Effects of Dietary Sugar Reduction on Biomarkers of Cardiometabolic Health in Latino Youth: Secondary Analyses from a Randomized Controlled Trial.

Pediatric obesity and cardiometabolic disease disproportionately impact minority communities. Sugar reduction is a promising prevention strategy with consistent cross-sectional associations of increased sugar consumption with unfavorable biomarkers of cardiometabolic disease. Few trials have tested the efficacy of pediatric sugar reduction interventions. Therefore, in a parallel-design trial, we randomized Latino youth with obesity (BMI ≥ 95th percentile) [n = 105; 14.8 years] to control (standard diet advice) or sugar reduction (clinical intervention with a goal of ≤10% of calories from free sugar) for 12-weeks. Outcomes included changes in glucose tolerance and its determinants as assessed by a 2-h frequently sample oral glucose tolerance test, fasting serum lipid profile (total cholesterol, HDL, LDL, triglycerides, cholesterol:HDL), and inflammatory markers (CRP, IL-6, TNF-α). Free sugar intake decreased in the intervention group compared to the control group [11.5% to 7.3% vs. 13.9% to 10.7% (% Energy), respectively, p = 0.02], but there were no effects on any outcome of interest (pall > 0.07). However, an exploratory analysis revealed that sugar reduction, independent of randomization, was associated with an improved Oral-disposition index (p < 0.001), triglycerides (p = 0.049), and TNF-α (p = 0.02). Dietary sugar reduction may have the potential to reduce chronic disease risks through improvements in beta-cell function, serum triglycerides, and inflammatory markers in Latino adolescents with obesity.

Clinical Intervention to Reduce Dietary Sugar Does Not Affect Liver Fat in Latino Youth, Regardless of PNPLA3 Genotype: A Randomized Controlled Trial.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) among Latinos is partially attributed to a prevalent C>G polymorphism in the patatin-like phospholipase 3 (PNPLA3) gene. Cross-sectional analyses in Latino children showed the association between dietary sugar and liver fat was exacerbated by GG genotype. Pediatric feeding studies show extreme sugar restriction improves liver fat, but no prior trial has examined the impact of a clinical intervention or whether effects differ by PNPLA3 genotype. OBJECTIVES: We aimed to test effects of a clinical intervention to reduce dietary sugar compared with standard dietary advice on change in liver fat, and secondary-endpoint changes in liver fibrosis, liver enzymes, and anthropometrics; and whether effects differ by PNPLA3 genotype (assessed retrospectively) in Latino youth with obesity (BMI ≥ 95th percentile). METHODS: This parallel-design trial randomly assigned participants (n = 105; mean baseline liver fat: 12.7%; mean age: 14.8 y) to control or sugar reduction (goal of ≤10% of calories from free sugar) for 12 wk. Intervention participants met with a dietitian monthly and received delivery of bottled water. Changes in liver fat, by MRI, were assessed by intervention group via general linear models. RESULTS: Mean free sugar intake decreased in intervention compared with control [11.5% to 7.3% compared with 13.9% to 10.7% (% energy), respectively; P = 0.02], but there were no significant effects on liver outcomes or anthropometrics (Pall > 0.10), and no PNPLA3 interactions (Pall > 0.10). In exploratory analyses, participants with whole-body fat mass (FM) reduction (mean ± SD: -1.9 ± 2.4 kg), irrespective of randomization, had significant reductions in liver fat compared with participants without FM reduction (median: -2.1%; IQR: -6.5% to -0.8% compared with 0.3%; IQR: -1.0% to 1.1%; P < 0.001). CONCLUSIONS: In Latino youth with obesity, a dietitian-led sugar reduction intervention did not improve liver outcomes compared with control, regardless of PNPLA3 genotype. Results suggest FM reduction is important for liver fat reduction, confirming clinical recommendations of weight loss and a healthy diet for pediatric NAFLD.This trial was registered at clinicaltrials.gov as NCT02948647.

Nonalcoholic fatty liver disease in pediatric patients.

Nonalcoholic fatty liver disease is a spectrum of liver disease ranging from simple hepatic steatosis to steatohepatitis, hepatic fibrosis, and cirrhosis. It is highly associated with obesity and insulin resistance, and with the dramatic increase in childhood and adolescent obesity, it has become the most common form of chronic liver disease in these age groups. Genetic and environmental factors both appear to play a role in the development of nonalcoholic fatty liver disease. There is currently no established effective therapy, and decreasing the prevalence of this disorder will require a reduction in the current obesity epidemic.

Isoniazid-related hepatic failure in children: a survey of liver transplantation centers.

BACKGROUND: Isoniazid (INH) therapy for tuberculosis carries a known risk for hepatoxicity, and leads to hepatic failure in a small subset of patients. This incidence has been described for adults, but is uncertain in children. Our aim was to estimate the incidence of pediatric referrals for INH-related liver failure, and to describe the characteristics and outcomes of these patients. METHODS: The 84 U.S. centers performing pediatric liver transplants between 1987 and 1997 were surveyed regarding patients with INH-induced liver failure. Additional transplant statistics were obtained from the United Network for Organ Sharing. Estimates of the number of children taking preventive INH were derived from a nationwide public health database. RESULTS: Twenty cases of INH-related liver failure were found during a 10-year period. Four patients (20%) recovered spontaneously; 10 (50%) underwent orthotopic liver transplantation (OLT), while six (30%) died awaiting OLT. Mean age at presentation was 9.8 years (range 1.3-17). Mean length of INH therapy was 3.3 months (range 0.5-9). Notably, five patients seen for symptoms of hepatitis were initially told not to stop treatment. INH-associated liver failure accounted for 0.2% (8 of 4679) of all pediatric OLTs, and 14% (8/56) of transplants for drug hepatoxicity. The estimated incidence of liver failure was up to 3.2/100,000 for children on prophylactic INH. CONCLUSIONS: While INH-associated liver failure in children is rare, discontinuation at the onset of symptoms does not assure recovery. This indicates a need for increased awareness of hepatotoxicity risk, expanded biochemical monitoring for children receiving INH, and prompt withdrawal in symptomatic patients.