title: Women with prior gestational diabetes mellitus and prediabetes are characterised by a decreased incretin effect.
abstract: We investigated whether a reduced incretin effect, as observed in patients with type 2 diabetes, can be detected in high-risk individuals, such as women with prior gestational diabetes mellitus (pGDM).
  
  
  
  In this cross-sectional study, 102 women without diabetes with pGDM and 15 control participants without pGDM and with normal glucose tolerance (NGT) underwent a 4 h 75 g OGTT and an isoglycaemic i.v. glucose infusion (IIGI). Women with pGDM were classified as having NGT or prediabetes (impaired fasting glucose and/or impaired glucose tolerance). Insulin sensitivity was assessed using the Matsuda index and HOMA2-IR and the incretin effect was calculated from insulin responses during the study (100% × [AUCinsulin,OGTT- AUCinsulin,IIGI]/AUCinsulin,OGTT).
  
  
  
  Sixty-three of the 102 women with pGDM (62%) had prediabetes (median [interquartile range]: age, 38.3 [6.5] years; BMI, 32.1 [5.8] kg/m2) and 39 women (38%) had NGT (age, 39.5 [5.6] years; BMI, 31.0 [6.7] kg/m2). Control participants (n = 15) were not significantly different from the pGDM group with regards to age (39.2 [7.4] years) and BMI (28.8 [9.2] kg/m2). Compared with women with NGT and control participants, women with prediabetes had lower insulin sensitivity, as measured by the Matsuda index (3.0 [2.4] vs 5.0 [2.6] vs 1.5 [1.8], respectively; p < 0.001). The incretin effect was 55.3% [27.8], 73.8% [19.0] and 76.7% [24.6] in women with prediabetes, women with normal glucose tolerance and control participants, respectively (p < 0.01).
  
  
  
  Prediabetes was highly prevalent in women with pGDM, and alterations in the incretin effect were detected in this group before the development of type 2 diabetes.
  
  
  
  clinicaltrialsregister.eu 2012-001371-37-DK.
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900, Hellerup, Denmark.|NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Danish Diabetes Academy, Odense University Hospital, Odense, Denmark.
authors.forename: Signe
authors.initials: S
authors.lastname: Foghsgaard
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900, Hellerup, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Vedtofte
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900, Hellerup, Denmark.
authors.forename: Camilla
authors.initials: C
authors.lastname: Andreasen
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900, Hellerup, Denmark.
authors.forename: Emilie S
authors.initials: ES
authors.lastname: Andersen
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900, Hellerup, Denmark.
authors.forename: Emilie
authors.initials: E
authors.lastname: Bahne
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900, Hellerup, Denmark.
authors.forename: Jonatan I
authors.initials: JI
authors.lastname: Bagger
authors.affiliation: Department of Gynecology and Obstetrics, Herlev Hospital, Herlev, Denmark.
authors.forename: Jens A
authors.initials: JA
authors.lastname: Svare
authors.affiliation: NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Department of Gynecology and Obstetrics, Nordsjællands Hospital, Hillerød, Denmark.
authors.forename: Tine D
authors.initials: TD
authors.lastname: Clausen
authors.affiliation: Center for Pregnant Women with Diabetes, Department of Endocrinology, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Elisabeth R
authors.initials: ER
authors.lastname: Mathiesen
authors.affiliation: Center for Pregnant Women with Diabetes, Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Peter
authors.initials: P
authors.lastname: Damm
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900, Hellerup, Denmark.|NNF Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Filip K
authors.initials: FK
authors.lastname: Knop
authors.affiliation: Center for Diabetes Research, Gentofte Hospital, University of Copenhagen, Kildegårdsvej 28, DK-2900, Hellerup, Denmark. t.vilsboll@dadlnet.dk.|Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. t.vilsboll@dadlnet.dk.
authors.forename: Tina
authors.initials: T
authors.lastname: Vilsbøll
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003718:Denmark; D003924:Diabetes Mellitus, Type 2; D016640:Diabetes, Gestational / Q000097:blood* / Q000503:physiopathology*; D004311:Double-Blind Method; D005260:Female; D005934:Glucagon / Q000032:analysis; D052216:Glucagon-Like Peptide 1 / Q000032:analysis; D005951:Glucose Tolerance Test; D006801:Humans; D054795:Incretins / Q000097:blood*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D011236:Prediabetic State / Q000097:blood* / Q000503:physiopathology*; D011247:Pregnancy; D015995:Prevalence
chemical_list: D001786:Blood Glucose; D054795:Incretins; D007328:Insulin; D052216:Glucagon-Like Peptide 1; D005934:Glucagon
keywords: Gestational diabetes mellitus; Impaired glucose tolerance; Incretin effect; Isoglycaemic i.v. glucose infusion; Oral glucose tolerance test; Prediabetes; Type 2 diabetes