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Women carrying\n                      <jats:italic>BRCA<\/jats:italic>\n                      likely pathogenic\/pathogenic variants (LP\/PV) are at increased risk of premature menopause and may therefore be at higher risk of developing metabolic disorders later in life. In this single-center prospective cohort study, we investigated whether the specific\n                      <jats:italic>BRCA<\/jats:italic>\n                      mutation (\n                      <jats:italic>BRCA<\/jats:italic>\n                      1 vs.\n                      <jats:italic>BRCA<\/jats:italic>\n                      2) has a differential impact on metabolism in women.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Eligible participants were\n                      <jats:italic>BRCA<\/jats:italic>\n                      LP\/PV carriers who were premenopausal or underwent menopause \u2013either natural or iatrogenic\u2013 within the 5 years prior to enrollment. Blood samples for lipid and glucose panels were obtained every 6 months, for a total of four time points. Body composition variables were evaluated at baseline and at the final follow-up using bioimpedance analysis. Glucose tolerance was assessed using the homeostatic model assessment for insulin resistance (HOMA-IR). Associations between lipid and glucose profile and patient characteristics were evaluated using univariable and multivariable linear regression models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Fifty-seven BRCA1 and 58 BRCA2 LP\/PV carriers were included in the final analysis. At baseline,\n                      <jats:italic>BRCA1<\/jats:italic>\n                      LP\/PV carriers had a higher body mass index (BMI) (27.3 vs. 24.6\u00a0kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01) and higher fat mass (27.3 vs. 21.9\u00a0kg,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.013) than\n                      <jats:italic>BRCA2<\/jats:italic>\n                      LP\/PV carriers. Insulin levels and HOMA-IR were consistently higher in\n                      <jats:italic>BRCA1<\/jats:italic>\n                      than in\n                      <jats:italic>BRCA2<\/jats:italic>\n                      LP\/PV carriers at all time points, and this difference was not attributable to age, BMI, menopausal status, risk-reducing salpingo-oophorectomy, previous chemotherapy or use of cholesterol-lowering agents. The lipid profile was similar between the groups, although\n                      <jats:italic>BRCA1<\/jats:italic>\n                      LP\/PV carriers showed a tendency toward a less favorable profile (higher LDL and lower HDL).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These prospective results suggest that\n                      <jats:italic>BRCA1<\/jats:italic>\n                      LP\/PV carriers might have impaired glucose tolerance and a greater tendency toward insulin resistance compared with\n                      <jats:italic>BRCA2<\/jats:italic>\n                      LP\/PV carriers: this first report needs further independent confirmations from other cohorts.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10689-026-00570-3","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T07:05:22Z","timestamp":1778742322000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impaired glucose tolerance in women with BRCA1 versus BRCA2 pathogenic or likely pathogenic variants: Results from a prospective cohort study"],"prefix":"10.1007","volume":"25","author":[{"given":"Giovanni","family":"Grandi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Piombino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Sighinolfi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Barbieri","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Venturelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Melotti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Lippi Bruni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentina","family":"Grisendi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Cuoghi Costantini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mina","family":"Grippa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emma","family":"Zattarin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Tenedini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elisabetta","family":"Razzaboni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giulia","family":"Brigante","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roberto","family":"D\u2019Amico","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benedetta","family":"Nanni","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Renata","family":"Menozzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Cortesi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Dominici","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"La Marca","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Toss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"issue":"23","key":"570_CR1","doi-asserted-by":"publisher","first-page":"2402","DOI":"10.1001\/jama.2017.7112","volume":"20","author":"KB Kuchenbaecker","year":"2017","unstructured":"Kuchenbaecker KB, Hopper JL, Barnes DR, Phillips K-A, Mooij TM, Roos-Blom M-J et al (2017) Risks of Breast, Ovarian, and Contralateral Breast Cancer for BRCA1 and BRCA2 Mutation Carriers. 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