AB Physical activity has been hypothesized to cause adverse metabolic responses in a minority of participants. We use secondary analysis of a randomized controlled trial to investigate rates of adverse metabolic responses in a population at high risk of type 2 diabetes. Methods: We investigated data from the PREPARE trial; individuals with impaired glucose tolerance were randomized to the following: control (advice leaflet); intervention 1, a 3-h group-based structured education program aimed at promoting physical activity; or intervention 2, a 3-h structured education program with personalized pedometer use. Intervention 2, but not intervention 1, resulted in increased physical activity at 3, 6, and 12 months. An adverse response was defined as a change of >=0.8 mmol[middle dot]L-1 for fasting glucose, >=1.3 mmol[middle dot]L-1 for 2-h glucose, >=0.42 mmol[middle dot]L-1 for triglycerides, and -0.12 mmol[middle dot]L-1 or less for HDL-cholesterol. Each group included 29 participants. Data were collected between 2006 and 2008 and analyzed in 2013. Results: In total, 12 (41%) participants in intervention 2 had an adverse response; rates in intervention 1 and the control group were 23 (79%) and 22 (76%), respectively. The odds of an adverse response were reduced in intervention 2 compared with control (OR, 0.22; 95% CI, 0.07-0.69). For the combined cohort, those who had increased physical activity at each time point had reduced odds of an adverse response compared with those who did not (OR, 0.30; 95% CI, 0.10-0.93). Conclusion: Although some individuals experienced an adverse metabolic response after a successful physical activity intervention, rates were higher under control conditions. This study does not support the hypothesis that increased physical activity per se increases the risk of an adverse metabolic response
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