title: Concentrations of the stress hormone copeptin increase upon hypoglycaemia in patients with type 1 diabetes dependent of hypoglycaemia awareness.
abstract: OBJECTIVE
  Copeptin, a marker for stress mirroring vasopressin concentrations, has been shown to increase upon insulin-induced hypoglycaemia in patients after transsphenoidal surgery of pituitary adenomas. Patients with type 1 diabetes mellitus are prone to hypoglycaemia, but no data about copeptin levels upon hypoglycaemia are available. Furthermore, the perception of hypoglycaemia can vary from total unawareness to disabling episodes. The aim of this study was to investigate whether copeptin increases upon hypoglycaemia in patients with type 1 diabetes mellitus and is associated with the degree of hypoglycaemia awareness.
  
  
  METHODS
  In this prospective observational study, 17 patients with type 1 diabetes underwent a standardized insulin infusion test. Blood sampling for glucose and copeptin was performed at baseline and after 60 minutes (min). To assess hypoglycaemia associated symptoms the Mood and Symptom Questionnaire (MSQ) was conducted at baseline and after 60 min.
  
  
  RESULTS
  During insulin infusion, blood glucose decreased from 5.1 (SD±0.2) to 3.0 (±0.5) mmol/L at 60 min (p<0.001). Copeptin concentrations increased from 3.2 (±1.7) to 3.8 (±1.9) pmol/L (p = 0.03). Mood and Symptoms Questionnaire scores increased from 14 (±3.0) to 18 (±5.8), (p = 0.006). Patients with good hypoglycaemia awareness had an increase in copeptin from 3.0 (±1.8) to 4.2 (±2.4) pmol/L (p = 0.03) in contrast to patients more unaware of hypoglycaemia who only showed an increase in copeptin from 3.3 (±1.6) to 3.6 (±1.4) pmol/L (p = 0.4). There was a trend to a larger copeptin increase in patients aware of hypoglycemia compared to patients unaware of hypoglycemia (p = 0.074).
  
  
  CONCLUSIONS
  Copeptin increases in patients with type 1 diabetes upon insulin induced hypoglycaemia. Interestingly, the copeptin increase seems associated with the degree of hypoglycaemia awareness. This hypothesis warrants further verification.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00515801.
authors.affiliation: Department of Diabetology, Endocrinology and Metabolism, University Hospital Basel, Basel, Switzerland.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Seelig
authors.forename: Stefan
authors.initials: S
authors.lastname: Bilz
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keller
authors.forename: Fabian
authors.initials: F
authors.lastname: Meienberg
authors.forename: Mirjam
authors.initials: M
authors.lastname: Christ-Crain
mesh_terms: D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000150:complications*; D005260:Female; D006020:Glycopeptides / Q000097:blood*; D007722:Health Knowledge, Attitudes, Practice; D006801:Humans; D007003:Hypoglycemia / Q000097:blood* / Q000150:complications*; D008297:Male
chemical_list: D006020:Glycopeptides; C048197:copeptins
references.citation: Front Neuroendocrinol. 1993 Apr;14(2):76-122
references.pmid: 8387436
references.citation: Diabet Med. 1989 Mar;6(2):158-63
references.pmid: 2522860
references.citation: Peptides. 2005 Dec;26(12):2500-4
references.pmid: 15922490
references.citation: Lancet. 1977 Aug 27;2(8035):428-30
references.pmid: 70644
references.citation: J Am Coll Cardiol. 2009 Jun 30;54(1):60-8
references.pmid: 19555842
references.citation: Diabetes. 2008 Dec;57(12):3169-76
references.pmid: 19033403
references.citation: N Engl J Med. 2004 May 27;350(22):2272-9
references.pmid: 15163777
references.citation: Life Sci. 1998;62(22):1985-98
references.pmid: 9627097
references.citation: J Clin Endocrinol Metab. 2007 Jul;92(7):2640-3
references.pmid: 17426098
references.citation: Ann N Y Acad Sci. 2010 Nov;1212:12-28
references.pmid: 21039590
references.citation: Am J Med. 1995 Jan;98(1):22-31
references.pmid: 7825615
references.citation: Clin Chem. 2006 Jan;52(1):112-9
references.pmid: 16269513
references.citation: Hypertension. 1983 Mar-Apr;5(2 Pt 2):I129-38
references.pmid: 6826223
references.citation: Ann Neurol. 2009 Dec;66(6):799-808
references.pmid: 20035506
references.citation: Eur J Clin Invest. 2007 Feb;37(2):145-52
references.pmid: 17217381
references.citation: J Clin Endocrinol Metab. 1989 Mar;68(3):688-92
references.pmid: 2645315
references.citation: Shock. 2007 Aug;28(2):219-26
references.pmid: 17515850
references.citation: J Clin Invest. 1973 Sep;52(9):2340-52
references.pmid: 4727463