Highlights
- •The prevalence of abnormal glucose tolerance is uncertain in children with biopsy-proven NAFLD.
- •Children with NAFLD have a higher prevalence of abnormal glucose tolerance than those without NAFLD.
- •Children with NAFLD and abnormal glucose tolerance have a higher prevalence of NASH than those with normal glucose tolerance.
- •Central adiposity is the factor that is most strongly associated with NASH.
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 h 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%) 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 nearly 2.2-fold increased risk of non-alcoholic
steatohepatitis (NASH; unadjusted odds ratio 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 odds ratio 1.69, 95% CI 1.06–2.69, p = 0.032), and the PNPLA3 rs738409 polymorphism. Both this PNPLA3 polymorphism and waist circumference 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 non-alcoholic fatty liver disease (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 the progressive form of disease, non-alcoholic steatohepatitis,
than those with normal glucose tolerance, though central adiposity is the factor that
is most strongly associated with non-alcoholic steatohepatitis.
Graphical abstract
Graphical Abstract
Keywords
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of HepatologyAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- Current concepts in pediatric nonalcoholic fatty liver disease.Gastroenterol Clin North Am. 2017; 46: 217-231
- Nonalcoholic fatty liver disease in children.Semin Liver Dis. 2018; 38: 1-13
- Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention.Nat Rev Gastroenterol Hepatol. 2018; 15: 11-20
- Tests for diagnosing and monitoring non-alcoholic fatty liver disease in adults.BMJ. 2018; 362k2734
- Nonalcoholic fatty liver disease in children: hepatic and extrahepatic complications.Pediatr Clin North Am. 2017; 64: 659-675
- NAFLD: a multisystem disease.J Hepatol. 2015; 62: S47-S64
- Non-alcoholic fatty liver disease and its relationship with cardiovascular disease and other extra-hepatic diseases.Gut. 2017; 66: 1138-1153
- Nonalcoholic fatty liver disease and chronic vascular complications of diabetes mellitus.Nat Rev Endocrinol. 2018; 14: 99-114
- Obesity, insulin resistance, and other clinicopathological correlates of pediatric nonalcoholic fatty liver disease.J Pediatr. 2003; 143: 500-505
- Glucose dysregulation and hepatic steatosis in obese adolescents: is there a link?.Hepatology. 2009; 49: 1896-1903
- Association between metabolic syndrome and liver histology among children with nonalcoholic fatty liver disease.Am J Gastroenterol. 2010; 105: 2093-2102
- Nonalcoholic Steatohepatitis Clinical Research Network. Prevalence of prediabetes and type 2 diabetes in children with nonalcoholic fatty liver disease.JAMA Pediatr. 2016; 170e161971
- Diagnosis of nonalcoholic fatty liver disease in children and adolescents: position paper of the ESPGHAN Hepatology Committee.J Pediatr Gastroenterol Nutr. 2012; 54: 700-713
- Contribution of a genetic risk score to clinical prediction of hepatic steatosis in obese children and adolescents.Dig Liver Dis. 2019; (in press)
- Leptin, free leptin index, insulin resistance and liver fibrosis in children with non-alcoholic fatty liver disease.Eur J Endocrinol. 2006; 155: 735-743
- Classification and diagnosis of diabetes: standards of medical care in diabetes-2019.Diabetes Care. 2019; 42: S13-S28
- Waist circumference correlates with liver fibrosis in children with non-alcoholic steatohepatitis.Gut. 2008; 57: 1283-1287
- Nonalcoholic Steatohepatitis Clinical Research Network. Design and validation of a histological scoring system for nonalcoholic fatty liver disease.Hepatology. 2005; 41: 1313-1321
- Development and validation of a new histological score for pediatric non-alcoholic fatty liver disease.J Hepatol. 2012; 57: 1312-1318
- I148M patatin-like phospholipase domain-containing 3 gene variant and severity of pediatric nonalcoholic fatty liver disease.Hepatology. 2010; 52: 1274-1280
- Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease.Nat Genet. 2008; 40: 1461-1465
- Genetic factors that affect risk of alcoholic and nonalcoholic fatty liver disease.Gastroenterology. 2016; 150: 1728-1744
- The burden of diabetes mellitus among US youth: prevalence estimates from the SEARCH for Diabetes in Youth Study.Pediatrics. 2006; 118: 1510-1518
- Fasting plasma glucose (FPG) and the risk of impaired glucose tolerance in obese children and adolescents.Obesity (Silver Spring). 2010; 18: 1437-1442
- Screening for impaired glucose tolerance in obese children and adolescents: a validation and implementation study.Pediatr Obes. 2014; 9: 17-25
- CARdiometabolic risk factors in overweight and obese children in ITALY” (CARITALY) Study Group. Impaired fasting glucose and impaired glucose tolerance in children and adolescents with overweight/obesity.J Endocrinol Invest. 2017; 40: 409-416
- The genetic backgrounds in nonalcoholic fatty liver disease.Clin J Gastroenterol. 2018; 11: 97-102
- Maturity-onset diabetes of the young (MODY): how many cases are we missing?.Diabetologia. 2010; 53: 2504-2508
Article info
Publication history
Published online: July 04, 2019
Accepted:
June 25,
2019
Received in revised form:
June 14,
2019
Received:
March 21,
2019
Identification
Copyright
© 2019 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
