The metabolic effects of high-intensity interval training combining rowing and cycling in obesity and type 2 diabetes

Insulin resistance is a known characteristic of type 2 diabetes (T2D), which is associated with an increased risk of cardiovascular disease (CVD). Insulin resistant conditions require an increased insulin secretion from the pancreatic beta-cells to maintain glucose homeostasis, and if the betacells fails to compensate for the insulin resistance, hyperglycemia and hence T2D appears. Exercise training is recommended as an essential part of the management of T2D. The effects of regular endurance training at moderate intensity on insulin sensitivity, cardiorespiratory fitness and glycemic control in patients with T2D are well documented, and there seem to be evidence of an effect of endurance training on beta-cell function adjusted for insulin sensitivity in individuals with T2D. Furthermore, regular endurance training improves body composition, and it might be associated with improved markers of systemic low-grade inflammation and adipose tissue (AT) dysfunction. The beneficial effects of exercise training may be mediated through alterations in circulating exerkines, which are released in response to muscle contraction and may exert their effects on other organs and/or within the skeletal muscle. However, although the beneficial metabolic effects of regular exercise training is well documented, it remains to be clarified which mode of exercise training that is most appropriate, both when it comes to the metabolic health effect and to maintaining the training and avoiding injuries. Furthermore, little is known of the effects of regular exercise training on circulating exerkines.

In this thesis, we tested the hypothesis that a novel high-intensity interval training (HIIT) protocol recruiting muscle groups on both upper and lower body would induce marked effects on insulin sensitivity, lipid- and glucose metabolism, VO2max, body composition, glycemic control and beta-cell function and that some of these metabolic responses would be attenuated in individuals with T2D and perhaps in obese glucose-tolerant individuals compared to lean. Furthermore, we tested the hypothesis that the HIIT-protocol would improve AT-derived markers of systemic lowgrade inflammation, and induce reductions in selected exerkines, which are often elevated in sedentary individuals with obesity and T2D.

Sedentary obese men with T2D (n=15) matched with both obese (n=15) and lean (n=18) glucose-tolerant men were enrolled in order to complete 8-weeks of supervised HIIT combining rowing and cycling (3 sessions per week). Before and after the HIIT-intervention, we evaluated insulin sensitivity and beta-cell function by the Botnia clamp (hyperinsulinemic-euglycemic clamp 78 and intravenous glucose tolerance test) combined with indirect calorimetry, and furthermore, VO2max and body composition were evaluated by an incremental exercise test and a DXA-scan. Blood samples, taken on the clamp days, were analyzed for Hb1Ac, blood lipids and AT-derived markers of systemic low-grade inflammation as well as selected exerkines

The HIIT-protocol induced a marked increase in insulin sensitivity by ~42% in men with T2D and by ~27-29% in obese and lean glucose-tolerant men, as well as increases in VO2max, lean body mass and reductions in fat mass in all three groups. Importantly, after the HIIT-protocol, men with T2D achieved a level of insulin sensitivity, which was similar with the level in lean and obese glucosetolerant men at inclusion in the study. Moreover, the HIIT-protocol induced a clinically relevant reduction in Hb1Ac by 4 mmol/mol in men with T2D, and it induced a marked increase in beta-cell function adjusted for insulin sensitivity in men with T2D and to a lesser extent in obese and lean glucose-tolerant men. However, beta-cell function adjusted for insulin sensitivity remained severely impaired in men with T2D post-training compared to the control groups. We observed a high adherence to both training sessions and training intensity as well as no injuries, and interestingly, the HIIT-induced metabolic responses were all intact in obese men with or without T2D. The marked HIIT-induced increase in insulin sensitivity and improvements in body composition were not accompanied by overall improvements in circulating levels of the selected exerkines (IL-6, GDF15, FGF21 or ANGPTL4) in obese men with or without T2D or consistent improvements in classical ATderived markers of systematic low-grade inflammation (leptin, adiponectin and IL-6).

In conclusion, we demonstrated that a novel HIIT-protocol combining rowing and cycling is a well-tolerated and promising mode of exercise training in sedentary individuals with obesity and T2D. Surprisingly, the numerous metabolic improvements in response to the HIIT-protocol did not lead to consistent improvements in the AT-derived markers of systemic low-grade inflammation and it did not overall reduce the level of selected exerkines in obesity or T2D.