title: A Predictive Metabolic Signature for the Transition From Gestational Diabetes Mellitus to Type 2 Diabetes.
abstract: Gestational diabetes mellitus (GDM) affects 3-14% of pregnancies, with 20-50% of these women progressing to type 2 diabetes (T2D) within 5 years. This study sought to develop a metabolomics signature to predict the transition from GDM to T2D. A prospective cohort of 1,035 women with GDM pregnancy were enrolled at 6-9 weeks postpartum (baseline) and were screened for T2D annually for 2 years. Of 1,010 women without T2D at baseline, 113 progressed to T2D within 2 years. T2D developed in another 17 women between 2 and 4 years. A nested case-control design used 122 incident case patients matched to non-case patients by age, prepregnancy BMI, and race/ethnicity. We conducted metabolomics with baseline fasting plasma and identified 21 metabolites that significantly differed by incident T2D status. Machine learning optimization resulted in a decision tree modeling that predicted T2D incidence with a discriminative power of 83.0% in the training set and 76.9% in an independent testing set, which is far superior to measuring fasting plasma glucose levels alone. The American Diabetes Association recommends T2D screening in the early postpartum period via oral glucose tolerance testing after GDM, which is a time-consuming and inconvenient procedure. Our metabolomics signature predicted T2D incidence from a single fasting blood sample. This study represents the first metabolomics study of the transition from GDM to T2D validated in an independent testing set, facilitating early interventions.
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada.
authors.forename: Amina
authors.initials: A
authors.lastname: Allalou
authors.affiliation: Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark Department of Physiology, University of Toronto, Ontario, Canada.
authors.forename: Amarnadh
authors.initials: A
authors.lastname: Nalla
authors.affiliation: Department of Physiology, University of Toronto, Ontario, Canada.
authors.forename: Kacey J
authors.initials: KJ
authors.lastname: Prentice
authors.affiliation: Department of Physiology, University of Toronto, Ontario, Canada.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Physiology, University of Toronto, Ontario, Canada.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Physiology, University of Toronto, Ontario, Canada.
authors.forename: Feihan F
authors.initials: FF
authors.lastname: Dai
authors.affiliation: Kaiser Permanente Northern California, Division of Research, Oakland, CA.
authors.forename: Xian
authors.initials: X
authors.lastname: Ning
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada Department of Molecular Genetics, University of Toronto, Ontario, Canada.
authors.forename: Lucy R
authors.initials: LR
authors.lastname: Osborne
authors.affiliation: Department of Physiology, University of Toronto, Ontario, Canada Department of Obstetrics and Gynaecology, University of Toronto, Ontario, Canada.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Cox
authors.affiliation: Kaiser Permanente Northern California, Division of Research, Oakland, CA erica.gunderson@kp.org michael.wheeler@utoronto.ca.
authors.forename: Erica P
authors.initials: EP
authors.lastname: Gunderson
authors.affiliation: Department of Medicine, University of Toronto, Ontario, Canada Department of Physiology, University of Toronto, Ontario, Canada erica.gunderson@kp.org michael.wheeler@utoronto.ca.
authors.forename: Michael B
authors.initials: MB
authors.lastname: Wheeler
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000453:epidemiology*; D016640:Diabetes, Gestational / Q000097:blood / Q000453:epidemiology*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D049590:Postpartum Period / Q000097:blood; D011247:Pregnancy; D011446:Prospective Studies; D055815:Young Adult
chemical_list: D001786:Blood Glucose