{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:52:09Z","timestamp":1787025129607,"version":"build-2736575974"},"reference-count":30,"publisher":"American Diabetes Association","issue":"4","license":[{"start":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T00:00:00Z","timestamp":1771372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJ9-192251"],"award-info":[{"award-number":["PJ9-192251"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-156286"],"award-info":[{"award-number":["PJT-156286"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["PJT-195810"],"award-info":[{"award-number":["PJT-195810"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:sec>\n                    <jats:title>OBJECTIVE<\/jats:title>\n                    <jats:p>It has been postulated that pregnancies may contribute to the lifetime risk of type 2 diabetes mellitus (T2DM) in women, although direct evidence is lacking. In this context, we hypothesized that pregnancy may impact the long-term natural history of the pathophysiologic determinants of T2DM: insulin sensitivity and \u03b2-cell function. We sought to evaluate 10-year trajectories of these features in parous women with and without an additional pregnancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESEARCH DESIGN AND METHODS<\/jats:title>\n                    <jats:p>Metabolic characterization was done in 303 women at 1 year postpartum and on three or more occasions over the decade thereafter. Each assessment included an oral glucose tolerance test, enabling serial evaluation of insulin sensitivity\/resistance (Matsuda index; HOMA-insulin resistance [IR]), \u03b2-cell function (Insulin Secretion-Sensitivity Index-2; insulinogenic index\/HOMA-IR), and glycemia. Linear mixed-effect models adjusted for diabetes risk factors were constructed to evaluate the natural time trend of these measures over 10 years in those with (n = 78) and without (n = 225) an additional pregnancy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>At baseline, women who subsequently had an additional pregnancy were younger (P &amp;lt; 0.001) and more likely to be primiparous (P &amp;lt; 0.001) than their peers. Notably, they had higher covariate-adjusted insulin sensitivity (Matsuda index) at baseline (estimated adjusted average difference 1.64; 95% CI 0.22\u20132.86) and at 1.5 years\u2019 follow-up (1.28; \u22120.15 to 2.50), but this difference disappeared by 3.5 years and 5.5 years. The 10-year trajectory of the Matsuda index differed between the groups (time-group interaction P = 0.02), with no differences in trajectories of \u03b2-cell function and glycemia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Pregnancy is associated with worsening of the long-term trajectory of insulin sensitivity, revealing both a pathophysiologic basis for enhanced diabetes risk and a target for risk modification.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/dc25-2354","type":"journal-article","created":{"date-parts":[[2026,2,18]],"date-time":"2026-02-18T16:24:42Z","timestamp":1771431882000},"page":"664-673","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":1,"title":["Impact of an Additional Pregnancy on the Natural History of Insulin Sensitivity, \u03b2-Cell Function, and Glycemia in Parous Women"],"prefix":"10.2337","volume":"49","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1989-027X","authenticated-orcid":false,"given":"Ravi","family":"Retnakaran","sequence":"first","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital 1 , Toronto, Ontario, Canada"},{"name":"Division of Endocrinology, University of Toronto 2 , Toronto, Ontario, Canada"},{"name":"Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital 3 , Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junwei","family":"Shen","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital 1 , Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Hanley","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital 1 , Toronto, Ontario, Canada"},{"name":"Department of Nutritional Sciences, University of Toronto 4 , Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernard","family":"Zinman","sequence":"additional","affiliation":[{"name":"Leadership Sinai Centre for Diabetes, Mount Sinai Hospital 1 , Toronto, Ontario, Canada"},{"name":"Division of Endocrinology, University of Toronto 2 , Toronto, Ontario, Canada"},{"name":"Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital 3 , Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2026,2,18]]},"reference":[{"key":"2026061812263078600_B1","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1001\/jama.1995.03520300035033","article-title":"Weight, weight change, and coronary heart disease in women. Risk within the \u2018normal\u2019 weight range","volume":"273","author":"Willett","year":"1995","journal-title":"JAMA"},{"key":"2026061812263078600_B2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1186\/s12933-024-02184-4","article-title":"Postpartum weight retention and the early evolution of cardiovascular risk over the first 5 years after pregnancy","volume":"23","author":"Kramer","year":"2024","journal-title":"Cardiovasc Diabetol"},{"key":"2026061812263078600_B3","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.2337\/dc06-0825","article-title":"Parity and risk of type 2 diabetes: the Atherosclerosis Risk in Communities Study","volume":"29","author":"Nicholson","year":"2006","journal-title":"Diabetes Care"},{"key":"2026061812263078600_B4","doi-asserted-by":"crossref","first-page":"1778","DOI":"10.2337\/dc10-0015","article-title":"Parity and the association with diabetes in older women","volume":"33","author":"Fowler-Brown","year":"2010","journal-title":"Diabetes Care"},{"key":"2026061812263078600_B5","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.jdiacomp.2016.10.005","article-title":"Higher parity is associated with increased risk of Type 2 diabetes mellitus in women: a linear dose-response meta-analysis of cohort studies","volume":"31","author":"Guo","year":"2017","journal-title":"J Diabetes Complications"},{"key":"2026061812263078600_B6","doi-asserted-by":"crossref","first-page":"837","DOI":"10.4093\/dmj.2024.0536","article-title":"The impact of obesity on the association between parity and risk of type 2 diabetes mellitus","volume":"49","author":"Gen","year":"2025","journal-title":"Diabetes Metab J"},{"key":"2026061812263078600_B7","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/0002-9343(92)90674-Z","article-title":"Parity and incidence of non-insulin-dependent diabetes mellitus","volume":"93","author":"Manson","year":"1992","journal-title":"Am J Med"},{"key":"2026061812263078600_B8","doi-asserted-by":"crossref","first-page":"690","DOI":"10.2337\/diacare.25.4.690","article-title":"Association of parity with risk of type 2 diabetes and related metabolic disorders","volume":"25","author":"Hanley","year":"2002","journal-title":"Diabetes Care"},{"key":"2026061812263078600_B9","doi-asserted-by":"crossref","first-page":"e000237","DOI":"10.1136\/bmjdrc-2016-000237","article-title":"Parity and type 2 diabetes mellitus: a study of insulin resistance and \u03b2-cell function in women with multiple pregnancies","volume":"4","author":"Iversen","year":"2016","journal-title":"BMJ Open Diabetes Res Care"},{"key":"2026061812263078600_B10","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1038\/s41572-019-0098-8","article-title":"Gestational diabetes mellitus","volume":"5","author":"McIntyre","year":"2019","journal-title":"Nat Rev Dis Primers"},{"key":"2026061812263078600_B11","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1016\/S2213-8587(20)30161-3","article-title":"Gestational diabetes: opportunities for improving maternal and child health","volume":"8","author":"Saravanan","year":"2020","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2026061812263078600_B12","doi-asserted-by":"crossref","first-page":"101294","DOI":"10.1016\/j.eclinm.2022.101294","article-title":"The life course perspective of gestational diabetes: an opportunity for the prevention of diabetes and heart disease in women","volume":"45","author":"Fu","year":"2022","journal-title":"EClinicalMedicine"},{"key":"2026061812263078600_B13","doi-asserted-by":"crossref","first-page":"2137","DOI":"10.2337\/dc22-2226","article-title":"Distinct insulin physiology trajectories in euglycemic pregnancy and gestational diabetes mellitus","volume":"46","author":"Thaweethai","year":"2023","journal-title":"Diabetes Care"},{"key":"2026061812263078600_B14","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/S2213-8587(23)00062-1","article-title":"Glucose intolerance in pregnancy and risk of early-onset type 2 diabetes: a population-based cohort study","volume":"11","author":"Bardugo","year":"2023","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2026061812263078600_B15","doi-asserted-by":"crossref","first-page":"2154","DOI":"10.1007\/s00125-023-05994-5","article-title":"Deteriorating beta cell function is the dominant determinant of progression from normal glucose tolerance to prediabetes\/diabetes in young women following pregnancy","volume":"66","author":"Retnakaran","year":"2023","journal-title":"Diabetologia"},{"key":"2026061812263078600_B16","doi-asserted-by":"crossref","first-page":"887","DOI":"10.2337\/dc24-1848","article-title":"One-hour oral glucose tolerance test for the postpartum reclassification of women with hyperglycemia in pregnancy","volume":"48","author":"Retnakaran","year":"2025","journal-title":"Diabetes Care"},{"key":"2026061812263078600_B17","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/S2213-8587(25)00163-9","article-title":"The central role of recovery of \u03b2-cell function in the remission of prediabetes: a prospective cohort study in Canada","volume":"13","author":"Retnakaran","year":"2025","journal-title":"Lancet Diabetes Endocrinol"},{"key":"2026061812263078600_B18","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1093\/ajcn\/36.5.936","article-title":"A short questionnaire for the measurement of habitual physical activity in epidemiological studies","volume":"36","author":"Baecke","year":"1982","journal-title":"Am J Clin Nutr"},{"key":"2026061812263078600_B19","first-page":"S1","article-title":"A collection of Physical Activity Questionnaires for health-related research","volume":"29","author":"Pereira","year":"1997","journal-title":"Med Sci Sports Exerc"},{"key":"2026061812263078600_B20","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1016\/j.jcjd.2017.10.003","article-title":"Definition, classification and diagnosis of diabetes, prediabetes and metabolic syndrome","volume":"42","author":"Punthakee","year":"2018","journal-title":"Can J Diabetes"},{"key":"2026061812263078600_B21","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.2337\/diacare.22.9.1462","article-title":"Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp","volume":"22","author":"Matsuda","year":"1999","journal-title":"Diabetes Care"},{"key":"2026061812263078600_B22","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"2026061812263078600_B23","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1038\/oby.2008.307","article-title":"Hyperbolic relationship between insulin secretion and sensitivity on oral glucose tolerance test","volume":"16","author":"Retnakaran","year":"2008","journal-title":"Obesity (Silver Spring)"},{"key":"2026061812263078600_B24","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1111\/j.1464-5491.2009.02841.x","article-title":"Evaluation of proposed oral disposition index measures in relation to the actual disposition index","volume":"26","author":"Retnakaran","year":"2009","journal-title":"Diabet Med"},{"key":"2026061812263078600_B25","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.3945\/ajcn.110.008326","article-title":"Associations of gestational weight gain with maternal body mass index, waist circumference, and blood pressure measured 16 y after pregnancy: the Avon Longitudinal Study of Parents and Children (ALSPAC)","volume":"93","author":"Fraser","year":"2011","journal-title":"Am J Clin Nutr"},{"key":"2026061812263078600_B26","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1002\/oby.22736","article-title":"Increased visceral adipose tissue without weight retention at 59 weeks postpartum","volume":"28","author":"Janumala","year":"2020","journal-title":"Obesity (Silver Spring)"},{"key":"2026061812263078600_B27","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1093\/epirev\/mxt006","article-title":"Pregnancy characteristics and women\u2019s future cardiovascular health: an underused opportunity to improve women\u2019s health?","volume":"36","author":"Rich-Edwards","year":"2014","journal-title":"Epidemiol Rev"},{"key":"2026061812263078600_B28","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1056\/NEJMp1806516","article-title":"Postpartum care in the United States \u2014 new policies for a new paradigm","volume":"379","author":"Murray Horwitz","year":"2018","journal-title":"N Engl J Med"},{"key":"2026061812263078600_B29","first-page":"CD005627","article-title":"Diet or exercise, or both, for weight reduction in women after childbirth","volume":"2013","author":"Amorim Adegboye","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"2026061812263078600_B30","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1016\/j.numecd.2021.07.025","article-title":"Changes in adiposity mediate the associations of diet quality with insulin sensitivity and beta-cell function","volume":"31","author":"Lai","year":"2021","journal-title":"Nutr Metab Cardiovasc Dis"}],"container-title":["Diabetes Care"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/49\/4\/664\/857327\/dc252354.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/diabetesjournals.org\/care\/article-pdf\/49\/4\/664\/857327\/dc252354.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T16:26:40Z","timestamp":1781800000000},"score":1,"resource":{"primary":{"URL":"https:\/\/diabetesjournals.org\/care\/article\/49\/4\/664\/164501\/Impact-of-an-Additional-Pregnancy-on-the-Natural"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,18]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,2,18]]},"published-print":{"date-parts":[[2026,4,1]]}},"URL":"https:\/\/doi.org\/10.2337\/dc25-2354","relation":{},"ISSN":["0149-5992","1935-5548"],"issn-type":[{"value":"0149-5992","type":"print"},{"value":"1935-5548","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,18]]}}}