title: Adiponectin and beta cell dysfunction in gestational diabetes: pathophysiological implications.
abstract: OBJECTIVE
  Gestational diabetes mellitus (GDM) identifies a population of young women at high risk of developing type 2 diabetes and thus provides an excellent model for studying early events in the natural history of this disease. Adiponectin, a novel adipocyte-derived protein with insulin-sensitising properties, has been proposed as a factor linking insulin resistance and beta cell dysfunction in the pathogenesis of type 2 diabetes. We conducted the current investigation to determine whether adiponectin is associated with beta cell dysfunction in GDM.
  
  
  METHODS
  We studied 180 women undergoing OGTT in late pregnancy. Based on the OGTT results, participants were stratified into three groups: (1) NGT (n=93); (2) IGT (n=39); and (3) GDM (n=48). First-phase insulin secretion was determined using a validated index previously proposed by Stumvoll. Insulin sensitivity was assessed using the validated OGTT insulin sensitivity index of Matsuda and DeFronzo (IS(OGTT)).
  
  
  RESULTS
  To evaluate beta cell function in relation to ambient insulin sensitivity, an insulin secretion-sensitivity index (ISSI) was derived from the product of the Stumvoll index and the IS(OGTT), based on the existence of the predicted hyperbolic relationship between these two measures. Mean ISSI was highest in the NGT group (6,731), followed by that in the IGT group (4,976) and then that in the GDM group (3,300) (overall p<0.0001), compatible with the notion of declining beta cell function across these glucose tolerance groups. Importantly, adiponectin was significantly correlated with ISSI (r=0.34, p<0.0001), with a stepwise increase in mean ISSI observed per tertile of adiponectin concentration (trend p<0.0001). In multivariate linear regression analysis, ISSI was positively correlated with adiponectin and negatively correlated with GDM, IGT and C-reactive protein (r(2)=0.54).
  
  
  CONCLUSIONS
  Adiponectin concentration is an independent correlate of beta cell function in late pregnancy. As such, adiponectin may play a key role in mediating insulin resistance and beta cell dysfunction in the pathogenesis of diabetes.
authors.affiliation: Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Retnakaran
authors.forename: A J G
authors.initials: AJ
authors.lastname: Hanley
authors.forename: N
authors.initials: N
authors.lastname: Raif
authors.forename: C R
authors.initials: CR
authors.lastname: Hirning
authors.forename: P W
authors.initials: PW
authors.lastname: Connelly
authors.forename: M
authors.initials: M
authors.lastname: Sermer
authors.forename: S E
authors.initials: SE
authors.lastname: Kahn
authors.forename: B
authors.initials: B
authors.lastname: Zinman
mesh_terms: D052242:Adiponectin; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D016640:Diabetes, Gestational / Q000097:blood / Q000503:physiopathology*; D005215:Fasting; D005260:Female; D005865:Gestational Age; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood*; D007515:Islets of Langerhans / Q000378:metabolism / Q000503:physiopathology*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third
chemical_list: D052242:Adiponectin; D001786:Blood Glucose; D007328:Insulin; D036341:Intercellular Signaling Peptides and Proteins