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We used Cox proportional hazard models to estimate the HR and 95% CI of type 2 diabetes and adjusted for a priori potential confounding variables. Person-time was stratified a priori by age (\u226450 and &gt;50 years); in secondary analyses, we restricted the sample to those with a BMI of &lt;25 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      at 18 years of age. We used linear regression models to assess the prospective association between the history of infertility and log-transformed blood HbA\n                      <jats:sub>1c<\/jats:sub>\n                      concentrations measured on average at age 44, among a subset of participants with this measure (\n                      <jats:italic>n<\/jats:italic>\n                      =2399).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The association between a history of infertility and the risk of type 2 diabetes differed before and after the age of 50 (\n                      <jats:italic>p<\/jats:italic>\n                      value, test for interaction: 0.0004). Up to 50 years of age, infertility history was associated with a 32% greater risk of type 2 diabetes (95% CI 1.22, 1.43); for specific infertility diagnoses, ovulatory disorders were associated with a 67% greater risk (95% CI 1.48, 1.89), whereas tubal blockage (HR 1.29 [95% CI 1.01, 1.64]), male factor infertility (HR 1.30 [95% CI 1.08, 1.57]) and \u2018cause not found\u2019 (HR 1.26 [95% CI 1.05, 1.51]) were all associated with a ~30% greater risk of type 2 diabetes. After the age of 50, the association between overall infertility and type 2 diabetes attenuated (HR 1.12 [95% CI 1.06, 1.19]), as did associations between ovulatory disorders and type 2 diabetes (HR 1.18 [95% CI 1.05, 1.32]). The association between tubal blockage and the risk of type 2 diabetes remained similar after the age of 50 (HR 1.26 [95% CI 1.05, 1.51]). The overall association between infertility and the risk of type 2 diabetes remained elevated among women with a BMI of &lt;25 kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      at the age of 18 (\u226450 years, HR 1.32 [95% CI 1.20, 1.44]; &gt;50 years, HR 1.11 [95% CI 1.04, 1.19]). Women with a history of infertility also had slightly higher mean HbA\n                      <jats:sub>1c<\/jats:sub>\n                      levels than women without a history of infertility (relative difference: 0.7% [95% CI 0.04, 1.32]), reflecting a minimal absolute difference in HbA\n                      <jats:sub>1c<\/jats:sub>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\/interpretation<\/jats:title>\n                    <jats:p>Women with a history of infertility had a greater risk of developing type 2 diabetes, particularly prior to the age of 51 years. Specific reasons for infertility were associated with an elevated type 2 diabetes risk, including ovulatory disorders and tubal factors. These associations were independent of BMI.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00125-026-06784-5","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T23:49:23Z","timestamp":1782863363000},"page":"2523-2533","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["History of infertility, risk of type 2 diabetes and HbA1c levels in the Nurses\u2019 Health Study II"],"prefix":"10.1007","volume":"69","author":[{"given":"Leslie V.","family":"Farland","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"William J.","family":"Degnan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siwen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey J.","family":"Gaskins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge E.","family":"Chavarro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet W.","family":"Rich-Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deirdre K.","family":"Tobias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stacey A.","family":"Missmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,30]]},"reference":[{"issue":"5","key":"6784_CR1","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1016\/j.fertnstert.2012.11.037","volume":"99","author":"ME Thoma","year":"2013","unstructured":"Thoma ME, McLain AC, Louis JF et al (2013) Prevalence of infertility in the United States as estimated by the current duration approach and a traditional constructed approach. 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Because of participant confidentiality and privacy concerns, data cannot be shared publicly. According to standardised controlled access procedures, requests to access NHSII data must be submitted in writing. Applications to use NHSII resources will be reviewed by our External Collaborations Committee to verify that the proposed use maintains the protection of the privacy of participants and the confidentiality of the data. Investigators wishing to use NHSII data can find instructions for access at\n                      \n                      (contact email: nhsaccess@channing.harvard.edu), which includes submission of a brief description of the investigators\u2019 proposed project aim.","order":2,"name":"Ethics","label":"Data availability","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"This work was supported by grants HD096033, U01 CA176726 and U01 HL145386. SW was supported by the Irene M. & Fredrick J. Stare Nutrition Education Fund Doctoral Scholarship and the Mayer Fund Doctoral Scholarship. Through acceptance of this federal funding, NIH has been given a right to make this manuscript publicly available in PubMed Central upon the Official Date of publication, as defined by NIH.","order":3,"name":"Ethics","label":"Funding","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"The authors declare that there are no relationships or activities that might bias, or be perceived to bias, their work.","order":4,"name":"Ethics","label":"Authors\u2019 relationships and activities","group":{"name":"EthicsHeading","label":"Ethics"}},{"value":"LVF and SAM conceived, designed and supervised the study. WJD performed the statistical analysis. LVF, WJD, SW, AJG, JEC, JWR-E, DKT and SAM substantially contributed to the interpretation of the data, drafted and critically reviewed the manuscript, and approved the final version. LVF is the guarantor of this work.","order":5,"name":"Ethics","label":"Contribution statement","group":{"name":"EthicsHeading","label":"Ethics"}}]}}