title: Lack of significant association between type 2 diabetes mellitus with longitudinal change in diurnal salivary cortisol: the multiethnic study of atherosclerosis.
abstract: Cross-sectional association has been shown between type 2 diabetes and hypothalamic-pituitary-adrenal (HPA) axis dysregulation; however, the temporality of this association is unknown. Our aim was to determine if type 2 diabetes is associated with longitudinal change in daily cortisol curve features. We hypothesized that the presence of type 2 diabetes may lead to a more blunted and abnormal HPA axis profile over time, suggestive of increased HPA axis dysregulation. This was a longitudinal cohort study, including 580 community-dwelling individuals (mean age 63.7 ± 9.1 years; 52.8 % women) with (n = 90) and without (n = 490) type 2 diabetes who attended two MultiEthnic Study of Atherosclerosis Stress ancillary study exams separated by 6 years. Outcome measures that were collected were wake-up and bedtime cortisol, cortisol awakening response (CAR), total area under the curve (AUC), and early, late, and overall decline slopes. In univariate analyses, wake-up and AUC increased over 6 years more in persons with as compared to those without type 2 diabetes (11 vs. 7 % increase for wake-up and 17 vs. 11 % for AUC). The early decline slope became flatter over time with a greater flattening observed in diabetic compared to non-diabetic individuals (23 vs. 9 % flatter); however, the change was only statistically significant for wake-up cortisol (p-value: 0.03). Over time, while CAR was reduced more, late decline and overall decline became flatter, and bedtime cortisol increased less in those with as compared to those without type 2 diabetes, none of these changes were statistically significant in adjusted models. We did not identify any statistically significant change in cortisol curve features over 6 years by type 2 diabetes status.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, 1830 E. Monument Street, Suite 333, Baltimore, MD, 21287, USA.
authors.forename: Elias K
authors.initials: EK
authors.lastname: Spanakis
authors.affiliation: Department of Epidemiology, Drexel University School of Public Health, Philadelphia, PA, USA.
authors.forename: Xu
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Brisa N
authors.initials: BN
authors.lastname: Sánchez
authors.affiliation: Department of Epidemiology, Drexel University School of Public Health, Philadelphia, PA, USA.
authors.forename: Ana V
authors.initials: AV
authors.lastname: Diez Roux
authors.affiliation: Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Belinda L
authors.initials: BL
authors.lastname: Needham
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, 1830 E. Monument Street, Suite 333, Baltimore, MD, 21287, USA.
authors.forename: Gary S
authors.initials: GS
authors.lastname: Wand
authors.affiliation: Division of Geriatrics, David Geffen School of Medicine, University of California, Los Angeles, CA, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Seeman
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Johns Hopkins University School of Medicine, 1830 E. Monument Street, Suite 333, Baltimore, MD, 21287, USA. sahill@jhmi.edu.|Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. sahill@jhmi.edu.
authors.forename: Sherita Hill
authors.initials: SH
authors.lastname: Golden
mesh_terms: D000368:Aged; D002940:Circadian Rhythm / Q000502:physiology*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D012463:Saliva / Q000737:chemistry*
chemical_list: D006854:Hydrocortisone
keywords: Cortisol; Diabetes; Epidemiology; HPA axis; Stress