{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T11:09:45Z","timestamp":1793272185473,"version":"4.5.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"8","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,8,2]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              The mechanisms and relevance of impaired glucose homeostasis in advanced heart failure (\n              <jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content>\n              ) are poorly understood. The study goals were to examine glucose regulation, pancreatic endocrine function, and metabolic factors related to prognosis in patients with nondiabetic advanced HF.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              In total, 140 advanced\n              <jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content>\n              patients without known diabetes mellitus and 21 sex\u2010, age\u2010, and body mass index\u2013matched controls underwent body composition assessment, oral glucose tolerance testing, and measurement of glucose\u2010regulating hormones to model pancreatic \u03b2\u2010cell secretory response. Compared with controls,\n              <jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content>\n              patients had similar fasting glucose and insulin levels but higher levels after oral glucose tolerance testing. Insulin secretion was not impaired, but with increasing\n              <jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content>\n              severity, there was a reduction in glucose, insulin, and insulin\/glucagon ratio\u2014a signature of starvation. The insulin\/C\u2010peptide ratio was decreased in\n              <jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content>\n              , indicating enhanced insulin clearance, and this was correlated with lower cardiac output, hepatic insufficiency, right ventricular dysfunction, and body wasting. After a median of 449\u00a0days, 41% of patients experienced an adverse event (death, urgent transplant, or assist device). Increased glucagon and, paradoxically, low fasting plasma glucose displayed the strongest relations to outcome (\n              <jats:italic>P<\/jats:italic>\n              =0.01). Patients in the lowest quartile of fasting plasma glucose (3.8\u20135.1\u00a0mmol\u00b7L\n              <jats:sup>\u22121<\/jats:sup>\n              , 68\u2013101\u00a0mg\u00b7dL\n              <jats:sup>\u22121<\/jats:sup>\n              ) had 3\u2010times higher event risk than in the top quartile (6.0\u20137.9\u00a0mmol\u00b7L\n              <jats:sup>\u22121<\/jats:sup>\n              , 108\u2013142\u00a0mg\u00b7dL\n              <jats:sup>\u22121<\/jats:sup>\n              ; relative risk: 3.05 [95% confidence interval, 1.46\u20136.77];\n              <jats:italic>P<\/jats:italic>\n              =0.002).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Low fasting plasma glucose and increased glucagon are robust metabolic predictors of adverse events in advanced\n              <jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content>\n              . Pancreatic insulin secretion is preserved in advanced\n              <jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content>\n              , but levels decrease with increasing\n              <jats:styled-content style=\"fixed-case\">HF<\/jats:styled-content>\n              severity due to enhanced insulin clearance that is coupled with right heart failure and cardiac cachexia.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.116.005290","type":"journal-article","created":{"date-parts":[[2017,8,8]],"date-time":"2017-08-08T00:20:15Z","timestamp":1502151615000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":19,"title":["Glucose Homeostasis, Pancreatic Endocrine Function, and Outcomes in Advanced Heart Failure"],"prefix":"10.1161","volume":"6","author":[{"given":"Vojtech","family":"Melenovsky","sequence":"first","affiliation":[{"name":"Institute for Clinical and Experimental Medicine \u2013 IKEM, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Benes","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Medicine \u2013 IKEM, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janka","family":"Franekova","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Medicine \u2013 IKEM, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Kovar","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Medicine \u2013 IKEM, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barry A.","family":"Borlaug","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Disease, Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marketa","family":"Segetova","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Medicine \u2013 IKEM, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Tura","sequence":"additional","affiliation":[{"name":"CNR Institute of Neuroscience, Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tereza","family":"Pelikanova","sequence":"additional","affiliation":[{"name":"Institute for Clinical and Experimental Medicine \u2013 IKEM, Prague, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000450"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.294.3.334"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(74)90089-7"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.03.037"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/0026-0495(91)90075-8"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2005.02.093"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(97)00185-X"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.10260"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2016.03.008"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrendo.2013.234"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2011.05.042"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2013.06.046"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.96.2.526"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1530\/eje.0.1450727"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)07015-8"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2011.08.001"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00093.2002"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.2174\/1573399810666140214093600"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00280883"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchf.2015.05.012"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2008.08.081"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1042\/cs0860317"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurjhf\/hfs080"},{"key":"e_1_3_4_25_2","first-page":"608","article-title":"Insulin degradation: progress and potential","volume":"19","author":"Duckworth WC","year":"1998","unstructured":"Duckworth WC, Bennett RG, Hamel FG. 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