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The association of falling insulin requirements with maternal biomarkers and placental dysfunction: A prospective study of women with preexisting diabetes in pregnancy

Padmanabhan, Suja; Lee, Vincent W. S; Mclean, Marc; Athayde, Neil; Lanzarone, V; Khoshnow, Qemer; Peek, Michael; Cheung, N Wah

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OBJECTIVE To investigate the association of falling insulin requirements (FIR) among women with preexisting diabetes with adverse obstetric outcomes and maternal biomarkers longitudinally in pregnancy. RESEARCH DESIGN AND METHODS A multicenter prospective cohort study of 158 women (41 with type 1 diabetes and 117 with type 2 diabetes) was conducted. Women with FIR of ≥15% from the peak total daily dose after 20 weeks' gestation were considered case subjects (n = 32). The primary outcome was a...[Show more]

dc.contributor.authorPadmanabhan, Suja
dc.contributor.authorLee, Vincent W. S
dc.contributor.authorMclean, Marc
dc.contributor.authorAthayde, Neil
dc.contributor.authorLanzarone, V
dc.contributor.authorKhoshnow, Qemer
dc.contributor.authorPeek, Michael
dc.contributor.authorCheung, N Wah
dc.date.accessioned2021-09-23T04:57:55Z
dc.identifier.issn0149-5992
dc.identifier.urihttp://hdl.handle.net/1885/248715
dc.description.abstractOBJECTIVE To investigate the association of falling insulin requirements (FIR) among women with preexisting diabetes with adverse obstetric outcomes and maternal biomarkers longitudinally in pregnancy. RESEARCH DESIGN AND METHODS A multicenter prospective cohort study of 158 women (41 with type 1 diabetes and 117 with type 2 diabetes) was conducted. Women with FIR of ≥15% from the peak total daily dose after 20 weeks' gestation were considered case subjects (n = 32). The primary outcome was a composite of clinical markers of placental dysfunction (preeclampsia, small for gestational age [≤5th centile], stillbirth, premature delivery [<30 weeks], and placental abruption). Maternal circulating angiogenic markers (placental growth factor [PlGF] and soluble fms-like tyrosine kinase 1 [sFlt-1]), placental hormones (human placental lactogen, progesterone, and tumor necrosis factor-α), HbA1c, and creatinine were studied serially during pregnancy. RESULTS FIR ≥15% were associated with an increased risk of the composite primary outcome (odds ratio [OR] 4.38 [95% CI 1.9–10.3]; P < 0.001), preeclampsia (OR 6.76 [95% CI 2.7–16.7]; P < 0.001), and was more common among women with type 1 diabetes (36.6 vs. 14.5%; P = 0.002). Creatinine was modestly elevated among women with FIR ≥15%; however, there was no difference in HbA1c. The ratio of sFlt-1 to PlGF was significantly higher among women with FIR at 25, 30, and 36 weeks, with differences maintained in the subgroup that developed preeclampsia. There was no difference in placental hormones between the groups. CONCLUSIONS This is the first prospective study to associate FIR with altered expression of placental antiangiogenic factors and preeclampsia. FIR are an important clinical sign, among women with preexisting diabetes, that should alert the clinician to investigate underlying placental dysfunction.
dc.description.sponsorshipThe authors thank Westmead Medical Research Foundation for funding the study.
dc.format.mimetypeapplication/pdf
dc.language.isoen_AU
dc.publisherAmerican Diabetes Association
dc.rights© 2017 by the American Diabetes Association
dc.sourceDiabetes Care
dc.titleThe association of falling insulin requirements with maternal biomarkers and placental dysfunction: A prospective study of women with preexisting diabetes in pregnancy
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume40
dc.date.issued2017
local.identifier.absfor111402 - Obstetrics and Gynaecology
local.identifier.ariespublicationa383154xPUB8877
local.publisher.urlhttp://www.diabetes.org/
local.type.statusPublished Version
local.contributor.affiliationPadmanabhan, Suja, Westmead Hospital, Sydney
local.contributor.affiliationLee, Vincent W. S, University of Sydney
local.contributor.affiliationMclean, Marc, Westmead Hospital, Sydney
local.contributor.affiliationAthayde, Neil, Westmead Hospital, Sydney
local.contributor.affiliationLanzarone, V, Nepean Hospital
local.contributor.affiliationKhoshnow, Qemer, Nepean Hospital, Sydney
local.contributor.affiliationPeek, Michael, College of Health and Medicine, ANU
local.contributor.affiliationCheung, N Wah, University of Sydney
local.description.embargo2099-12-31
local.bibliographicCitation.issue10
local.bibliographicCitation.startpage1323
local.bibliographicCitation.lastpage1330
local.identifier.doi10.2337/dc17-0391
local.identifier.absseo920114 - Reproductive System and Disorders
local.identifier.absseo920104 - Diabetes
dc.date.updated2020-11-23T11:14:33Z
local.identifier.scopusID2-s2.0-85032615029
CollectionsANU Research Publications

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