TY - JOUR
T1 - Contribution of β-cell dysfunction and insulin resistance to cirrhosis-associated diabetes
T2 - Role of severity of liver disease
AU - Grancini, Valeria
AU - Trombetta, Maddalena
AU - Lunati, Maria Elena
AU - Zimbalatti, Dario
AU - Boselli, Maria Linda
AU - Gatti, Stefano
AU - Donato, Maria Francesca
AU - Resi, Veronica
AU - D'Ambrosio, Roberta
AU - Aghemo, Alessio
AU - Pugliese, Giuseppe
AU - Bonadonna, Riccardo C.
AU - Orsi, Emanuela
PY - 2015/12/1
Y1 - 2015/12/1
N2 - 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.
AB - 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.
KW - Child-Pugh classification
KW - Diabetes mellitus
KW - Insulin resistance
KW - Liver cirrhosis
KW - β-Cell dysfunction
UR - http://www.scopus.com/inward/record.url?scp=84951103456&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84951103456&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2015.08.011
DO - 10.1016/j.jhep.2015.08.011
M3 - Article
C2 - 26297917
AN - SCOPUS:84951103456
VL - 63
SP - 1484
EP - 1490
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 6
ER -