title: Early Antenatal Prediction of Gestational Diabetes in Obese Women: Development of Prediction Tools for Targeted Intervention.
abstract: All obese women are categorised as being of equally high risk of gestational diabetes (GDM) whereas the majority do not develop the disorder. Lifestyle and pharmacological interventions in unselected obese pregnant women have been unsuccessful in preventing GDM. Our aim was to develop a prediction tool for early identification of obese women at high risk of GDM to facilitate targeted interventions in those most likely to benefit. Clinical and anthropometric data and non-fasting blood samples were obtained at 15+0-18+6 weeks' gestation in 1303 obese pregnant women from UPBEAT, a randomised controlled trial of a behavioural intervention. Twenty one candidate biomarkers associated with insulin resistance, and a targeted nuclear magnetic resonance (NMR) metabolome were measured. Prediction models were constructed using stepwise logistic regression. Twenty six percent of women (n = 337) developed GDM (International Association of Diabetes and Pregnancy Study Groups criteria). A model based on clinical and anthropometric variables (age, previous GDM, family history of type 2 diabetes, systolic blood pressure, sum of skinfold thicknesses, waist:height and neck:thigh ratios) provided an area under the curve of 0.71 (95%CI 0.68-0.74). This increased to 0.77 (95%CI 0.73-0.80) with addition of candidate biomarkers (random glucose, haemoglobin A1c (HbA1c), fructosamine, adiponectin, sex hormone binding globulin, triglycerides), but was not improved by addition of NMR metabolites (0.77; 95%CI 0.74-0.81). Clinically translatable models for GDM prediction including readily measurable variables e.g. mid-arm circumference, age, systolic blood pressure, HbA1c and adiponectin are described. Using a ≥35% risk threshold, all models identified a group of high risk obese women of whom approximately 50% (positive predictive value) later developed GDM, with a negative predictive value of 80%. Tools for early pregnancy identification of obese women at risk of GDM are described which could enable targeted interventions for GDM prevention in women who will benefit the most.
authors.affiliation: Division of Women's Health, King's College London, London, United Kingdom.
authors.forename: Sara L
authors.initials: SL
authors.lastname: White
authors.affiliation: MRC Integrative Epidemiology Unit at the University of Bristol, Bristol, United Kingdom.|School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
authors.forename: Debbie A
authors.initials: DA
authors.lastname: Lawlor
authors.affiliation: Division of Women's Health, King's College London, London, United Kingdom.|Guy's & St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Annette L
authors.initials: AL
authors.lastname: Briley
authors.affiliation: MRC Lifecourse Epidemiology Unit and NIHR Southampton Biomedical Research Centre, University of Southampton, Southampton, United Kingdom.|University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom.
authors.forename: Keith M
authors.identifier: http://orcid.org/0000-0002-4643-0618
authors.initials: KM
authors.lastname: Godfrey
authors.affiliation: School of Medicine, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Nelson
authors.affiliation: Division of Women's Health, King's College London, London, United Kingdom.|Guy's & St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Eugene
authors.initials: E
authors.lastname: Oteng-Ntim
authors.affiliation: Institute of Cellular Medicine, Uterine Cell Signalling Group, Newcastle University, Newcastle Upon Tyne, United Kingdom.
authors.forename: Stephen C
authors.identifier: http://orcid.org/0000-0001-7897-7987
authors.initials: SC
authors.lastname: Robson
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Naveed
authors.initials: N
authors.lastname: Sattar
authors.affiliation: Division of Women's Health, King's College London, London, United Kingdom.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Seed
authors.affiliation: Division of Women's Health, King's College London, London, United Kingdom.
authors.forename: Matias C
authors.identifier: http://orcid.org/0000-0002-8076-4275
authors.initials: MC
authors.lastname: Vieira
authors.affiliation: Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Welsh
authors.affiliation: Maternity Services, Central Manchester University Hospitals NHS Foundation Trust, Manchester, United Kingdom.|Maternal and Fetal Health Research Centre, University of Manchester, Manchester, United Kingdom.
authors.forename: Melissa
authors.initials: M
authors.lastname: Whitworth
authors.affiliation: Division of Women's Health, King's College London, London, United Kingdom.
authors.forename: Lucilla
authors.initials: L
authors.lastname: Poston
authors.affiliation: Division of Women's Health, King's College London, London, United Kingdom.|Guy's & St Thomas' NHS Foundation Trust, London, United Kingdom.
authors.forename: Dharmintra
authors.initials: D
authors.lastname: Pasupathy
mesh_terms: D000328:Adult; D016640:Diabetes, Gestational / Q000175:diagnosis*; D005260:Female; D006801:Humans; D009765:Obesity / Q000150:complications / Q000175:diagnosis*; D011247:Pregnancy; D011446:Prospective Studies