title: Evaluation of Circulating Determinants of Beta-Cell Function in Women With and Without Gestational Diabetes.
abstract: Gestational diabetes (GDM) arises in women in whom there is insufficient β-cell compensation for the insulin resistance of late pregnancy. The mechanisms underlying both normal antepartum β-cell adaptation and its aberrancy in GDM are unclear. Preclinical studies have suggested that the hormones prolactin and human placental lactogen (HPL) may stimulate β-cell mass, whereas the furan fatty acid metabolite 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) has recently emerged as a potential negative regulator of β-cell function. However, there has been limited study of these factors in humans.
  
  
  
  Our objective was to systematically evaluate HPL, prolactin, and CMPF in relation to glucose homeostasis and β-cell function in women with and without GDM.
  
  
  
  Three-hundred-and-ninety-five women underwent an oral glucose tolerance test in late pregnancy, enabling assessment of GDM status, glycemia (area-under-the-glucose-curve on oral glucose tolerance test [AUCglucose]), β-cell function (Insulin Secretion-Sensitivity Index-2, insulinogenic index/homeostatic model assessment of insulin resistance [HOMA-IR]), insulin sensitivity/resistance (Matsuda index, HOMA-IR), and circulating HPL, prolactin, and CMPF.
  
  
  
  Serum concentrations of HPL, prolactin, and CMPF were similar between women with GDM (n = 105) and women without GDM (n = 290). However, on multiple linear regression analyses, CMPF emerged as a significant predictor of AUCglucose in women with GDM (t = 4.75, P < .0001) but not in their peers (P = .60). Furthermore, CMPF independently predicted lower Insulin Secretion-Sensitivity Index-2 (t = -2.28, P = .02) and lower insulinogenic index/HOMA-IR (t = -2.22, P = .03) in women with GDM but not in the non-GDM group (both P = .93). Neither HPL nor prolactin was significantly associated with AUCglucose, β-cell function, or insulin sensitivity.
  
  
  
  CMPF is a potential circulating determinant of β-cell dysfunction and hyperglycemia in women with GDM.
authors.affiliation: Leadership Sinai Centre for Diabetes (R.R., C.Y., C.K.K., A.J.H., B.Z.), Mt Sinai Hospital, Toronto, Ontario, Canada; Division of Endocrinology (R.R., C.K.K., P.W.C., A.J.H., B.Z.), University of Toronto, Toronto, Ontario, Canada; Lunenfeld-Tanenbaum Research Institute (R.R., B.Z.), Mt Sinai Hospital, Toronto, Canada; Keenan Research Centre for Biomedical Science of St. Michael's Hospital (P.W.C.), Toronto, Canada; Department of Nutritional Sciences (A.J.H.), University of Toronto, Toronto, Ontario, Canada; and Division of Obstetrics and Gynecology (M.S.), Mt Sinai Hospital, Toronto, Canada.
authors.forename: Ravi
authors.initials: R
authors.lastname: Retnakaran
authors.affiliation: Leadership Sinai Centre for Diabetes (R.R., C.Y., C.K.K., A.J.H., B.Z.), Mt Sinai Hospital, Toronto, Ontario, Canada; Division of Endocrinology (R.R., C.K.K., P.W.C., A.J.H., B.Z.), University of Toronto, Toronto, Ontario, Canada; Lunenfeld-Tanenbaum Research Institute (R.R., B.Z.), Mt Sinai Hospital, Toronto, Canada; Keenan Research Centre for Biomedical Science of St. Michael's Hospital (P.W.C.), Toronto, Canada; Department of Nutritional Sciences (A.J.H.), University of Toronto, Toronto, Ontario, Canada; and Division of Obstetrics and Gynecology (M.S.), Mt Sinai Hospital, Toronto, Canada.
authors.forename: Chang
authors.initials: C
authors.lastname: Ye
authors.affiliation: Leadership Sinai Centre for Diabetes (R.R., C.Y., C.K.K., A.J.H., B.Z.), Mt Sinai Hospital, Toronto, Ontario, Canada; Division of Endocrinology (R.R., C.K.K., P.W.C., A.J.H., B.Z.), University of Toronto, Toronto, Ontario, Canada; Lunenfeld-Tanenbaum Research Institute (R.R., B.Z.), Mt Sinai Hospital, Toronto, Canada; Keenan Research Centre for Biomedical Science of St. Michael's Hospital (P.W.C.), Toronto, Canada; Department of Nutritional Sciences (A.J.H.), University of Toronto, Toronto, Ontario, Canada; and Division of Obstetrics and Gynecology (M.S.), Mt Sinai Hospital, Toronto, Canada.
authors.forename: Caroline K
authors.initials: CK
authors.lastname: Kramer
authors.affiliation: Leadership Sinai Centre for Diabetes (R.R., C.Y., C.K.K., A.J.H., B.Z.), Mt Sinai Hospital, Toronto, Ontario, Canada; Division of Endocrinology (R.R., C.K.K., P.W.C., A.J.H., B.Z.), University of Toronto, Toronto, Ontario, Canada; Lunenfeld-Tanenbaum Research Institute (R.R., B.Z.), Mt Sinai Hospital, Toronto, Canada; Keenan Research Centre for Biomedical Science of St. Michael's Hospital (P.W.C.), Toronto, Canada; Department of Nutritional Sciences (A.J.H.), University of Toronto, Toronto, Ontario, Canada; and Division of Obstetrics and Gynecology (M.S.), Mt Sinai Hospital, Toronto, Canada.
authors.forename: Philip W
authors.initials: PW
authors.lastname: Connelly
authors.affiliation: Leadership Sinai Centre for Diabetes (R.R., C.Y., C.K.K., A.J.H., B.Z.), Mt Sinai Hospital, Toronto, Ontario, Canada; Division of Endocrinology (R.R., C.K.K., P.W.C., A.J.H., B.Z.), University of Toronto, Toronto, Ontario, Canada; Lunenfeld-Tanenbaum Research Institute (R.R., B.Z.), Mt Sinai Hospital, Toronto, Canada; Keenan Research Centre for Biomedical Science of St. Michael's Hospital (P.W.C.), Toronto, Canada; Department of Nutritional Sciences (A.J.H.), University of Toronto, Toronto, Ontario, Canada; and Division of Obstetrics and Gynecology (M.S.), Mt Sinai Hospital, Toronto, Canada.
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hanley
authors.affiliation: Leadership Sinai Centre for Diabetes (R.R., C.Y., C.K.K., A.J.H., B.Z.), Mt Sinai Hospital, Toronto, Ontario, Canada; Division of Endocrinology (R.R., C.K.K., P.W.C., A.J.H., B.Z.), University of Toronto, Toronto, Ontario, Canada; Lunenfeld-Tanenbaum Research Institute (R.R., B.Z.), Mt Sinai Hospital, Toronto, Canada; Keenan Research Centre for Biomedical Science of St. Michael's Hospital (P.W.C.), Toronto, Canada; Department of Nutritional Sciences (A.J.H.), University of Toronto, Toronto, Ontario, Canada; and Division of Obstetrics and Gynecology (M.S.), Mt Sinai Hospital, Toronto, Canada.
authors.forename: Mathew
authors.initials: M
authors.lastname: Sermer
authors.affiliation: Leadership Sinai Centre for Diabetes (R.R., C.Y., C.K.K., A.J.H., B.Z.), Mt Sinai Hospital, Toronto, Ontario, Canada; Division of Endocrinology (R.R., C.K.K., P.W.C., A.J.H., B.Z.), University of Toronto, Toronto, Ontario, Canada; Lunenfeld-Tanenbaum Research Institute (R.R., B.Z.), Mt Sinai Hospital, Toronto, Canada; Keenan Research Centre for Biomedical Science of St. Michael's Hospital (P.W.C.), Toronto, Canada; Department of Nutritional Sciences (A.J.H.), University of Toronto, Toronto, Ontario, Canada; and Division of Obstetrics and Gynecology (M.S.), Mt Sinai Hospital, Toronto, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Zinman
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000032:analysis / Q000097:blood*; D001786:Blood Glucose / Q000378:metabolism; D016022:Case-Control Studies; D016640:Diabetes, Gestational / Q000097:blood* / Q000503:physiopathology; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000378:metabolism / Q000502:physiology*; D011247:Pregnancy
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007328:Insulin