Abstract:
CONTEXT: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. DESIGN, SETTING, PATIENTS, AND INTERVENTIONS: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. MAIN OUTCOMES: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). CONCLUSION: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.
journal_name
Pediatr Diabetesjournal_title
Pediatric diabetesauthors
Sharma AN,Wigham J,Veldhuis JDdoi
10.1111/pedi.12108subject
Has Abstractpub_date
2014-09-01 00:00:00pages
444-52issue
6eissn
1399-543Xissn
1399-5448journal_volume
15pub_type
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pub_type: 杂志文章
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doi:10.1111/pedi.12995
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doi:10.1111/j.1399-5448.2008.00472.x
更新日期:2009-05-01 00:00:00
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journal_title:Pediatric diabetes
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journal_title:Pediatric diabetes
pub_type: 杂志文章
doi:10.1111/j.1399-5448.2006.00201.x
更新日期:2006-10-01 00:00:00
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journal_title:Pediatric diabetes
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更新日期:2015-05-01 00:00:00
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journal_title:Pediatric diabetes
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journal_title:Pediatric diabetes
pub_type: 杂志文章
doi:10.1111/pedi.13077
更新日期:2020-07-13 00:00:00
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journal_title:Pediatric diabetes
pub_type: 杂志文章
doi:10.1111/j.1399-543X.2004.00059.x
更新日期:2004-12-01 00:00:00
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journal_title:Pediatric diabetes
pub_type: 杂志文章
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journal_title:Pediatric diabetes
pub_type: 杂志文章
doi:10.1111/pedi.12409
更新日期:2017-09-01 00:00:00
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journal_title:Pediatric diabetes
pub_type: 杂志文章
doi:10.1111/j.1399-5448.2009.00590.x
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journal_title:Pediatric diabetes
pub_type: 杂志文章
doi:10.1111/j.1399-5448.2007.00280.x
更新日期:2007-10-01 00:00:00
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journal_title:Pediatric diabetes
pub_type: 杂志文章,多中心研究
doi:10.1111/pedi.12066
更新日期:2014-03-01 00:00:00
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journal_title:Pediatric diabetes
pub_type: 杂志文章
doi:10.1111/pedi.12771
更新日期:2019-03-01 00:00:00
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更新日期:2009-09-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1399-5448.2010.00686.x
更新日期:2011-05-01 00:00:00
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journal_title:Pediatric diabetes
pub_type: 杂志文章,随机对照试验
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更新日期:2008-04-01 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2017-06-01 00:00:00
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journal_title:Pediatric diabetes
pub_type: 杂志文章
doi:10.1111/j.1399-5448.2012.00865.x
更新日期:2012-11-01 00:00:00
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pub_type: 杂志文章
doi:10.1111/j.1399-5448.2009.00549.x
更新日期:2010-05-01 00:00:00
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journal_title:Pediatric diabetes
pub_type: 杂志文章
doi:10.1111/j.1399-5448.2012.00894.x
更新日期:2013-02-01 00:00:00
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journal_title:Pediatric diabetes
pub_type: 杂志文章
doi:10.1111/j.1399-5448.2008.00487.x
更新日期:2009-05-01 00:00:00
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journal_title:Pediatric diabetes
pub_type: 杂志文章
doi:10.1111/pedi.12596
更新日期:2018-05-01 00:00:00