title: Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans.
abstract: Glucose tolerance is lower in the evening and at night than in the morning. However, the relative contribution of the circadian system vs. the behavioral cycle (including the sleep/wake and fasting/feeding cycles) is unclear. Furthermore, although shift work is a diabetes risk factor, the separate impact on glucose tolerance of the behavioral cycle, circadian phase, and circadian disruption (i.e., misalignment between the central circadian pacemaker and the behavioral cycle) has not been systematically studied. Here we show--by using two 8-d laboratory protocols--in healthy adults that the circadian system and circadian misalignment have distinct influences on glucose tolerance, both separate from the behavioral cycle. First, postprandial glucose was 17% higher (i.e., lower glucose tolerance) in the biological evening (8:00 PM) than morning (8:00 AM; i.e., a circadian phase effect), independent of the behavioral cycle effect. Second, circadian misalignment itself (12-h behavioral cycle inversion) increased postprandial glucose by 6%. Third, these variations in glucose tolerance appeared to be explained, at least in part, by different mechanisms: during the biological evening by decreased pancreatic β-cell function (27% lower early-phase insulin) and during circadian misalignment presumably by decreased insulin sensitivity (elevated postprandial glucose despite 14% higher late-phase insulin) without change in early-phase insulin. We explored possible contributing factors, including changes in polysomnographic sleep and 24-h hormonal profiles. We demonstrate that the circadian system importantly contributes to the reduced glucose tolerance observed in the evening compared with the morning. Separately, circadian misalignment reduces glucose tolerance, providing a mechanism to help explain the increased diabetes risk in shift workers.
authors: Medical Chronobiology Program, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115; cjmorris@partners.org fscheer@rics.bwh.harvard.edu.
authors: Christopher J
authors: CJ
authors: Morris
authors: Medical Chronobiology Program, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115;
authors: Jessica N
authors: JN
authors: Yang
authors: Medical Chronobiology Program, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115;
authors: Joanna I
authors: JI
authors: Garcia
authors: Medical Chronobiology Program, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115;
authors: Samantha
authors: S
authors: Myers
authors: Medical Chronobiology Program, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115;
authors: Isadora
authors: I
authors: Bozzi
authors: Medical Chronobiology Program, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115;
authors: Wei
authors: W
authors: Wang
authors: Medical Chronobiology Program, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115; Department of Biobehavioral Health, Pennsylvania State University, University Park, PA 16802; and.
authors: Orfeu M
authors: OM
authors: Buxton
authors: Medical Chronobiology Program, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115; Oregon Institute of Occupational Health Sciences, Oregon Health & Science University, Portland, OR 97239.
authors: Steven A
authors: SA
authors: Shea
authors: Medical Chronobiology Program, Division of Sleep and Circadian Disorders, Brigham and Women's Hospital, Boston, MA 02115; Division of Sleep Medicine, Harvard Medical School, Boston, MA 02115; cjmorris@partners.org fscheer@rics.bwh.harvard.edu.
authors: Frank A J L
authors: FA
authors: Scheer
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002940:Circadian Rhythm; D003920:Diabetes Mellitus / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D019518:Postprandial Period; D012890:Sleep
chemical_list: D001786:Blood Glucose
keywords: circadian disruption; diabetes; glucose metabolism; night work; shift work