title: Effects of the Internal Circadian System and Circadian Misalignment on Glucose Tolerance in Chronic Shift Workers.
abstract: BACKGROUND
  Shift work is a risk factor for diabetes. The separate effects of the endogenous circadian system and circadian misalignment (ie, misalignment between the central circadian pacemaker and 24-hour environmental/behavioral rhythms such as the light/dark and feeding/fasting cycles) on glucose tolerance in shift workers are unknown.
  
  
  OBJECTIVE
  The objective of the study was to test the hypothesis that the endogenous circadian system and circadian misalignment separately affect glucose tolerance in shift workers, both independently from behavioral cycle effects.
  
  
  METHODS
  A randomized, crossover study with two 3-day laboratory visits.
  
  
  METHODS
  Center for Clinical Investigation at Brigham and Women's Hospital.
  
  
  METHODS
  Healthy chronic shift workers.
  
  
  METHODS
  The intervention included simulated night work comprised of 12-hour inverted behavioral and environmental cycles (circadian misalignment) or simulated day work (circadian alignment).
  
  
  METHODS
  Postprandial glucose and insulin responses to identical meals given at 8:00 am and 8:00 pm in both protocols.
  
  
  RESULTS
  Postprandial glucose was 6.5% higher at 8:00 pm than 8:00 am (circadian phase effect), independent of behavioral effects (P = .0041). Circadian misalignment increased postprandial glucose by 5.6%, independent of behavioral and circadian effects (P = .0042). These variations in glucose tolerance appeared to be explained, at least in part, by different insulin mechanisms: during the biological evening by decreased pancreatic β-cell function (18% lower early and late phase insulin; both P ≤ .011) and during circadian misalignment presumably by decreased insulin sensitivity (elevated postprandial glucose despite 10% higher late phase insulin; P = .015) without change in early-phase insulin (P = .38).
  
  
  CONCLUSIONS
  Internal circadian time affects glucose tolerance in shift workers. Separately, circadian misalignment reduces glucose tolerance in shift workers, providing a mechanism to help explain the increased diabetes risk in shift workers.
authors.affiliation: Medical Chronobiology Program (C.J.M., T.E.P., J.M., F.A.J.L.S.), Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts 02115; and Division of Sleep Medicine (C.J.M., F.A.J.L.S.), Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Morris
authors.affiliation: Medical Chronobiology Program (C.J.M., T.E.P., J.M., F.A.J.L.S.), Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts 02115; and Division of Sleep Medicine (C.J.M., F.A.J.L.S.), Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Taylor E
authors.initials: TE
authors.lastname: Purvis
authors.affiliation: Medical Chronobiology Program (C.J.M., T.E.P., J.M., F.A.J.L.S.), Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts 02115; and Division of Sleep Medicine (C.J.M., F.A.J.L.S.), Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Joseph
authors.initials: J
authors.lastname: Mistretta
authors.affiliation: Medical Chronobiology Program (C.J.M., T.E.P., J.M., F.A.J.L.S.), Division of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, Massachusetts 02115; and Division of Sleep Medicine (C.J.M., F.A.J.L.S.), Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Frank A J L
authors.initials: FA
authors.lastname: Scheer
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D021081:Chronobiology Disorders / Q000150:complications* / Q000503:physiopathology; D002940:Circadian Rhythm / Q000502:physiology*; D018592:Cross-Over Studies; D004032:Diet; D005260:Female; D018149:Glucose Intolerance / Q000209:etiology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000502:physiology; D008297:Male; D062407:Meals; D008875:Middle Aged; D019518:Postprandial Period; D012890:Sleep; D014940:Work Schedule Tolerance / Q000502:physiology*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D006854:Hydrocortisone