title: Effect of subsequent pregnancies on the risk of developing diabetes following a first pregnancy complicated by gestational diabetes: a population-based study.
abstract: OBJECTIVE
  Women with gestational diabetes mellitus have a high risk of developing Type 2 diabetes, secondary to post-partum progression of the chronic pancreatic ß-cell defect that underlies their presenting with dysglycaemia in pregnancy. Insulin-sensitizing therapy can decrease this risk of Type 2 diabetes, partly by offloading the secretory demand placed on the ß-cells. Conversely, however, it is not known whether the considerable secretory demands posed by the physiologic insulin resistance of a subsequent pregnancy could accelerate the progression to Type 2 diabetes. Thus, we sought to determine whether subsequent pregnancies are associated with the risk of developing diabetes following gestational diabetes.
  
  
  METHODS
  Using a population-based administrative database, we identified all women in Ontario, Canada, whose first pregnancy was between April 2000 and March 2007 and was complicated by gestational diabetes (n = 16,817). This cohort was followed for a median 4.5 years for subsequent pregnancies and the development of diabetes.
  
  
  RESULTS
  During follow-up, 2731 women (16.2%) developed diabetes. Gestational diabetes recurred in 41.5% of subsequent pregnancies. Interestingly, after covariate adjustment, a subsequent pregnancy was associated with a reduced risk of diabetes (adjusted hazard ratio (HR) = 0.68, 95%CI 0.60-0.76; P < 0.0001). Specifically, whereas each subsequent gestational diabetes pregnancy was associated with a modestly increased risk of diabetes (adjusted HR = 1.16, 95%CI 1.01-1.34; P = 0.03), each non-gestational diabetes pregnancy was associated with a significantly reduced risk of diabetes (adjusted HR=0.34, 95%CI 0.27-0.41; P < 0.0001).
  
  
  CONCLUSIONS
  A subsequent pregnancy is not necessarily associated with an increased risk of Type 2 diabetes following gestational diabetes. Instead, the absence of recurrent gestational diabetes in a subsequent pregnancy may identify a lessened risk of developing Type 2 diabetes in this high-risk patient population.
authors.affiliation: Department of Medicine Institute of Medical Science, University of Toronto Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Retnakaran
authors.forename: P C
authors.initials: PC
authors.lastname: Austin
authors.forename: B R
authors.initials: BR
authors.lastname: Shah
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000453:epidemiology* / Q000209:etiology; D016640:Diabetes, Gestational / Q000188:drug therapy / Q000453:epidemiology*; D005193:Family Planning Services; D005260:Female; D020073:Gravidity / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000627:therapeutic use*; D007333:Insulin Resistance; D009864:Ontario / Q000453:epidemiology; D011247:Pregnancy; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D007328:Insulin