title: Contribution of β-cell dysfunction and insulin resistance to cirrhosis-associated diabetes: Role of severity of liver disease.
abstract: OBJECTIVE
  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: Endocrinology and Metabolic Diseases Unit, Diabetes Service, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy.
authors: Valeria
authors: V
authors: Grancini
authors: Division of Endocrinology and Metabolic Diseases, University of Verona, Verona, Italy.
authors: Maddalena
authors: M
authors: Trombetta
authors: Endocrinology and Metabolic Diseases Unit, Diabetes Service, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy.
authors: Maria Elena
authors: ME
authors: Lunati
authors: Endocrinology and Metabolic Diseases Unit, Diabetes Service, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy.
authors: Dario
authors: D
authors: Zimbalatti
authors: Division of Endocrinology and Metabolic Diseases, University of Verona, Verona, Italy.
authors: Maria Linda
authors: ML
authors: Boselli
authors: General Surgery Unit, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy.
authors: Stefano
authors: S
authors: Gatti
authors: A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy.
authors: Maria Francesca
authors: MF
authors: Donato
authors: Endocrinology and Metabolic Diseases Unit, Diabetes Service, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy.
authors: Veronica
authors: V
authors: Resi
authors: A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy.
authors: Roberta
authors: R
authors: D'Ambrosio
authors: A. Migliavacca Center for Liver Disease, Division of Gastroenterology and Hepatology, IRCCS "Cà Granda - Ospedale Maggiore Policlinico" Foundation, University of Milan, Milan, Italy.
authors: Alessio
authors: A
authors: Aghemo
authors: Department of Clinical and Molecular Medicine, "La Sapienza" University, and Diabetes Unit, Sant'Andrea Hospital, Rome, Italy.
authors: Giuseppe
authors: G
authors: Pugliese
authors: Department of Clinical and Experimental Medicine, University of Parma, and Division of Endocrinology, Azienda Ospedaliera Universitaria, Parma, Italy.
authors: Riccardo C
authors: RC
authors: Bonadonna
authors: 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.
authors: Emanuela
authors: E
authors: Orsi
mesh_terms: D001786:Blood Glucose / Q000378:metabolism; D003430:Cross-Sectional Studies; D048909:Diabetes Complications / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D005951:Glucose Tolerance Test; D019698:Hepatitis C, Chronic / Q000150:complications; D006801:Humans; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000502:physiology*; D008103:Liver Cirrhosis / Q000150:complications* / Q000209:etiology / Q000503:physiopathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index
chemical_list: D001786:Blood Glucose
keywords: Child-Pugh classification; Diabetes mellitus; Insulin resistance; Liver cirrhosis; β-Cell dysfunction