title: Each degree of glucose intolerance in pregnancy predicts distinct trajectories of β-cell function, insulin sensitivity, and glycemia in the first 3 years postpartum.
abstract: OBJECTIVE
  Glucose intolerance in pregnancy predicts an increased risk of future type 2 diabetes mellitus (T2DM) that is proportional to the severity of antepartum dysglycemia (i.e., highest in women with gestational diabetes mellitus [GDM], followed by those with milder dysglycemia). However, the pathophysiologic changes driving this risk are not known. Thus, we evaluated the longitudinal changes in β-cell function, insulin sensitivity, and glycemia in the first 3 years postpartum after gestational dysglycemia.
  
  
  METHODS
  A total of 337 women underwent glucose challenge test (GCT) and oral glucose tolerance test (OGTT) in pregnancy, followed by repeat OGTT at 3 months, 1 year, and 3 years postpartum. The antepartum GCT/OGTT identified four gestational glucose tolerance groups: GDM (n = 105); gestational impaired glucose tolerance (GIGT; n = 60); abnormal GCT, followed by normal glucose tolerance (NGT) on the OGTT (abnormal GCT NGT; n = 96); and normal GCT with NGT (n = 76).
  
  
  RESULTS
  At each of 3 months, 1 year, and 3 years postpartum, the prevalence of glucose intolerance increased from normal GCT NGT to abnormal GCT NGT to GIGT to GDM (all P < 0.001), whereas β-cell function, assessed by the Insulin Secretion-Sensitivity Index-2 (ISSI-2), and insulin sensitivity (Matsuda index), progressively decreased across the groups (all P < 0.002). Each group predicted distinct trajectories of ISSI-2, Matsuda index, and fasting and 2-h glucose (all P < 0.001). Notably, GDM, GIGT, and abnormal GCT NGT predicted varying rates of declining β-cell function and insulin sensitivity, as well as rising glycemia, compared with normal GCT NGT.
  
  
  CONCLUSIONS
  Each degree of gestational glucose intolerance predicts distinct trajectories of β-cell function, insulin sensitivity, and glycemia in the first 3 years postpartum that drive their differential risk of future T2DM.
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Caroline K
authors.initials: CK
authors.lastname: Kramer
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Balakumar
authors.initials: B
authors.lastname: Swaminathan
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hanley
authors.affiliation: Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Toronto, Ontario, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Connelly
authors.affiliation: Division of Obstetrics and Gynecology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Mathew
authors.initials: M
authors.lastname: Sermer
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
authors.affiliation: Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada rretnakaran@mtsinai.on.ca.
authors.forename: Ravi
authors.initials: R
authors.lastname: Retnakaran
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis* / Q000453:epidemiology / Q000503:physiopathology; D016640:Diabetes, Gestational / Q000175:diagnosis / Q000453:epidemiology / Q000378:metabolism* / Q000503:physiopathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D018149:Glucose Intolerance / Q000145:classification / Q000175:diagnosis / Q000453:epidemiology; D005951:Glucose Tolerance Test; D006801:Humans; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000502:physiology*; D049590:Postpartum Period / Q000097:blood / Q000502:physiology; D011247:Pregnancy; D011379:Prognosis
chemical_list: D001786:Blood Glucose