title: Corticotropic axis drive of overnight cortisol secretion is suppressed in adolescents and young adults with type 1 diabetes mellitus.
abstract: BACKGROUND
  Type 1 diabetes mellitus (T1DM) is a pro-inflammatory stress state, which, with its attendant hyperglycemia, likely disrupts hypothalamo-pituitary-adrenal (HPA) control, further dysregulating glucose homeostasis.
  
  
  OBJECTIVE
  To test the hypothesis that endogenous adrenocorticotropic hormone (ACTH)-cortisol dose-responsive drive, estimated analytically, is significantly accentuated in adolescents and young adults with T1DM compared with healthy individuals.
  
  
  METHODS
  This was a pilot study of 11 volunteers with T1DM and 10 controls, ages 16-30 yr, at a medical center. Subjects underwent overnight frequent blood sampling (every 10 min for ACTH and cortisol and every 60 min for blood glucose) from 10 pm to 8 am. T1DM volunteers maintained their home insulin regimen.
  
  
  RESULTS
  Deconvolution analysis and dose-response estimates were the key outcomes.
  
  
  RESULTS
  Mean free cortisol, but not ACTH, concentrations were lower in the T1DM group compared with controls (p = 0.012). Non-invasive ACTH-cortisol dose-response estimates revealed that T1DM patients had reduced ACTH efficacy (maximal cortisol secretion, p = 0.009), reduced ACTH potency as quantified by greater EC50 (ACTH concentration driving half-maximal cortisol secretion, p = 0.04), and increased ACTH sensitivity (more positive ACTH-cortisol slope, p = 0.03). Post-hoc gender comparisons indicated that these differences were limited to females. Linear regression in women showed a strong correlation of both ACTH efficacy and EC50 with C-peptide levels (both p < 0.01).
  
  
  CONCLUSIONS
  Compared with healthy individuals, T1DM patients manifest decreased overnight adrenal responsiveness to endogenous ACTH leading to lower free cortisol concentrations. These findings suggest impaired stress-related adaptations of the HPA axis in T1DM.
authors.affiliation: Children's Hospital Central California, Madera, CA, 93636-8762, USA; Endocrine Research Unit, Center for Translational Science Activities, Mayo Clinic, Rochester, MN, 55905, USA.
authors.forename: Animesh N
authors.initials: AN
authors.lastname: Sharma
authors.forename: Jean
authors.initials: J
authors.lastname: Wigham
authors.forename: Johannes D
authors.initials: JD
authors.lastname: Veldhuis
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood*; D000328:Adult; D016022:Case-Control Studies; D002940:Circadian Rhythm / Q000502:physiology*; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism* / Q000503:physiopathology*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D010865:Pilot Projects; D055815:Young Adult
chemical_list: D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone
keywords: ACTH; HPA axis; adolescents; cortisol; diabetes