Mathijs Drummen1, Lea Tischmann1, Blandine Gatta-Cherifi2, Anne Raben3, Tanja Adam1, Margriet S Westerterp-Plantenga4. 1. Department of Nutrition and Movement Sciences, NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 MD, Maastricht, the Netherlands. 2. Department of Endocrinology, Diabetology and Nutrition, Universite de Bordeaux, Bordeaux, France. 3. Department of Nutrition, Exercise and Sports, University of Copenhagen, and Steno Diabetes Center, Copenhagen, Denmark. 4. Department of Nutrition and Movement Sciences, NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 MD, Maastricht, the Netherlands. m.westerterp@maastrichtuniversity.nl.
Abstract
BACKGROUND: Circadian rhythm is altered in individuals with obesity and insulin resistance, showing a smaller amplitude, less stability, and increased intradaily variation. OBJECTIVE: We compared reproducibility of circadian-rhythm parameters over time and under free-living vs. controlled conditions in participants with obesity and pre-diabetes after 2- and 3-year weight-loss maintenance during the 3-year PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and around the World) study. Associations of obesity and insulin resistance with circadian-rhythm parameters were assessed. SUBJECTS AND METHODS: Circadian-rhythm parameters were determined using continuous wrist-temperature measurements in free-living environments at year 2 (n = 24; age 56.8 ± 10.3 y; body mass index (BMI) = 30 ± 3.9 kg/m2; homeostatic model assessment of insulin resistance (HOMA-IR) 2.4 ± 1.1), at year 3 (n = 97; age 61.7 ± 7.8; BMI = 29.7 ± 3.9; HOMA-IR 2.9 ± 2.1), and at year 3 in a controlled condition (n = 38; age 63.4 ± 6.7; BMI = 28.7 ± 3.9; HOMA-IR 3.8 ± 1.4). Reproducibility was assessed by analyzing repeatability coefficients (CR), differences, and associations, over time as well as between conditions. Associations of BMI and HOMA-IR with circadian-rhythm parameters were assessed at y-3 in both conditions using factor analysis, followed by Pearson's correlations. RESULTS: Reproducibility of circadian-rhythm parameters over time in the free-living environments was high (CR 0.002-5.26; no significant differences; associated amplitudes r = 0.57; p < 0.01). In contrast, reproducibility between different conditions was low (CR 0.02-11.36; significant differences between most parameters (p < 0.05); yet associated amplitudes r = 0.59; p < 0.01). In the controlled vs. free-living condition circadian-rhythm was more stable; BMI and HOMA-IR were associated with the physiological amplitude-related parameters (r = -0.45; p < 0.01; r = -0.33; p < 0.05). In the free-living environment, BMI and behavioral circadian-rhythm parameters indicating circadian alignment, contributed most to the explained variation (47.1%), and were inversely associated (r = -0.22; p < 0.05), while HOMA-IR was inversely associated with stability-related circadian-rhythm parameters (r = -0.21; p < 0.05). CONCLUSIONS: Circadian rhythm was highly reproducible over time in the free-living environments, yet different under different conditions, being more stable in the controlled condition. BMI may play a significant role in circadian alignment and vice versa in the free-living environment.
BACKGROUND: Circadian rhythm is altered in individuals with obesity and insulin resistance, showing a smaller amplitude, less stability, and increased intradaily variation. OBJECTIVE: We compared reproducibility of circadian-rhythm parameters over time and under free-living vs. controlled conditions in participants with obesity and pre-diabetes after 2- and 3-year weight-loss maintenance during the 3-year PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and around the World) study. Associations of obesity and insulin resistance with circadian-rhythm parameters were assessed. SUBJECTS AND METHODS: Circadian-rhythm parameters were determined using continuous wrist-temperature measurements in free-living environments at year 2 (n = 24; age 56.8 ± 10.3 y; body mass index (BMI) = 30 ± 3.9 kg/m2; homeostatic model assessment of insulin resistance (HOMA-IR) 2.4 ± 1.1), at year 3 (n = 97; age 61.7 ± 7.8; BMI = 29.7 ± 3.9; HOMA-IR 2.9 ± 2.1), and at year 3 in a controlled condition (n = 38; age 63.4 ± 6.7; BMI = 28.7 ± 3.9; HOMA-IR 3.8 ± 1.4). Reproducibility was assessed by analyzing repeatability coefficients (CR), differences, and associations, over time as well as between conditions. Associations of BMI and HOMA-IR with circadian-rhythm parameters were assessed at y-3 in both conditions using factor analysis, followed by Pearson's correlations. RESULTS: Reproducibility of circadian-rhythm parameters over time in the free-living environments was high (CR 0.002-5.26; no significant differences; associated amplitudes r = 0.57; p < 0.01). In contrast, reproducibility between different conditions was low (CR 0.02-11.36; significant differences between most parameters (p < 0.05); yet associated amplitudes r = 0.59; p < 0.01). In the controlled vs. free-living condition circadian-rhythm was more stable; BMI and HOMA-IR were associated with the physiological amplitude-related parameters (r = -0.45; p < 0.01; r = -0.33; p < 0.05). In the free-living environment, BMI and behavioral circadian-rhythm parameters indicating circadian alignment, contributed most to the explained variation (47.1%), and were inversely associated (r = -0.22; p < 0.05), while HOMA-IR was inversely associated with stability-related circadian-rhythm parameters (r = -0.21; p < 0.05). CONCLUSIONS: Circadian rhythm was highly reproducible over time in the free-living environments, yet different under different conditions, being more stable in the controlled condition. BMI may play a significant role in circadian alignment and vice versa in the free-living environment.
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