0042 The Influence of Obesity and Circadian Timing on Human Glucose Regulation. (27th April 2018)

• Record Type: Journal Article
• Authors: McHill, A W; Thosar, S S; Bowles, N P; Berman, A M; Herzig, M X; Clemons, N A; Morimoto, M; Butler, M P; Emens, J S; Purnell, J Q; Shea, S A
• Is Part Of: Sleep. Volume 41(2018)Supplement 1
• Page Start: A17
• Page End: A18
• Publication Date: 2018-04-27
• Subjects: Sleep -- Physiological aspects -- Periodicals; Sleep disorders -- Periodicals; Sommeil -- Aspect physiologique -- Périodiques; Sommeil, Troubles du -- Périodiques; Sleep disorders; Sleep -- Physiological aspects; Sleep -- physiological aspects; Sleep Wake Disorders; Psychophysiology; Electronic journals; Periodicals; 616.8498
• DOI: 10.1093/sleep/zsy061.041
• Languages: English
• ISSNs: 0161-8105

Abstract

Abstract: Introduction: The influence of circadian timing on glucose regulation has been well-studied in normal-weight humans, but is poorly understood in obese individuals. We therefore sought to test whether obesity influenced the relationships between circadian timing and pre/post-prandial glucose and insulin responses. Methods: After 1–3 weeks of maintaining a consistent 8h sleep schedule at habitual timing, 17 participants (10-female), aged 50 ± 6 years, 7 obese (BMI >30kg/m 2 ), underwent a 5-day inpatient forced desynchrony protocol in dim-lighting (<4lux) and free of other time cues. The protocol consisted of ten 5h 20min 'days' where all behaviors and meals were scheduled identically. For each wake episode, plasma insulin and glucose levels were assessed upon awakening and at the same time following each identical meal. Circadian phase for each measurement was determined relative to the salivary dim-light melatonin onset (>3pg/mL threshold). Data were analyzed using a mixed-effect model with group (obese vs. non-obese) and circadian phase as fixed factors, subject as a random factor, and apnea-hypopnea index as a covariate. Cosinor analyses were performed to determine circadian acrophase timing. Results: There was an endogenous circadian rhythm in pre-meal glucose levels upon awakening, with the peak in the obese group occurring ~3h earlier (~7am) than the non-obese group (p<0.01). Awakening insulin levels exhibited a trend (p=0.05) for an interaction between obesity and circadian phase. Postprandial glucose also followed a circadian rhythm in both groups (p<0.001), with a nadir in the morning and a peak in the evening. Postprandial insulin was higher in the obese group across all circadian phases (p<0.05). Conclusion: These data suggest that the circadian system affects glucose metabolism and that obesity appears to alter this circadian effect on glucose regulation (the obese group reaching highest awakening glucose levels in the morning hours). The mechanisms remain to be elucidated and could include circadian effects on glucose absorption, peripheral adipocyte insulin sensitivity, or hepatic glucose production. These findings may have implications for diagnosis or treatment of impaired glucose tolerance. Support (If Any): NIH R01-HL125893, KL2TR002370-01, F32-HL131308, MRF of Oregon, Ford Foundation, and CTSA grant (UL1TR000128).