Prevalence of prediabetes and diabetes in children and adolescents with biopsy-proven nonalcoholic fatty liver disease

Valerio Nobili, Alessandro Mantovani, Stefano Cianfarani, Anna Alisi, Antonella Mosca, Maria Rita Sartorelli, Claudio Maffeis, Rohit Loomba, Christopher D Byrne, Giovanni Targher

Research output: Contribution to journalArticle

Abstract

BACKGROUND & AIMS: We undertook a cross-sectional study of children/adolescents with and without non-alcoholic fatty liver disease (NAFLD) to compare the prevalence of prediabetes and diabetes, and to examine the role of abnormal glucose tolerance as a predictor of liver disease severity.

METHODS: We recruited a cohort of 599 Caucasian children/adolescents with biopsy-proven NAFLD, and 118 children/adolescents without NAFLD, who were selected to be similar for age, sex, body mass index and waist circumference to those with NAFLD. The diagnosis of prediabetes and diabetes was based on either hemoglobin A1c, fasting plasma glucose or 2-hour post-load glucose concentrations.

RESULTS: Children/adolescents with NAFLD had a significantly higher prevalence of abnormal glucose tolerance (prediabetes or diabetes) than those without NAFLD (20.6% vs. 11%, p=0.02). In particular, 124 (20.6%) of children/adolescents with NAFLD had abnormal glucose tolerance, with 19.8% (n=119) satisfying the diagnostic criteria for prediabetes and 0.8% (n=5) satisfying the criteria for diabetes. The combined presence of prediabetes and diabetes was associated with a two-fold increased risk of non-alcoholic steatohepatitis (NASH; unadjusted-OR 2.19, 95%CI 1.47-3.29, p<0.001). However, this association was attenuated (but remained significant) after adjustment for age, sex, waist circumference (adjusted-OR 1.69, 95%CI 1.06-2.69, p=0.032), and also the patatin-like phospholipase domain-containing protein-3 rs738409 polymorphism. These two latter variables were strongly associated with NASH.

CONCLUSIONS: Abnormal glucose tolerance (especially prediabetes) is highly prevalent among children/adolescents with biopsy-proven NAFLD. These children also have a higher risk of NASH, though central adiposity is the factor that is most strongly associated with NASH.

LAY SUMMARY: Children with biopsy-proven NAFLD have a higher prevalence of abnormal glucose tolerance (prediabetes or type 2 diabetes) than children without NAFLD. Children with biopsy-proven NAFLD and abnormal glucose tolerance also have a higher prevalence of NASH compared with those with normal glucose tolerance, though central adiposity is the factor that is most strongly associated with NASH.

Original languageEnglish
JournalJournal of Hepatology
DOIs
Publication statusE-pub ahead of print - Jul 4 2019

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Prediabetic State
Biopsy
Glucose
Adiposity
Waist Circumference
Non-alcoholic Fatty Liver Disease
Central Tolerance
Phospholipases
Fatty Liver
Type 2 Diabetes Mellitus
Liver Diseases
Fasting
Hemoglobins
Body Mass Index
Cross-Sectional Studies

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Prevalence of prediabetes and diabetes in children and adolescents with biopsy-proven nonalcoholic fatty liver disease. / Nobili, Valerio; Mantovani, Alessandro; Cianfarani, Stefano; Alisi, Anna; Mosca, Antonella; Rita Sartorelli, Maria; Maffeis, Claudio; Loomba, Rohit; Byrne, Christopher D; Targher, Giovanni.

In: Journal of Hepatology, 04.07.2019.

Research output: Contribution to journalArticle

Nobili, Valerio ; Mantovani, Alessandro ; Cianfarani, Stefano ; Alisi, Anna ; Mosca, Antonella ; Rita Sartorelli, Maria ; Maffeis, Claudio ; Loomba, Rohit ; Byrne, Christopher D ; Targher, Giovanni. / Prevalence of prediabetes and diabetes in children and adolescents with biopsy-proven nonalcoholic fatty liver disease. In: Journal of Hepatology. 2019.
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title = "Prevalence of prediabetes and diabetes in children and adolescents with biopsy-proven nonalcoholic fatty liver disease",
abstract = "BACKGROUND & AIMS: We undertook a cross-sectional study of children/adolescents with and without non-alcoholic fatty liver disease (NAFLD) to compare the prevalence of prediabetes and diabetes, and to examine the role of abnormal glucose tolerance as a predictor of liver disease severity.METHODS: We recruited a cohort of 599 Caucasian children/adolescents with biopsy-proven NAFLD, and 118 children/adolescents without NAFLD, who were selected to be similar for age, sex, body mass index and waist circumference to those with NAFLD. The diagnosis of prediabetes and diabetes was based on either hemoglobin A1c, fasting plasma glucose or 2-hour post-load glucose concentrations.RESULTS: Children/adolescents with NAFLD had a significantly higher prevalence of abnormal glucose tolerance (prediabetes or diabetes) than those without NAFLD (20.6{\%} vs. 11{\%}, p=0.02). In particular, 124 (20.6{\%}) of children/adolescents with NAFLD had abnormal glucose tolerance, with 19.8{\%} (n=119) satisfying the diagnostic criteria for prediabetes and 0.8{\%} (n=5) satisfying the criteria for diabetes. The combined presence of prediabetes and diabetes was associated with a two-fold increased risk of non-alcoholic steatohepatitis (NASH; unadjusted-OR 2.19, 95{\%}CI 1.47-3.29, p<0.001). However, this association was attenuated (but remained significant) after adjustment for age, sex, waist circumference (adjusted-OR 1.69, 95{\%}CI 1.06-2.69, p=0.032), and also the patatin-like phospholipase domain-containing protein-3 rs738409 polymorphism. These two latter variables were strongly associated with NASH.CONCLUSIONS: Abnormal glucose tolerance (especially prediabetes) is highly prevalent among children/adolescents with biopsy-proven NAFLD. These children also have a higher risk of NASH, though central adiposity is the factor that is most strongly associated with NASH.LAY SUMMARY: Children with biopsy-proven NAFLD have a higher prevalence of abnormal glucose tolerance (prediabetes or type 2 diabetes) than children without NAFLD. Children with biopsy-proven NAFLD and abnormal glucose tolerance also have a higher prevalence of NASH compared with those with normal glucose tolerance, though central adiposity is the factor that is most strongly associated with NASH.",
author = "Valerio Nobili and Alessandro Mantovani and Stefano Cianfarani and Anna Alisi and Antonella Mosca and {Rita Sartorelli}, Maria and Claudio Maffeis and Rohit Loomba and Byrne, {Christopher D} and Giovanni Targher",
note = "Copyright {\circledC} 2019. Published by Elsevier B.V.",
year = "2019",
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doi = "10.1016/j.jhep.2019.06.023",
language = "English",
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TY - JOUR

T1 - Prevalence of prediabetes and diabetes in children and adolescents with biopsy-proven nonalcoholic fatty liver disease

AU - Nobili, Valerio

AU - Mantovani, Alessandro

AU - Cianfarani, Stefano

AU - Alisi, Anna

AU - Mosca, Antonella

AU - Rita Sartorelli, Maria

AU - Maffeis, Claudio

AU - Loomba, Rohit

AU - Byrne, Christopher D

AU - Targher, Giovanni

N1 - Copyright © 2019. Published by Elsevier B.V.

PY - 2019/7/4

Y1 - 2019/7/4

N2 - BACKGROUND & AIMS: We undertook a cross-sectional study of children/adolescents with and without non-alcoholic fatty liver disease (NAFLD) to compare the prevalence of prediabetes and diabetes, and to examine the role of abnormal glucose tolerance as a predictor of liver disease severity.METHODS: We recruited a cohort of 599 Caucasian children/adolescents with biopsy-proven NAFLD, and 118 children/adolescents without NAFLD, who were selected to be similar for age, sex, body mass index and waist circumference to those with NAFLD. The diagnosis of prediabetes and diabetes was based on either hemoglobin A1c, fasting plasma glucose or 2-hour post-load glucose concentrations.RESULTS: Children/adolescents with NAFLD had a significantly higher prevalence of abnormal glucose tolerance (prediabetes or diabetes) than those without NAFLD (20.6% vs. 11%, p=0.02). In particular, 124 (20.6%) of children/adolescents with NAFLD had abnormal glucose tolerance, with 19.8% (n=119) satisfying the diagnostic criteria for prediabetes and 0.8% (n=5) satisfying the criteria for diabetes. The combined presence of prediabetes and diabetes was associated with a two-fold increased risk of non-alcoholic steatohepatitis (NASH; unadjusted-OR 2.19, 95%CI 1.47-3.29, p<0.001). However, this association was attenuated (but remained significant) after adjustment for age, sex, waist circumference (adjusted-OR 1.69, 95%CI 1.06-2.69, p=0.032), and also the patatin-like phospholipase domain-containing protein-3 rs738409 polymorphism. These two latter variables were strongly associated with NASH.CONCLUSIONS: Abnormal glucose tolerance (especially prediabetes) is highly prevalent among children/adolescents with biopsy-proven NAFLD. These children also have a higher risk of NASH, though central adiposity is the factor that is most strongly associated with NASH.LAY SUMMARY: Children with biopsy-proven NAFLD have a higher prevalence of abnormal glucose tolerance (prediabetes or type 2 diabetes) than children without NAFLD. Children with biopsy-proven NAFLD and abnormal glucose tolerance also have a higher prevalence of NASH compared with those with normal glucose tolerance, though central adiposity is the factor that is most strongly associated with NASH.

AB - BACKGROUND & AIMS: We undertook a cross-sectional study of children/adolescents with and without non-alcoholic fatty liver disease (NAFLD) to compare the prevalence of prediabetes and diabetes, and to examine the role of abnormal glucose tolerance as a predictor of liver disease severity.METHODS: We recruited a cohort of 599 Caucasian children/adolescents with biopsy-proven NAFLD, and 118 children/adolescents without NAFLD, who were selected to be similar for age, sex, body mass index and waist circumference to those with NAFLD. The diagnosis of prediabetes and diabetes was based on either hemoglobin A1c, fasting plasma glucose or 2-hour post-load glucose concentrations.RESULTS: Children/adolescents with NAFLD had a significantly higher prevalence of abnormal glucose tolerance (prediabetes or diabetes) than those without NAFLD (20.6% vs. 11%, p=0.02). In particular, 124 (20.6%) of children/adolescents with NAFLD had abnormal glucose tolerance, with 19.8% (n=119) satisfying the diagnostic criteria for prediabetes and 0.8% (n=5) satisfying the criteria for diabetes. The combined presence of prediabetes and diabetes was associated with a two-fold increased risk of non-alcoholic steatohepatitis (NASH; unadjusted-OR 2.19, 95%CI 1.47-3.29, p<0.001). However, this association was attenuated (but remained significant) after adjustment for age, sex, waist circumference (adjusted-OR 1.69, 95%CI 1.06-2.69, p=0.032), and also the patatin-like phospholipase domain-containing protein-3 rs738409 polymorphism. These two latter variables were strongly associated with NASH.CONCLUSIONS: Abnormal glucose tolerance (especially prediabetes) is highly prevalent among children/adolescents with biopsy-proven NAFLD. These children also have a higher risk of NASH, though central adiposity is the factor that is most strongly associated with NASH.LAY SUMMARY: Children with biopsy-proven NAFLD have a higher prevalence of abnormal glucose tolerance (prediabetes or type 2 diabetes) than children without NAFLD. Children with biopsy-proven NAFLD and abnormal glucose tolerance also have a higher prevalence of NASH compared with those with normal glucose tolerance, though central adiposity is the factor that is most strongly associated with NASH.

U2 - 10.1016/j.jhep.2019.06.023

DO - 10.1016/j.jhep.2019.06.023

M3 - Article

JO - Journal of Hepatology

JF - Journal of Hepatology

SN - 0168-8278

ER -