Valeria Grancini1, Maddalena Trombetta2, Maria Elena Lunati1, Dario Zimbalatti1, Maria Linda Boselli2, Stefano Gatti3, Maria Francesca Donato4, Veronica Resi1, Roberta D'Ambrosio4, Alessio Aghemo4, Giuseppe Pugliese5, Riccardo C Bonadonna6, Emanuela Orsi7. 1. Endocrinology and Metabolic Diseases Unit, Diabetes Service, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy. 2. Division of Endocrinology and Metabolic Diseases, University of Verona, Verona, Italy. 3. General Surgery Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy. 4. A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy. 5. Department of Clinical and Molecular Medicine, "La Sapienza" University, and Diabetes Unit, Sant'Andrea Hospital, Rome, Italy. 6. Department of Clinical and Experimental Medicine, University of Parma, and Division of Endocrinology, Azienda Ospedaliera Universitaria, Parma, Italy. 7. Endocrinology and Metabolic Diseases Unit, Diabetes Service, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy. Electronic address: e.orsi@policlinico.mi.it.
Abstract
BACKGROUND & AIMS: This study evaluated the contribution of β-cell dysfunction and insulin resistance to cirrhosis-associated diabetes. METHODS: One-hundred and sixty cirrhotic patients with normal fasting plasma glucose (FPG), three with impaired fasting glucose and seven with untreated diabetes mellitus (DM) underwent an extended oral glucose tolerance test (OGTT). The OGTT data were analyzed with a Minimal Model to estimate dynamic (derivative) control (DC) and static (proportional) control (PC) of β-cell function, and with the Oral Glucose Insulin Sensitivity (OGIS)-2h index to estimate insulin sensitivity. RESULTS: Twenty-six patients (15.6%) had normal glucose tolerance (NGT), 60 (35.8%) had impaired glucose tolerance (IGT), and 84 (48.6%) had DM. DC was significantly reduced in DM vs. NGT and IGT patients. PC was significantly impaired in DM and IGT vs. NGT patients and in DM vs. IGT subjects. The OGIS-2h index was significantly reduced to a similar extent in DM and IGT vs. NGT patients. Patients with Child-Pugh class B and C cirrhosis had reduced DC and PC, but not OGIS-2h values, as compared with subjects in class A. Moreover, Child-Pugh class/score was an independent predictor of β-cell function even after adjustment for glucose tolerance. CONCLUSIONS: Abnormalities of glucose tolerance occur frequently in cirrhosis even in patients with normal FPG, thereby supporting the importance of performing an OGTT. Transition from IGT to DM is driven primarily by β-cell dysfunction. Insulin secretion worsens in parallel with the severity of liver disease, thus suggesting a detrimental effect of liver failure on pancreatic islets on its own.
BACKGROUND & AIMS: This study evaluated the contribution of β-cell dysfunction and insulin resistance to cirrhosis-associated diabetes. METHODS: One-hundred and sixty cirrhotic patients with normal fasting plasma glucose (FPG), three with impaired fasting glucose and seven with untreated diabetes mellitus (DM) underwent an extended oral glucose tolerance test (OGTT). The OGTT data were analyzed with a Minimal Model to estimate dynamic (derivative) control (DC) and static (proportional) control (PC) of β-cell function, and with the Oral Glucose Insulin Sensitivity (OGIS)-2h index to estimate insulin sensitivity. RESULTS: Twenty-six patients (15.6%) had normal glucose tolerance (NGT), 60 (35.8%) had impaired glucose tolerance (IGT), and 84 (48.6%) had DM. DC was significantly reduced in DM vs. NGT and IGT patients. PC was significantly impaired in DM and IGT vs. NGT patients and in DM vs. IGT subjects. The OGIS-2h index was significantly reduced to a similar extent in DM and IGT vs. NGT patients. Patients with Child-Pugh class B and C cirrhosis had reduced DC and PC, but not OGIS-2h values, as compared with subjects in class A. Moreover, Child-Pugh class/score was an independent predictor of β-cell function even after adjustment for glucose tolerance. CONCLUSIONS:Abnormalities of glucose tolerance occur frequently in cirrhosis even in patients with normal FPG, thereby supporting the importance of performing an OGTT. Transition from IGT to DM is driven primarily by β-cell dysfunction. Insulin secretion worsens in parallel with the severity of liver disease, thus suggesting a detrimental effect of liver failure on pancreatic islets on its own.
Authors: Diego García-Compeán; José Alberto González-González; Fernando Javier Lavalle-González; Emmanuel Irineo González-Moreno; Jesús Zacarías Villarreal-Pérez; Héctor Jesús Maldonado-Garza Journal: World J Gastroenterol Date: 2016-03-14 Impact factor: 5.742
Authors: Miguel Jiménez-Pérez; Rocío González-Grande; Edith Omonte Guzmán; Víctor Amo Trillo; Juan Miguel Rodrigo López Journal: World J Gastroenterol Date: 2016-07-28 Impact factor: 5.742