{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,21]],"date-time":"2026-10-21T08:21:07Z","timestamp":1792570867587,"version":"4.5.0"},"reference-count":19,"publisher":"American Diabetes Association","issue":"9","license":[{"start":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T00:00:00Z","timestamp":1718236800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK TR000135"],"award-info":[{"award-number":["DK TR000135"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK116231"],"award-info":[{"award-number":["DK116231"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK126206"],"award-info":[{"award-number":["DK126206"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["DK78646"],"award-info":[{"award-number":["DK78646"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,9,1]]},"abstract":"<jats:sec>\n                  <jats:title\/>\n                  <jats:p>The T allele at rs7903146 in TCF7L2 increases the rate of conversion from prediabetes to type 2 diabetes. This has been associated with impaired \u03b2-cell function and with defective suppression of \u03b1-cell secretion by glucose. However, the temporal relationship of these abnormalities is uncertain. To study the longitudinal changes in islet function, we recruited 128 subjects, with 67 homozygous for the diabetes-associated allele (TT) at rs7903146 and 61 homozygous for the protective allele. Subjects were studied on two occasions, 3 years apart, using an oral 75-g glucose challenge. The oral minimal model was used to quantitate \u03b2-cell function; the glucagon secretion rate was estimated from deconvolution of glucagon concentrations. Glucose tolerance worsened in subjects with the TT genotype. This was accompanied by impaired postchallenge glucagon suppression but appropriate \u03b2-cell responsivity to rising glucose concentrations. These data suggest that \u03b1-cell abnormalities associated with the TT genotype (rs7903146) occur early and may precede \u03b2-cell dysfunction in people as they develop glucose intolerance and type 2 diabetes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Article Highlights<\/jats:title>\n               <\/jats:sec>","DOI":"10.2337\/db24-0192","type":"journal-article","created":{"date-parts":[[2024,6,13]],"date-time":"2024-06-13T14:20:57Z","timestamp":1718288457000},"page":"1440-1446","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":11,"title":["The Longitudinal Effect of Diabetes-Associated Variation in <i>TCF7L2<\/i> on Islet Function in Humans"],"prefix":"10.2337","volume":"73","author":[{"given":"Maya","family":"Zeini","sequence":"first","affiliation":[{"name":"1Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcello C.","family":"Laurenti","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0379-9279","authenticated-orcid":false,"given":"Aoife M.","family":"Egan","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalpana","family":"Muthusamy","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anisha","family":"Ramar","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Vella","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent R.","family":"Bailey","sequence":"additional","affiliation":[{"name":"2Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0169-6682","authenticated-orcid":false,"given":"Claudio","family":"Cobelli","sequence":"additional","affiliation":[{"name":"3Department of Women and Children\u2019s Health, University of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4908-0596","authenticated-orcid":false,"given":"Chiara","family":"Dalla Man","sequence":"additional","affiliation":[{"name":"4Department of Information Engineering, University of Padova, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6493-7837","authenticated-orcid":false,"given":"Adrian","family":"Vella","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology, Diabetes & Metabolism, Mayo Clinic College of Medicine, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2024,6,13]]},"reference":[{"key":"2024082018504145800_B1","doi-asserted-by":"crossref","first-page":"1505","DOI":"10.1038\/s41588-018-0241-6","article-title":"Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps","volume":"50","author":"Mahajan","year":"2018","journal-title":"Nat 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