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This study determined the interindividual variation in the cardiometabolic response to 6 months of moderate or vigorous intensity exercise training (ET) among youth at risk for type 2 diabetes mellitus. Youth were randomized to moderate intensity ET (45-55% heart rate reserve; n = 31), vigorous intensity ET (70-85% heart rate reserve; n = 37), or control ( n = 36). Only those attending ≥70% of ET sessions were included. Cardiometabolic measures included insulin sensitivity, hepatic triglyceride content, visceral adipose area, and cardiorespiratory fitness. The contribution of ET to interindividual variation was determined using the standard deviation of individual responses (SD IR ) and considered meaningful if the SD IR surpassed the smallest worthwhile difference (SWD), calculated as 0.2 × the standard deviation of the control group baseline values. ET meaningfully contributed to the interindividual variation among changes in peak oxygen uptake following moderate (SD IR : 2.04) and vigorous (SD IR : 3.43) ET (SWD: 1.17 mL·kg fat free mass -1 ·min -1 ), body fat percentage and hepatic triglyceride content following moderate-intensity ET (SD IR : 1.64, SWD: 1.05%; SD IR : 10.08, SWD: 1.06%, respectively), and visceral fat mass following vigorous ET (SD IR : 11.06, SWD: 7.13 cm 2 ). Variation in the changes in insulin sensitivity were not influenced by ET. The contribution of ET to interindividual variation appears to be influenced by the desired outcome and prescribed intensity. Trial registration at ClinicalTrials.gov (identifier no.: NCT00755547). Novelty: The contribution of exercise to interindividual variation following training depends on the outcome and exercise intensity. Increasing exercise intensity does not systematically reduce non-response among youth at risk for type 2 diabetes.

Sprint interval training (SIT) is reported to improve blood glucose control and may be a useful public health tool. The sirtuins and associated genes are emerging as key players in blood glucose control. This study investigated the interplay between the sirtuin/NAD system and individual variation in insulin sensitivity responses after SIT in young healthy individuals. Before and after 4 weeks of SIT, body mass and fat percentage were measured and oral glucose tolerance tests performed in 20 young healthy participants (7 females). Blood gene expression profiles (all 7 mammalian sirtuin genes and 15 enzymes involved in conversion of tryptophan, bioavailable vitamin B3, and metabolic precursors to NAD). NAD/NADP was measured in whole blood. Significant reductions in body weight and body fat post-SIT were associated with altered lipid profiles, NAD/NADP, and regulation of components of the sirtuin/NAD system (NAMPT, NMNAT1, CD38, and ABCA1). Variable improvements in measured metabolic health parameters were evident and attributed to different responses in males and females, together with marked inter-individual variation in responses of the sirtuin/NAD system to SIT.