Corticotropic axis drive of overnight cortisol secretion is suppressed in adolescents and young adults with type 1 diabetes mellitus. Issue 6 (18th December 2013)

• Record Type: Journal Article
• Authors: Sharma, Animesh N; Wigham, Jean; Veldhuis, Johannes D
• Is Part Of: Pediatric diabetes. Volume 15:Issue 6(2014:Oct.)
• Page Start: 444
• Page End: 452
• Publication Date: 2013-12-18
• Subjects: Diabetes in children -- Periodicals; 616.462
• DOI: 10.1111/pedi.12108
• Languages: English
• ISSNs: 1399-543X

Abstract

<abstract abstract-type="main" id="pedi12108-abs-0001"> <title>Abstract</title> <sec id="pedi12108-sec-0001" sec-type="section"> <title>Context</title> <p id="pedi12108-para-0001">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.</p> </sec> <sec id="pedi12108-sec-0002" sec-type="section"> <title>Objective</title> <p id="pedi12108-para-0002">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.</p> </sec> <sec id="pedi12108-sec-0002a" sec-type="section"> <title>Design, setting, patients, and interventions</title> <p id="pedi12108-para-0004">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.</p> </sec> <sec id="pedi12108-sec-0003" sec-type="section"> <title>Main outcomes</title> <p id="pedi12108-para-0005">Deconvolution analysis and dose–response estimates were the key outcomes.</p> </sec> <sec id="pedi12108-sec-0004" sec-type="section"> <title>Results</title> <p id="pedi12108-para-0006">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 EC<sub>50</sub> (ACTH concentration driving half‐maximal cortisol secretion, p = 0.04), and increased ACTH sensitivity (more positive ACTH‐cortisol slope, p = 0.03). <italic>Post‐hoc</italic> gender comparisons indicated that these differences were limited to females. Linear regression in women showed a strong correlation of both ACTH efficacy and EC<sub>50</sub> with C‐peptide levels (both p < 0.01).</p> </sec> <sec id="pedi12108-sec-0005" sec-type="section"> <title>Conclusion</title> <p id="pedi12108-para-0007">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.</p> </sec> </abstract>