1 Hepatology, Gastroenterology and Nutrition Unit, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy; Department of Pediatric, University "La Sapienza", Rome, Italy.
2 Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
3 Dipartimento Pediatrico Universitario Ospedaliero "Bambino Gesù" Children's Hospital-IRCCS, "Tor Vergata" University, Rome, Italy; Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
4 Research Unit of Molecular Genetics of Complex Phenotypes, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy.
5 Hepatology, Gastroenterology and Nutrition Unit, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy.
6 Hepato-Metabolic Disease Unit, "Bambino Gesù" Children's Hospital, IRCCS, Rome, Italy.
7 Pediatric Diabetes and Metabolic Disorders Unit, Department of Surgery, Dentistry, Pediatrics and Gynaecology, University Hospital of Verona, Verona, Italy.
8 NAFLD Research Center, Division of Gastroenterology, University of California, San Diego, CA, United States.
9 Nutrition and Metabolism, Faculty of Medicine, University of Southampton, Southampton, UK; Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Southampton SO16 6YD, UK.
10 Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy. Electronic address: firstname.lastname@example.org.
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.
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.
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.
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.
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.