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Parallel to the dramatic rise of pediatric obesity, estimates reported an increased prevalence of type 2 diabetes (T2D) already in childhood. The close relationship between obesity and T2D in children is mainly sustained by insulin resistance (IR). In addition, the cardiometabolic burden of T2D including nonalcoholic fatty liver disease, cardiovascular disease and metabolic syndrome is also strictly related to IR. Although T2D pathophysiology has been largely studied in an attempt to improve therapeutic options, molecular mechanisms are still not fully elucidated. In this perspective, omics approaches (including lipidomics, metabolomics, proteomics and metagenomics) are providing the most attractive therapeutic options for T2D. In particular, distinct both lipids and metabolites are emerging as potential therapeutic tools. Of note, among lipid classes, the pathogenic role of ceramides in T2D context has been supported by several data. Thus, selective changes of ceramides expression might represent innovative therapeutic strategies for T2D treatment. More, distinct metabolomics pathways have been also found to be associated with higher T2D risk, by providing novel potential T2D biomarkers. Taken together, omics data are responsible for the expanding knowledge of T2D pathophysiology, by providing novel insights to improve therapeutic strategies for this tangled disease. We aimed to summarize the most recent evidence in the intriguing field of the omics approaches in T2D both in adults and children.

The coronavirus disease 2019 (COVID-19) pandemic changed adults and children’s lifestyle. We focused our attention on children affected by chronic kidney disease (CKD) due to congenital abnormalities of kidney and urinary tract (CAKUT) and their behavior during the lockdown. Our aims were to evaluate the incidence of CKD progression within 6 months after the end of the first Italian lockdown and the factors associated to it. CKD progression was defined by the transition to higher CKD stage or by the drop in estimated glomerular filtration rate by a 25% or more for patients belonging to CKD stages 1 and 2. We retrospectively selected 21 children with CAKUT and CKD ≥ stage 1 observed within 3 months before and 6 months after the first Italian lockdown. We called them by phone and asked them about their lifestyle before and during lockdown focusing on physical activity, screen time, sweet/candies/sugar-sweetened beverages eaten/drunk and adherence to the Mediterranean diet (MD) (through KIDMED questionnaire). We calculated and analyzed the delta between the pre- and post- lockdown observation of all collected parameters (clinical and biochemical parameters and questionnaires scores). Analyzing the overall cohort, we found significantly increased mean BMI and mean screen time and significantly lower mean physical activity time in post- compared with pre-lockdown observations. Eleven out of twenty-one patients (52.4%) had a worsening of CKD. These patients presented higher delta of levels of uric acid and microalbuminuria and showed minor adherence to the MD and declared to have consumed more sweets or candies or sugar-sweetened beverages/week during the lockdown with a tendentially major increment of BMI compared with patients not presenting CKD progression. In conclusion, the lockdown for COVID-19 pandemic determined increase of BMI in all enrolled patients due to a “forced” negative lifestyle. About half of these patients presented CKD progression. This progression was associated to less adherence to the MD and major consumption of sweets or candies or sugar-sweetened beverages.

Introduction: Over the past decades, a large amount of both adult and pediatric data has shown relationship between Nonalcoholic Fatty Liver Disease (NAFLD) and chronic kidney disease (CKD), resulting in an overall increased cardiometabolic burden. In view of the remarkable role of the genetic background in the NAFLD pathophysiology, a potential influence of the major NAFLD polymorphisms (e.g. the I148M variant of the Patatin-like phospholipase containing domain 3 (PNPLA3) gene, the E167K allele of the Transmembrane 6 superfamily member 2 (TM6SF2), the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), and the Membrane bound O-acyltransferase domain containing 7-transmembrane channel-like 4 (MBOAT7-TMC4) genes) on renal function has been supposed. A shared metabolic and proinflammatory pathogenesis has been hypothesized, but the exact mechanism is still unknown. Areas covered: We provide a comprehensive review of the potential genetic link between NAFLD and CKD in children. Convincing both adult and pediatric evidence supports this association, but there is some dispute especially in childhood. Expert opinion: Evidence supporting a potential genetic link between NAFLD and CKD represents an intriguing aspect with a major clinical implication because of its putative role in improving strategy programs to counteract the higher cardiometabolic risk of these patients.

Background Growing evidence supports a genetic link between non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). Interesting data demonstrated that both the major NAFLD risk polymorphisms such as the I148M polymorphism in the patatin like phospholipase containing domain 3 (PNPLA3) and the E167K allele in the transmembrane 6 superfamily member 2 gene (TM6SF2) affect renal function. Recently the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) gene has been recognized as a novel genetic variant involved in NAFLD pathophysiology. In particular, it has been showed the protective effect of the rs72613567:TA variant of this gene against liver damage both in adults and children. Aim To investigate the impact of the rs72613567:TA variant of the HSD17B13 gene on estimated glomerular filtration rate (eGFR) in obese children. Methods We enrolled 684 obese children (mean age 10.56 ± 2.94 years; mean BMI-SDS 2.98 ± 0.78) consecutively attending our Obesity Clinic. All the patients underwent a careful clinical assessment and a comprehensive biochemical evaluation. To detect hepatic steatosis, a liver ultrasound was performed. NAFLD was defined by ultrasound detected liver steatosis and/or alanine aminotransferase (ALT) levels > 40 IU/L. The study population was divided on the basis of the NAFLD presence. Genotyping for the rs72613567:TA variant of the HSD17B13 gene in all the enrolled subjects was also made. Results Patients carrying the HSD17B13 rare A allele showed higher eGFR levels compared with homozygous patients both among subjects with and without NAFLD. A general linear model confirmed a direct and significant association of eGFR values with HSD17B13 genotype independently of PNPLA3 and TM6SF2 polymorphisms both in patients with and without NAFLD. A comparison of regression line confirmed the influence of HSD17B13 genotype on the relationship between eGFR and age both among patients with and without NAFLD. Homozygous patients for HSD17B13 genotype with NAFLD showed a significantly higher decline of eGFR with the increase of the age compared with the patients with NAFLD carrying the HSD17B13 rare A allele (P value for intercepts = 0.005; P value for slopes = 0.94). The same effect was observed among patients without NAFLD (P value for intercepts = 0.0012; P value for slopes = 0.87). Conclusion Carriers of the HSD17B13 rare A allele showed higher eGFR levels than homozygous subjects both among subjects with and without NAFLD and independently of PNPLA3 I148M and TM6SF6 E167K polymorphisms.