{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T10:01:39Z","timestamp":1790330499923,"version":"4.1.0"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":5662,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"name":"Istituto Scientifico H San Raffaele","award":["PZ709"],"award-info":[{"award-number":["PZ709"]}]},{"name":"Istituto Scientifico H San Raffaele","award":["PZ806)"],"award-info":[{"award-number":["PZ806)"]}]},{"name":"Italian Minister of Health (G Perseghin)","award":["030.5\/RF96.305"],"award-info":[{"award-number":["030.5\/RF96.305"]}]},{"name":"Italian National Research Council","award":["CNR 97.00485.CT04"],"award-info":[{"award-number":["CNR 97.00485.CT04"]}]},{"name":"L Luzi is a recipient of a grant of the Associazione Italiana Ricerca Cancro (AIRC): \u201cProtein metabolism in patients with hepatocarcinoma before and after liver transplantation.\u201d"},{"name":"V Mazzaferro is a recipient of the grant of the Associazione Italiana Ricerca Cancro (AIRC): \u201cNew therapeutic strategies for hepatocellular carcinomas.\u201d"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2000,3]]},"abstract":"<jats:sec>\n            <jats:title\/>\n            <jats:p>Diabetes mellitus frequently complicates cirrhosis but the pathogenic mechanisms are unknown. To assess the contribution of reduced insulin action and secretion, 24 cirrhotic-diabetic patients waiting for liver transplant because of an unresectable hepatocarcinoma underwent an oral glucose tolerance test (OGTT) to assess the \u03b2-cell function and an insulin clamp combined with [3-<jats:sup>3<\/jats:sup>H]glucose infusion to measure whole body glucose metabolism before and 2 years after the transplant. Seven cirrhotic nondiabetic patients, 11 patients with chronic uveitis on similar immunosuppressive therapy, and 7 healthy subjects served as control groups. Cirrhotic patients showed a profound insulin resistance, and diabetics in addition also showed increased endogenous glucose production (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; .05) and insulin deficiency during the OGTT (<jats:italic toggle=\"yes\">P<\/jats:italic> &lt; .05). Liver transplantation normalized endogenous glucose production and insulin sensitivity but failed to cure diabetes in 8 of the 24 patients because a markedly low insulin response during the OGTT. Age, body mass index, family history of diabetes, immunosuppressive drugs, and pathogenesis of cirrhosis did not predict in whom liver transplant was going to cure diabetes. On the contrary, a reduced secretory response characterized the patients in whom the transplant would not be curative. In summary, insulin resistance was a primary event complicating cirrhosis but additional \u03b2-cell secretory defects were crucial for development of diabetes. Liver transplantation, lessening insulin resistance, cured hepatogenous diabetes in 67% of cirrhotic-diabetic patients; nevertheless 33% were still diabetics because the persistence of a reduced \u03b2-cell function, which makes these patients eventually eligible for combined islet transplantation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.510310320","type":"journal-article","created":{"date-parts":[[2004,7,28]],"date-time":"2004-07-28T07:51:16Z","timestamp":1091001076000},"page":"694-703","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":116,"title":["Contribution of reduced insulin sensitivity and secretion to the pathogenesis of hepatogenous diabetes: Effect of liver transplantation"],"prefix":"10.1097","volume":"31","author":[{"given":"Gianluca","family":"Perseghin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincenzo","family":"Mazzaferro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia Piceni","family":"Sereni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Regalia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Benedini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Bazzigaluppi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Pulvirenti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana Antonio Silva","family":"Le\u00e3o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giliola","family":"Calori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Romito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dario","family":"Baratti","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livio","family":"Luzi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"10.1002\/hep.510310320-BIB1|cit1","first-page":"38","volume-title":"Der Diabetes Mellitus","author":"Naunyn","year":"1898"},{"key":"10.1002\/hep.510310320-BIB2|cit2","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1016\/S0140-6736(67)90334-0","article-title":"Glucose tolerance and diabetes in chronic liver disease","volume":"2","author":"Megyesi","year":"1967","journal-title":"Lancet"},{"key":"10.1002\/hep.510310320-BIB3|cit3","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1007\/BF02233205","article-title":"Cirrhosis and diabetes. 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