title: Diabetes is associated with impairment of uterine contractility and high Caesarean section rate.
abstract: OBJECTIVE
  The prevalence of births worldwide complicated by diabetes mellitus is increasing. In the UK, for example, <25% of diabetic women have a non-instrumental vaginal delivery. Strikingly, more than half the Caesarean sections (CS) in these patients are non-elective, but the reasons for this are not understood. We have tested the hypothesis that poor myometrial contractility as a consequence of the disease contributes to this high CS rate.
  
  
  METHODS
  We compared spontaneous, high K depolarisation and oxytocin-induced contractions from diabetic and matched control patients having an elective CS. To investigate the mechanism of any differences we measured intracellular Ca, and performed western blotting and compared the tissues histologically.
  
  
  RESULTS
  There was significantly decreased contraction amplitude and duration in uteri from diabetic compared with control patients, even when possible confounders such as BMI were analysed. Reduced intracellular calcium signals and expression of calcium entry channels were found in uteruses from diabetic patients, which, along with a reduction in muscle content found on histological examination, could explain the reduced force. Myometrium from diabetic patients was responsive to oxytocin, but still did not reach the levels found in non-diabetic patients.
  
  
  CONCLUSIONS
  These are the first data investigating myometrium in diabetic patients and they support the hypothesis that there is poorer contractility even in the presence of oxytocin. The underlying mechanism is related to reduced Ca channel expression and intracellular calcium signals and a decrease in muscle mass. We conclude that these factors significantly contribute to the increased emergency CS rate in diabetic patients.
authors.affiliation: Department of Molecular and Cellular Physiology, Institute of Translational Medicine, University of Liverpool, Crown Street, Liverpool L69 3BX, UK.
authors.forename: S
authors.initials: S
authors.lastname: Al-Qahtani
authors.forename: A
authors.initials: A
authors.lastname: Heath
authors.forename: S
authors.initials: S
authors.lastname: Quenby
authors.forename: F
authors.initials: F
authors.lastname: Dawood
authors.forename: R
authors.initials: R
authors.lastname: Floyd
authors.forename: T
authors.initials: T
authors.lastname: Burdyga
authors.forename: S
authors.initials: S
authors.lastname: Wray
mesh_terms: D000328:Adult; D015992:Body Mass Index; D002118:Calcium / Q000737:chemistry; D015220:Calcium Channels / Q000737:chemistry; D002585:Cesarean Section / Q000706:statistics & numerical data*; D048909:Diabetes Complications / Q000503:physiopathology; D003920:Diabetes Mellitus / Q000503:physiopathology*; D016640:Diabetes, Gestational / Q000378:metabolism; D005260:Female; D006801:Humans; D010121:Oxytocin / Q000737:chemistry; D011247:Pregnancy; D011248:Pregnancy Complications; D015398:Signal Transduction; D014590:Uterine Contraction / Q000378:metabolism*
chemical_list: D015220:Calcium Channels; D010121:Oxytocin; D002118:Calcium
references.citation: N Engl J Med. 2005 Jun 16;352(24):2477-86
references.pmid: 15951574
references.citation: BMJ. 2004 Apr 17;328(7445):915
references.pmid: 15066886
references.citation: J Physiol. 1999 Oct 1;520 Pt 1:153-63
references.pmid: 10517808
references.citation: Eur J Pharmacol. 1998 Jun 5;350(2-3):237-41
references.pmid: 9696413
references.citation: J Soc Gynecol Investig. 2003 Jul;10(5):252-64
references.pmid: 12853086
references.citation: Diabet Med. 2003 Sep;20(9):734-8
references.pmid: 12925053
references.citation: Diabetes Care. 1999 Sep;22(9):1561-7
references.pmid: 10480526
references.citation: J Physiol. 1997 Mar 1;499 ( Pt 2):485-96
references.pmid: 9080376
references.citation: J Pharmacol Exp Ther. 1984 Dec;231(3):603-9
references.pmid: 6094794
references.citation: J Mol Histol. 2005 Feb;36(1-2):1-14
references.pmid: 15703994
references.citation: Diabetes Metab. 2003 Apr;29(2 Pt 1):175-8
references.pmid: 12746640
references.citation: Prostaglandins. 1996 May;51(5):307-20
references.pmid: 8792441
references.citation: Proc Soc Exp Biol Med. 1985 Dec;180(3):497-504
references.pmid: 4080698
references.citation: Br J Pharmacol. 1991 Dec;104(4):928-32
references.pmid: 1810603
references.citation: J Urol. 2000 Apr;163(4):1357-63
references.pmid: 10737543
references.citation: J Pharmacol Exp Ther. 1990 Jun;253(3):1057-62
references.pmid: 1694242
references.citation: BJOG. 2000 Oct;107(10):1309-11
references.pmid: 11028587
references.citation: Diabetes. 1999 Jun;48(6):1323-30
references.pmid: 10342823
references.citation: Am J Physiol Heart Circ Physiol. 2000 Mar;278(3):H714-22
references.pmid: 10710338
references.citation: Pharmacology. 1992;45(2):90-8
references.pmid: 1523218
references.citation: Reproduccion. 1975 Jan-Mar;2(1):31-8
references.pmid: 1181206
references.citation: BJOG. 2002 Mar;109(3):289-96
references.pmid: 11950184
references.citation: Diabetes. 2007 Nov;56(11):2780-9
references.pmid: 17666471
references.citation: J Cardiothorac Vasc Anesth. 2002 Aug;16(4):502-7
references.pmid: 12154435
references.citation: Ann N Y Acad Sci. 2006 Nov;1084:208-22
references.pmid: 17151303
references.citation: Pflugers Arch. 1998 Oct;436(5):801-3
references.pmid: 9716716
references.citation: Am J Physiol. 1982 Apr;242(4):H490-5
references.pmid: 7039365
references.citation: Cell Calcium. 2010 Jan;47(1):47-54
references.pmid: 19969350
references.citation: J Matern Fetal Neonatal Med. 2004 Jan;15(1):61-7
references.pmid: 15101614
references.citation: J Vasc Res. 1996 Nov-Dec;33(6):454-62
references.pmid: 8998194
references.citation: Prostaglandins. 1988 Feb;35(2):191-205
references.pmid: 3129757
references.citation: Urology. 2001 Jun;57(6 Suppl 1):110-1
references.pmid: 11378077
references.citation: Am J Obstet Gynecol. 2004 Sep;191(3):969-74
references.pmid: 15467574
references.citation: Ann N Y Acad Sci. 2007 Apr;1101:85-96
references.pmid: 17303831
references.citation: Br J Pharmacol. 1990 Oct;101(2):465-71
references.pmid: 2257445
references.citation: JAMA. 1996 Apr 17;275(15):1165-70
references.pmid: 8609683
references.citation: Eur J Pharmacol. 2005 Feb 10;509(1):77-83
references.pmid: 15713432
references.citation: Am J Obstet Gynecol. 2004 Sep;191(3):958-63
references.pmid: 15467572
references.citation: Am J Obstet Gynecol. 2005 Jun;192(6):1768-76
references.pmid: 15970805
references.citation: Hum Reprod. 2009 Jan;24(1):45-54
references.pmid: 18835875
references.citation: J Physiol. 1993 Jun;465:629-45
references.pmid: 8229854
references.citation: Diabetes Care. 2004 Dec;27(12):2819-23
references.pmid: 15562191
references.citation: Pflugers Arch. 2001 Oct;443(1):112-4
references.pmid: 11692274
references.citation: Eur J Pharmacol. 1991 Oct 2;203(1):79-84
references.pmid: 1724653
references.citation: Am J Physiol Heart Circ Physiol. 2005 Mar;288(3):H1233-41
references.pmid: 15528227
references.citation: J Reprod Med. 1999 Feb;44(2):115-21
references.pmid: 10853442
references.citation: BJOG. 2008 Mar;115(4):445-52
references.pmid: 18271881
references.citation: J Clin Invest. 1996 Dec 1;98(11):2564-71
references.pmid: 8958219
references.citation: J Urol. 2000 Jan;163(1):323-30
references.pmid: 10604384