Uric acid and gamma-glutamyl-transferase in children and adolescents with obesity: Association to anthropometric measures and cardiometabolic risk markers depending on pubertal stage, sex, degree of weight loss and type of patient care: Evaluation of the adiposity patient follow-up registry.

OBJECTIVES: Associations between body mass index (BMI)- standard deviation score (SDS)/waist-to-height ratio (WHtR) were studied with (i) serum uric acid (sUA)/gamma-glutamyl-transferase (GGT) and (ii) cardiometabolic risk markers in children with obesity, considering sex, pubertal development, and degree of weight loss/type of patient care. METHODS: 102 936 children from the Adiposity-Follow-up registry (APV; 47% boys) were included. Associations were analysed between sUA/GGT and anthropometrics, transaminases, lipids, fasting insulin (FI), homeostasis model assessment of insulin resistance (HOMA-IR), triglycerides to HDL-cholesterol (TG/HDL)-ratio. Follow-up analyses (3-24 months after baseline) considered a BMI-SDS reduction ≥0.2 (n = 11 096) or ≥0.5 (n = 3728). Partialized correlation analyses for sex and BMI-SDS were performed, taking pubertal development into consideration. RESULTS: At baseline, BMI-SDS showed the strongest correlations to sUA (r = 0.35; n = 26 529), HOMA-IR/FI (r = 0.30; n = 5513 /n = 5880), TG/HDL-ratio (r = 0.23; n = 24 501), and WHtR to sUA (r = 0.32; n = 10 805), GGT (r = 0.34; n = 11 862) and Alanine-aminotransferase (ALAT) (r = 0.33; n = 11 821), with stronger correlations in boys (WHtR and GGT: r = 0.36, n = 5793) and prepubertal children (r = 0.36; n = 2216). GGT and sUA (after partializing effects of age, sex, BMI-SDS) showed a correlation to TG/HDL-ratio (r = 0.27; n = 24 501). Following a BMI-SDS reduction ≥0.2 or ≥0.5, GGT was most strongly related to Aspartate-aminotransferase (ASAT)/ ALAT, most evident in prepuberty and with increasing weight loss, and also to TG/HDL-ratio (r = 0.22; n = 1528). Prepubertal children showed strongest correlations between BMI-SDS/WHtR and GGT. ΔBMI-SDS was strongly correlated to ΔsUA (r = 0.30; n = 4160) and ΔGGT (r = 0.28; n = 3562), and ΔWHtR to ΔGGT (r = 0.28; n = 3562) (all p < 0.0001). CONCLUSION: Abdominal obesity may trigger hyperuricemia and hepatic involvement already in prepuberty. This may be stronger in infancy than anticipated to date. Even moderate weight loss has favourable effects on cardiometabolic risk profile and glucose homeostasis.

Diabetic ketoacidosis in pediatric patients with type 1- and type 2 diabetes during the COVID-19 pandemic.

BACKGROUND: COVID-19 pandemic caused families to stay home and cancel everyday activities. Hospital admissions decreased, affecting changes in diagnoses and management of chronic disease in children. AIMS: We analyzed how the first lockdown influenced clinical presentation and manifestation of children with diabetes mellitus (DM) in a German University Hospital. METHODS: During March 15th and October 11th 2020, data on general patient information, clinical symptoms and on lab results related to diabetic ketoacidosis (DKA) were analyzed in children (0-18 years) who presented with new onset of DM or poor metabolic control of known DM. All data including frequency and severity of DKA were compared to data from patients who presented in 2019. RESULTS: Data from 125 participants with DM were evaluated (2020: n = 52; 2019: n = 73). In 2020, twelve patients (23.1%) were diagnosed with new onset DM, two of them with type2 diabetes, and 66.7% presented with DKA including both patients T2DM. In 2019, 24.5% of patients had new onset DM, and 50% of them presented with DKA. In 2020, patients with new onset DM were younger, presented with more severe symptoms of DKA and had to stay longer in hospital compared to 2019. In 2020, six children (50%) with new onset DM were <6 years, whereas in 2019 most children with new onset DM were adolescents (n = 7, 38.9%). CONCLUSION: COVID-19 lockdown aggravated complications of diabetes onset and therapy management, including severity and frequency of DKA. It underlines the need of health education for early DKA diagnosis to early identify children at risk.

Childhood Obesity and Cancer Risk in Adulthood.

PURPOSE OF REVIEW: The purpose of this review is to summarize our current understanding of the association between childhood obesity and cancer risk later in life. RECENT FINDINGS: Adipose tissue secrets a variety of adipocytokines, and expression and/or secretion rate of most of them seems to be increased or dysregulated in obesity. In addition, obesity leads to increased secretion of proinflammatory cytokines such as interferon-γ (IFN-γ), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α), which promotes an infiltration of inflammatory immune cells into adipose tissue. This process may facilitate a state of "subclinical inflammation" (metaflammation) and may lead to the development of the metabolic syndrome (MetS), starting as early as during childhood. In addition, several oncogenes have been linked to inflammation and cancer development via different pathways, and several types of tumors need an inflammatory environment before a malignant change occurs. An inflammatory environment seems to promote the proliferation and survival of malignant cells as well as angiogenesis. Natural killer (NK) cells play an important role in this process, as they are able to kill transformed cells without prior sensitization and coordinate subsequent immune responses by producing distinct cytokines, thus providing antitumor immunity. First studies in children have suggested that NK cells from obese children are activated, metabolically stressed, and functionally deficient. This may lead to a suppression of antitumor immunity as early as during childhood, probably many years before the development of cancer. Epidemiological studies have shown a strong association between higher body mass index (BMI) during childhood and adolescence and increased risk for several malignancies in adulthood, including leukemia, Hodgkin's disease, colorectal cancer, and breast cancer. Underlying mechanisms are not completely understood, but several adipocytokines and inflammatory markers including NK cells seem to be "key players" in this process.

Metabolic Syndrome in Children and Adolescents: Diagnostic Criteria, Therapeutic Options and Perspectives.

PURPOSE OF REVIEW: This review summarizes our current understanding of the metabolic syndrome (MetS) in children and adolescents. Special emphasis is given towards diagnostic criteria and therapeutic options. RECENT FINDINGS: Consistent diagnostic criteria to define MetS in childhood and adolescence are not available to date. There is common agreement that the main features defining MetS include (1) disturbed glucose metabolism, (2) arterial hypertension, (3) dyslipidemia, and (4) abdominal obesity. However, settings of cut-off values are still heterogeneous in the pediatric population. Additional features that may define cardiometabolic risk, such as non-alcoholic fatty liver disease (NAFDL) or hyperuricemia, are not considered to date. Prevalence of childhood obesity has more than doubled since 1980, and 6-39% of obese children and adolescents already present with MetS, depending on the definition applied. There is common agreement that a consistent definition of MetS is urgently needed for children to identify those at risk as early as possible. Such definition criteria should consider age, gender, pubertal stage, or ethnicity. Additional features such as NAFDL or hyperuricemia should also be included in MetS criteria. Lifestyle modification is still the main basis to prevent or treat childhood obesity and MetS, as other therapeutic options (pharmacotherapy, bariatric surgery) are not available or not recommended for the majority of affected youngster.