title: Later chronotype is associated with higher hemoglobin A1c in prediabetes patients.
abstract: The circadian system is known to play a role in glucose metabolism. Chronotype reflects the interindividual variability in the phase of entrainment. Those with later chronotype typically prefer later times in the day for different activities such as sleep or meals. Later chronotype has been shown to be associated with metabolic syndrome, increased diabetes risk and poorer glycemic control in type 2 diabetes patients. In addition, "social jetlag", a form of circadian misalignment due to a mismatch between social rhythms and the circadian clock, has been shown to be associated with insulin resistance. Other sleep disturbances (insufficient sleep, poor sleep quality and sleep apnea) have also been shown to affect glucose metabolism. In this study, we explored whether there was a relationship between chronotype, social jetlag and hemoglobin A1c (HbA1c) levels in prediabetes patients, independent of other sleep disturbances. A cross-sectional study was conducted at the Department of Family Medicine, Ramathibodi Hospital, Bangkok, from October 2014 to March 2016 in 1014 non-shift working adults with prediabetes. Mid-sleep time on free day adjusted for sleep debt (MSFsc) was used as an indicator of chronotype. Social jetlag was calculated based on the absolute difference between mid-sleep time on weekdays and weekends. The most recent HbA1c values and lipid levels were retrieved from clinical laboratory databases. Univariate analyses revealed that later MSFsc (p = 0.028) but not social jetlag (p = 0.48) was significantly associated with higher HbA1c levels. Multivariate linear regression analysis was applied to determine whether an independent association between MSFsc and HbA1c level existed. After adjusting for age, sex, alcohol use, body mass index (BMI), social jetlag, sleep duration, sleep quality and sleep apnea risk, later MSFsc was significantly associated with higher HbA1c level (B = 0.019, 95% CI: 0.00001, 0.038, p = 0.049). The effect size of one hour later MSFsc on HbA1c (standardized coefficient = 0.065) was approximately 74% of that of the effect of one unit (kg/m2) increase in BMI (standardized coefficient = 0.087). In summary, later chronotype is associated with higher HbA1c levels in patients with prediabetes, independent of social jetlag and other sleep disturbances. Further research regarding the potential role of chronotype in diabetes prevention should be explored.
authors.affiliation: a Department of Family Medicine , Faculty of Medicine Ramathibodi Hospital, Mahidol University , Bangkok , Thailand.|b Section for Clinical Epidemiology and Biostatistics , Faculty of Medicine Ramathibodi Hospital, Mahidol University , Bangkok , Thailand.
authors.forename: Thunyarat
authors.initials: T
authors.lastname: Anothaisintawee
authors.affiliation: a Department of Family Medicine , Faculty of Medicine Ramathibodi Hospital, Mahidol University , Bangkok , Thailand.
authors.forename: Dumrongrat
authors.initials: D
authors.lastname: Lertrattananon
authors.affiliation: a Department of Family Medicine , Faculty of Medicine Ramathibodi Hospital, Mahidol University , Bangkok , Thailand.
authors.forename: Sangsulee
authors.initials: S
authors.lastname: Thamakaison
authors.affiliation: c Section of Pulmonary and Critical Care, Department of Medicine , The University of Chicago , Chicago , Illinois , USA.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Knutson
authors.affiliation: b Section for Clinical Epidemiology and Biostatistics , Faculty of Medicine Ramathibodi Hospital, Mahidol University , Bangkok , Thailand.
authors.forename: Ammarin
authors.initials: A
authors.lastname: Thakkinstian
authors.affiliation: d Division of Endocrinology and Metabolism, Department of Medicine , Faculty of Medicine Ramathibodi Hospital, Mahidol University , Bangkok , Thailand.
authors.forename: Sirimon
authors.initials: S
authors.lastname: Reutrakul
mesh_terms: D000328:Adult; D057906:Circadian Clocks / Q000502:physiology; D002940:Circadian Rhythm / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006801:Humans; D020179:Jet Lag Syndrome / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000378:metabolism*; D012890:Sleep / Q000502:physiology*; D013997:Time Factors
chemical_list: D006442:Glycated Hemoglobin
keywords: Chronotype; circadian rhythm; hemoglobin A1c; prediabetes; sleep