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Central role of the β-cell in driving regression of diabetes after liver transplantation in cirrhotic patients.

Abstract：

BACKGROUND & AIMS:Diabetes occurring as a direct consequence of loss of liver function is usually characterized by non-diabetic fasting plasma glucose (FPG) and haemoglobin A1c (HbA1c) levels and should regress after orthotopic liver transplantation (OLT). This observational, longitudinal study investigated the relationship between the time-courses of changes in all 3 direct determinants of glucose regulation, i.e., β-cell function, insulin clearance and insulin sensitivity, and diabetes regression after OLT. METHODS:Eighty cirrhotic patients with non-diabetic FPG and HbA1c levels underwent an extended oral glucose tolerance test (OGTT) before and 3, 6, 12 and 24 months after OLT. The OGTT data were analysed with a mathematical model to estimate derivative control (DC) and proportional control (PC) of β-cell function and insulin clearance (which determine insulin bioavailability), and with the Oral Glucose Insulin Sensitivity (OGIS)-2 h index to estimate insulin sensitivity. RESULTS:At baseline, 36 patients were diabetic (45%) and 44 were non-diabetic (55%). Over the 2-year follow-up, 23 diabetic patients (63.9%) regressed to non-diabetic glucose regulation, whereas 13 did not (36.1%); moreover, 4 non-diabetic individuals progressed to diabetes (9.1%), whereas 40 did not (90.9%). Both DC and PC increased in regressors (from month 3 and 24, respectively) and decreased in progressors, whereas they remained stable in non-regressors and only PC decreased in non-progressors. Insulin clearance increased in all groups, apart from progressors. Likewise, OGIS-2 h improved at month 3 in all groups, but thereafter it continued to improve only in regressors, whereas it returned to baseline values in the other groups. CONCLUSIONS:Increased insulin bioavailability driven by improved β-cell function plays a central role in favouring diabetes regression after OLT, in the presence of a sustained improvement of insulin sensitivity. LAY SUMMARY:Diabetes occurring in cirrhosis as a direct consequence of loss of liver function should regress after transplantation of a new functioning liver, though the pathophysiological mechanisms are unclear. This is the first study evaluating the contribution of all 3 direct determinants of insulin-dependent glucose regulation using a sophisticated mathematical model. Results show that β-cell function is the key process governing favourable or detrimental changes in glucose regulation in cirrhotic patients undergoing transplantation, pointing to the need to develop therapies to sustain β-cell function in these individuals. TRIAL REGISTRATION:ClinicalTrials.gov, NCT02038517.

journal_name

J Hepatol

journal_title

Journal of hepatology

authors

Grancini V,Trombetta M,Lunati ME,Boselli ML,Gatti S,Donato MF,Palmieri E,Resi V,Pugliese G,Bonadonna RC,Orsi E

doi

10.1016/j.jhep.2019.01.015

subject

Has Abstract

pub_date

2019-05-01 00:00:00

pages

954-962

issue

eissn

0168-8278

issn

1600-0641

pii

S0168-8278(19)30028-5

journal_volume

pub_type

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Central role of the β-cell in driving regression of diabetes after liver transplantation in cirrhotic patients.