Prospective Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2015; 21(15): 4688-4695
Published online Apr 21, 2015. doi: 10.3748/wjg.v21.i15.4688
Pancreatic fat and β-cell function in overweight/obese children with nonalcoholic fatty liver disease
Lucia Pacifico, Michele Di Martino, Caterina Anania, Gian Marco Andreoli, Mario Bezzi, Carlo Catalano, Claudio Chiesa
Lucia Pacifico, Caterina Anania, Gian Marco Andreoli, Department of Pediatrics and Child Neuropsychiatry, Sapienza University of Rome, 00161 Rome, Italy
Michele Di Martino, Mario Bezzi, Carlo Catalano, Department of Radiological Sciences, Sapienza University of Rome, 00161 Rome, Italy
Claudio Chiesa, Institute of Translational Pharmacology, National Research Council, 00133 Rome, Italy
Author contributions: Pacifico L, Anania C and Chiesa C designed the study, analyzed the data and wrote the manuscript; Di Martino M and Andreoli GM collected the data; Di Martino M, Andreoli GM, Bezzi M and Catalano C performed the measurements and analyses; all the authors participated in the critical review and in the final approval of the manuscript.
Supported by Sapienza University of Rome (Progetti di Ricerca Universitaria 2011-2012).
Ethics approval: The study protocol was reviewed and approved by the Ethics Committee of Policlinico Umberto I Hospital, Rome, Italy.
Clinical trial registration: Prot. 432/12; Rif. 2464/24.05.2012.
Informed consent: Written informed consent was obtained from the next of kin, caretakers, or guardians on behalf of the children enrolled in this study, in accordance with principles of the Helsinki Declaration.
Conflict-of-interest: There are no potential conflicts of interest relevant to this article.
Data sharing: Data are available from the corresponding author at the provided e-mail address.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Claudio Chiesa, MD, Institute of Translational Pharmacology, National Research Council, Via Fosso del Cavaliere 100, 00133 Rome, Italy. claudio.chiesa@ift.cnr.it
Telephone: +39-6-49979215 Fax: +39-6-49979216
Received: November 26, 2014
Peer-review started: November 27, 2014
First decision: December 11, 2014
Revised: December 19, 2014
Accepted: January 16, 2015
Article in press: January 16, 2015
Published online: April 21, 2015
Processing time: 144 Days and 19 Hours
Abstract

AIM: To analyze the associations of pancreatic fat with other fat depots and β-cell function in pediatric nonalcoholic fatty liver disease (NAFLD).

METHODS: We examined 158 overweight/obese children and adolescents, 80 with NAFLD [hepatic fat fraction (HFF) ≥ 5%] and 78 without fatty liver. Visceral adipose tissue (VAT), pancreatic fat fraction (PFF) and HFF were determined by magnetic resonance imaging. Estimates of insulin sensitivity were calculated using the homeostasis model assessment of insulin resistance (HOMA-IR), defined by fasting insulin and fasting glucose and whole-body insulin sensitivity index (WBISI), based on mean values of insulin and glucose obtained from oral glucose tolerance test and the corresponding fasting values. Patients were considered to have prediabetes if they had either: (1) impaired fasting glucose, defined as a fasting glucose level ≥ 100 mg/dL to < 126 mg/dL; (2) impaired glucose tolerance, defined as a 2 h glucose concentration between ≥ 140 mg/dL and < 200 mg/dL; or (3) hemoglobin A1c value of ≥ 5.7% to < 6.5%.

RESULTS: PFF was significantly higher in NAFLD patients compared with subjects without liver involvement. PFF was significantly associated with HFF and VAT, as well as fasting insulin, C peptide, HOMA-IR, and WBISI. The association between PFF and HFF was no longer significant after adjusting for age, gender, Tanner stage, body mass index (BMI)-SD score, and VAT. In multiple regression analysis with WBISI or HOMA-IR as the dependent variables, against the covariates age, gender, Tanner stage, BMI-SD score, VAT, PFF, and HFF, the only variable significantly associated with WBISI (standardized coefficient B, -0.398; P = 0.001) as well as HOMA-IR (0.353; P = 0.003) was HFF. Children with prediabetes had higher PFF and HFF than those without. PFF and HFF were significantly associated with prediabetes after adjustment for clinical variables. When all fat depots where included in the same model, only HFF remained significantly associated with prediabetes (OR = 3.38; 95%CI: 1.10-10.4; P = 0.034).

CONCLUSION: In overweight/obese children with NAFLD, pancreatic fat is increased compared with those without liver involvement. However, only liver fat is independently related to prediabetes.

Keywords: Nonalcoholic fatty liver disease; Pancreatic fat; Visceral fat; Beta-cell function; Children

Core tip: Recent studies in children demonstrated that the prevalence of prediabetes increases with increasing hepatic fat content, and that fatty liver plays a central role in the impairment of liver, muscle and adipose insulin sensitivity. Pancreatic fat was identified as a novel obesity-related fat depot, which might contribute to the development of β-cell dysfunction. This study demonstrated that in overweight/obese children with nonalcoholic fatty liver disease (NAFLD), pancreatic fat is increased compared with those without NAFLD. However, only liver fat is independently related to prediabetes. Early intervention during childhood to recognize NAFLD might be critical in averting an unfavorable metabolic phenotype.