title: History of infertility and risk of type 2 diabetes mellitus: a prospective cohort study.
abstract: OBJECTIVE
  We sought to evaluate the relationship between delayed conception and type 2 diabetes risk, given that there are plausible underlying mechanisms linking the two, including inflammation and insulin resistance.
  
  
  METHODS
  Participants of the Nurses' Health Study II prospective cohort were included if they were free of chronic disease (cardiovascular disease, type 2 diabetes, cancer) at baseline. Biennial questionnaires updated information on infertility status (>12 months attempted pregnancy), lifestyle characteristics and several health-related outcomes. Self-reported cases of diabetes were confirmed using a follow-up questionnaire. Multivariable Cox proportional hazards models were used to compute the HRs and 95% CIs.
  
  
  RESULTS
  Incident type 2 diabetes occurred in 5,993 of the 112,106 participants over 24 years of follow-up (1989-2013). A history of infertility was reported in 27,774 (24.8%) women and was associated with a 20% greater risk of developing diabetes, compared with those never reporting infertility (HR 1.20 [95% CI 1.14, 1.28]), after adjusting for age, lifestyle factors, marital status, oral contraceptive use, family history of diabetes and BMI. Compared with women without a history of infertility, the causes of infertility associated with a higher diabetes risk were ovulation disorders (HR 1.43 [95% CI 1.29, 1.58]) and tubal factor (HR 1.34 [95% CI 1.13, 1.58]). Cervical factor (HR 1.06 [95% CI 0.81, 1.40]) and endometriosis (HR 1.06 [95% CI 0.89, 1.27]) were not associated, while male factor infertility was associated with a modestly higher diabetes risk (HR 1.15 [95% CI 1.00, 1.33]).
  
  
  CONCLUSIONS
  These novel findings suggest a history of infertility, particularly that related to ovulation disorders and tubal blockage, is significantly associated with a higher risk of type 2 diabetes.
authors.affiliation: Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 900 Commonwealth Avenue, Boston, MA, 02215, USA, dtobias@partners.org.
authors.forename: Deirdre K
authors.initials: DK
authors.lastname: Tobias
authors.forename: Audrey J
authors.initials: AJ
authors.lastname: Gaskins
authors.forename: Stacey A
authors.initials: SA
authors.lastname: Missmer
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.forename: Germaine M
authors.initials: GM
authors.lastname: Buck Louis
authors.forename: Cuilin
authors.initials: C
authors.lastname: Zhang
authors.forename: Jorge E
authors.initials: JE
authors.lastname: Chavarro
mesh_terms: D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000453:epidemiology*; D005260:Female; D005298:Fertility; D006306:Health Surveys; D006801:Humans; D015994:Incidence; D007247:Infertility, Female / Q000175:diagnosis / Q000453:epidemiology* / Q000503:physiopathology; D007248:Infertility, Male / Q000453:epidemiology / Q000503:physiopathology; D008137:Longitudinal Studies; D008297:Male; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires; D013997:Time Factors; D014481:United States / Q000453:epidemiology; D055815:Young Adult