism of the anti-inflammatory effect of HIIT is not precise. However, the reduction of visceral fat mass and muscular anti-inflammatory myokines production, such as IL-6 (52), has been proposed to improve inflammatory status after an exercise intervention.
Furthermore, pro-inflammatory factors resulting from the IR state induce increment in ROS and free radicals and induce more significant oxidative stress in T2DM (53). On the other hand, the exposure to pro-oxidant inducers such as HIIT increases antioxidant capacity (19). In the current investigation, three HIIT types increase significantly antioxidant enzymes and decreased the MDA levels, with no differences between the groups. A similar study in T2DM subjects demonstrated the different modes of training (strength training, aerobic training, and combined training) provided significant increases in antioxidant enzymes, which may have attenuated oxidative stress of diabetes (54). In the study by Mitranun et al., increases in GPx were reported along with decreases in MDA after the HIIT training, but not traditional exercise training (17). Moreover, HIIT training was able to upregulate antioxidant capacity while continuous training did not suggest a superior effect of HIIT when performed in the long term (49). The impact of long-period exercise training on oxidative stress in T2DM patients has not been thoroughly examined. It has been reported that exercise duration and intensity play an essential role in enhancing the antioxidant defense system (55). In this regard, HIIT activates an activated protein kinase that is significantly associated with cellular energy homeostasis and induces the expression of peroxisome proliferator-activated receptor coactivator-1α (PGC-1α). PGC-1α works as a regulator of mitochondrial biogenesis and helping to improve the VO2max and less oxidative stress (56).