Contribution of β-cell dysfunction and insulin resistance to cirrhosis-associated diabetes: Role of severity of liver disease

Valeria Grancini, Maddalena Trombetta, Maria Elena Lunati, Dario Zimbalatti, Maria Linda Boselli, Stefano Gatti, Maria Francesca Donato, Veronica Resi, Roberta D'Ambrosio, Alessio Aghemo, Giuseppe Pugliese, Riccardo C. Bonadonna, Emanuela Orsi

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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)-2 h 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-2 h 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-2 h 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.

Original languageEnglish
Pages (from-to)1484-1490
Number of pages7
JournalJournal of Hepatology
Volume63
Issue number6
DOIs
Publication statusPublished - Dec 1 2015

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Keywords

  • Child-Pugh classification
  • Diabetes mellitus
  • Insulin resistance
  • Liver cirrhosis
  • β-Cell dysfunction

ASJC Scopus subject areas

  • Hepatology

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