{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T00:44:14Z","timestamp":1771461854247,"version":"3.50.1"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"3","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:sec>\n<jats:title><jats:italic>Objective:<\/jats:italic><\/jats:title>\n<jats:p>Determining the factors associated with new-onset pre-diabetes and type 2 diabetes mellitus (T2D) is important for improving the current prevention strategies and for a better understanding of the disease.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title><jats:italic>Design:<\/jats:italic><\/jats:title>\n<jats:p>To study the factors (clinical, circulating protein and genetic) associated with new onset pre-diabetes and T2D in an initially healthy (without diabetes) populational familial cohort with a long follow-up (STANISLAS cohort).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title><jats:italic>Methods:<\/jats:italic><\/jats:title>\n<jats:p>A total of 1506 participants attended both the visit 1 and visit 4, separated by \u224820 years. Over 400 proteins, GWAS and genetic associations were studied using models adjusted for potential confounders. Both prospective (V1 to V4) and cross-sectional (V4) analyses were performed.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title><jats:italic>Results:<\/jats:italic><\/jats:title>\n<jats:p>People who developed pre-diabetes (<jats:italic>n<\/jats:italic>\u2009=\u2009555) and\/or T2D (<jats:italic>n<\/jats:italic>\u2009=\u200973) were older, had higher BMI, blood pressure, glucose, LDL cholesterol, and lower eGFR. After multivariable selection, PAPP-A (pappalysin-1) was the only circulating protein associated with the onset of both pre-diabetes and T2D with associations persisting at visit 4 (i.e. \u224820 years later). FGF-21 (fibroblast growth factor 21) was a strong prognosticator for incident T2D in the longitudinal analysis, but not in the cross-sectional analysis. The heritability of the circulating PAPP-A was estimated at 44%. In GWAS analysis, the SNP rs634737 was associated with PAPP-A both at V1 and V4. External replication also showed lower levels of PAPP-A in patients with T2D.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title><jats:italic>Conclusions:<\/jats:italic><\/jats:title>\n<jats:p>The risk of developing pre-diabetes and T2D increases with age and with features of the metabolic syndrome. Circulating PAPP-A, which has an important genetic component, was associated with both the development and presence of pre-diabetes and T2D.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-20-0246","type":"journal-article","created":{"date-parts":[[2020,6,19]],"date-time":"2020-06-19T16:08:17Z","timestamp":1592582897000},"page":"285-295","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":13,"title":["Circulating plasma proteins and new-onset diabetes in a population-based study: proteomic and genomic insights from the STANISLAS cohort"],"prefix":"10.1093","volume":"183","author":[{"given":"Jo\u00e3o Pedro","family":"Ferreira","sequence":"first","affiliation":[{"name":"1Universit\u00e9 de Lorraine, INSERM, Centre d\u2019Investigations Cliniques Plurith\u00e9matique 1433, INSERM 1116, CHRU de Nancy, FCRIN INI-CRCT, Nancy, France"}]},{"given":"Zohra","family":"Lamiral","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Lorraine, INSERM, Centre d\u2019Investigations Cliniques Plurith\u00e9matique 1433, INSERM 1116, CHRU de Nancy, FCRIN INI-CRCT, Nancy, France"}]},{"given":"Constance","family":"Xhaard","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Lorraine, INSERM, Centre d\u2019Investigations Cliniques Plurith\u00e9matique 1433, INSERM 1116, CHRU de Nancy, FCRIN INI-CRCT, Nancy, France"}]},{"given":"K\u00e9vin","family":"Duarte","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Lorraine, INSERM, Centre d\u2019Investigations Cliniques Plurith\u00e9matique 1433, INSERM 1116, CHRU de Nancy, FCRIN INI-CRCT, Nancy, France"}]},{"given":"Emmanuel","family":"Bresso","sequence":"additional","affiliation":[{"name":"2Universit\u00e9 de Lorraine, CNRS, Inria, LORIA, Nancy, France"}]},{"given":"Marie-Dominique","family":"Devignes","sequence":"additional","affiliation":[{"name":"2Universit\u00e9 de Lorraine, CNRS, Inria, LORIA, Nancy, France"}]},{"given":"Edith","family":"Le Floch","sequence":"additional","affiliation":[{"name":"3Universit\u00e9 Paris-Saclay, CEA, Centre National de Recherche en G\u00e9nomique Humaine, Evry, France"}]},{"given":"Claire Dandine","family":"Roulland","sequence":"additional","affiliation":[{"name":"3Universit\u00e9 Paris-Saclay, CEA, Centre National de Recherche en G\u00e9nomique Humaine, Evry, France"}]},{"given":"Jean-Fran\u00e7ois","family":"Deleuze","sequence":"additional","affiliation":[{"name":"3Universit\u00e9 Paris-Saclay, CEA, Centre National de Recherche en G\u00e9nomique Humaine, Evry, France"}]},{"given":"Sandra","family":"Wagner","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Lorraine, INSERM, Centre d\u2019Investigations Cliniques Plurith\u00e9matique 1433, INSERM 1116, CHRU de Nancy, FCRIN INI-CRCT, Nancy, France"}]},{"given":"Bruno","family":"Guerci","sequence":"additional","affiliation":[{"name":"4Department of Endocrinology, CHRU de Nancy, Nancy, France"}]},{"given":"Nicolas","family":"Girerd","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Lorraine, INSERM, Centre d\u2019Investigations Cliniques Plurith\u00e9matique 1433, INSERM 1116, CHRU de Nancy, FCRIN INI-CRCT, Nancy, France"}]},{"given":"Faiez","family":"Zannad","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Lorraine, INSERM, Centre d\u2019Investigations Cliniques Plurith\u00e9matique 1433, INSERM 1116, CHRU de Nancy, FCRIN INI-CRCT, Nancy, France"}]},{"given":"Jean-Marc","family":"Boivin","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Lorraine, INSERM, Centre d\u2019Investigations Cliniques Plurith\u00e9matique 1433, INSERM 1116, CHRU de Nancy, FCRIN INI-CRCT, Nancy, France"}]},{"given":"Patrick","family":"Rossignol","sequence":"additional","affiliation":[{"name":"1Universit\u00e9 de Lorraine, INSERM, Centre d\u2019Investigations Cliniques Plurith\u00e9matique 1433, INSERM 1116, CHRU de Nancy, FCRIN INI-CRCT, Nancy, France"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/183\/3\/EJE-20-0246.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/183\/3\/EJE-20-0246.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:14:46Z","timestamp":1676391286000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/183\/3\/285\/6653689"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9]]},"references-count":0,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1530\/eje-20-0246","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9]]}}}