Lipid profile in Noonan syndrome and related disorders: trend by age, sex and genotype.

Background: RASopathies are developmental disorders caused by dysregulation of the RAS-MAPK signalling pathway, which contributes to the modulation of multiple extracellular signals, including hormones and growth factors regulating energetic metabolism, including lipid synthesis, storage, and degradation. Subjects and methods: We evaluated the body composition and lipid profiles of a single-centre cohort of 93 patients with a molecularly confirmed diagnosis of RASopathy by assessing height, BMI, and total cholesterol, HDL, triglycerides, apolipoprotein, fasting glucose, and insulin levels, in the context of a cross sectional and longitudinal study. We specifically investigated and compared anthropometric and haematochemistry data between the Noonan syndrome (NS) and Mazzanti syndrome (NS/LAH) groups. Results: At the first evaluation (9.5 ± 6.2 years), reduced growth (-1.80 ± 1.07 DS) was associated with a slightly reduced BMI (-0.34 DS ± 1.15 DS). Lipid profiling documented low total cholesterol levels (< 5th percentile) in 42.2% of the NS group; in particular, in 48.9% of PTPN11 patients and in 28.6% of NS/LAH patients compared to the general population, with a significant difference between males and females. A high proportion of patients had HDL levels lower than the 26th percentile, when compared to the age- and sex-matched general population. Triglycerides showed an increasing trend with age only in NS females. Genotype-phenotype correlations were also evident, with particularly reduced total cholesterol in about 50% of patients with PTPN11 mutations with LDL-C and HDL-C tending to decrease during puberty. Similarly, apolipoprotein A1 and apolipoprotein B deficits were documented, with differences in prevalence associated with the genotype for apolipoprotein A1. Fasting glucose levels and HOMA-IR were within the normal range. Conclusion: The present findings document an unfavourable lipid profile in subjects with NS, in particular PTPN11 mutated patients, and NS/LAH. Further studies are required to delineate the dysregulation of lipid metabolism in RASopathies more systematically and confirm the occurrence of previously unappreciated genotype-phenotype correlations involving the metabolic profile of these disorders.

A comparative study on the incidence of type 1 diabetes mellitus between children of North African migrants and Italian children in Emilia-Romagna region, Italy.

In the last few decades, many studies have reported an increasing global incidence of type 1 diabetes. Studies on migrant populations have underlined the importance of both environmental and genetic factors. AIMS: Evaluate the incidence of type 1 diabetes in North African vs Italian children aged 0-14 years from 1 January 2015, to 31st December 2018, in Emilia-Romagna region, Italy. METHODS: Clinical and epidemiological data about childhood onset type 1 diabetes in Emilia Romagna region were retrospectively collected by the regional centers of pediatric diabetology and matched using 3 different data sources. RESULTS: 365 new cases were diagnosed. Total cumulative incidence was 15.4/100,000/year. North African cases showed a cumulative incidence of 53.8/100,000/year, statistically significant compared to cumulative incidence of the Italian cases alone 13.1/100,000/year (p value < 0.001). The annual incidence did not differ in the 4 years for both groups.  Conclusion: The incidence of type 1 diabetes in the pediatric age (0 14 years) was significantly higher in the North African population than in the Italian one, suggesting that a mix of genetic and environmental factors may have caused the increase in newly diagnosed cases. WHAT IS KNOWN: • The incidence of type 1 diabetes largely varies worldwide. • Study on immigrants helped to better understand the interplay role between genetics and environment. WHAT IS NEW: • This is the first study focused on the incidence of children and adolescents of North African migrants in Italy. • The incidence of children and adolescents of North African migrants in Emilia Romagna region, Italy, seems to be higher than that reported in the host countries, and, above all, than that reported in highest-incidence countries in Europe and in the world.

Gender differences in weight gain during lockdown due to COVID-19 pandemic in adolescents with obesity.

BACKGROUND AND AIM: Lockdown due to COVID-19 pandemic has forced a decrease in physical activity (PA), an increase in sedentary behavior (SB) and a possibly worsening of fat accumulation in already obese subjects. The aim of this study was to investigate how social restriction may have contributed to weight changes in adolescents with obesity. Secondary aim was to evaluate possible parameters influencing weight changes. METHODS AND RESULTS: Parameters of 51 obese adolescents were compared between two visits: within 2 months before 8 March, start of lockdown, and within 40 days after the end of it. RESULTS: Mean weight gain during lockdown was 2.8 ± 3.7 kg (p < 0.001). Weight increase was higher in males than in females (3.8 ± 3.4 kg vs 1.2 ± 3.7 kg, p = 0.02). The hours dedicated to SB increased (+2.9 ± 2.8 h/day; p < 0.001) while the hours of PA decreased (-1.0 ± 1.6 h/week; p < 0.001). Males spent more hours in SB than females (+3.8 ± 2.7 h/day vs +1.5 ± 2.5 h/day; p = 0.003). There were minor changes in diet during lockdown. The most significant variables influencing both delta BMI and waist/height ratio increase were hours devoted to SB during lockdown and differences in mild and moderate PA before and after lockdown. CONCLUSIONS: Obese adolescents showed a worsening of obesity during lockdown, with males mainly affected, mainly due to a reduced mild PA and increased hours spent in SB.

Adolescents with severe obesity show a higher cardiovascular (CV) risk than those with type 1 diabetes: a study with skin advanced glycation end products and intima media thickness evaluation.

AIMS: Type 1 diabetes (T1D) and obesity are strongly associated with cardiovascular (CV) risk and can start in the paediatric age. The CV risk profile of two groups of adolescents was compared through the evaluation of sAGE, IMT and known variables associated with CV risk. The first group was affected by T1D with duration of disease of at least 5 years or 3 years since puberty onset, and the second by severe obesity for more than 3 years. METHODS: A total of 116 patients were prospectively enrolled in the study (71 T1D, 33 males and 38 females; 45 obese, 18 males and 27 females), and their sAGE, IMT, waist/height ratio, LDL cholesterol, triglycerides/cholesterol HDL ratio, BMI, HbA1c and blood pressure were measured. RESULTS: An IMT value > 0.7 mm, cut-off value to define CV risk, was present in 28% of the obese patients and in no T1D patients. Age-adjusted sAGE and HbA1c levels were higher T1D patients, whereas a higher percentage of pathological values was present in most of the remaining studied variables. In T1D patients, there was a higher percentage of females with waist/height ratio > 0.5, LDL cholesterol > 100 mg/dL, triglycerides/HDL cholesterol ratio > 2 and BMI > 99° centile and a higher percentage of males with HbA1c > 7%. On the contrary, in obese patients there were no differences between males and females. Multiple analysis is identified BMI SDS as the only variable with a significant influence on IMT in both groups. Furthermore, it showed that HbA1c and gender affected sAGE in T1D patients, whereas only age and gender in the obese patients. CONCLUSIONS: Our study demonstrates that our adolescents with severe obesity carry a much higher CV risk than adolescents with T1D unless in bad metabolic control. Apart from lower sAGE levels, most of the variables considered to define CV risk were higher in the obese group than in the T1D group. Gender seems to have a significant impact on sAGE levels but not on IMT.

Whole lipid profile and not only HDL cholesterol is impaired in children with coexisting type 1 diabetes and untreated celiac disease.

AIMS: Low HDL cholesterol (HDL-C) levels have been described in patients with coexisting type 1 diabetes mellitus (T1DM) and celiac disease (CD). Data on other possible lipid abnormalities that could further increase cardiovascular risk in these patients are scarce and incomplete. Aim of this retrospective multicenter study was to evaluate whole lipid profiles, besides HDL-C, in children with T1DM associated with biopsy-proven CD, and to investigate the influence of age and degree of adherence to gluten-free diet (GFD) on lipid changes. METHODS: A total of 261 children with both T1DM and CD were enrolled. Serum lipid profiles at CD diagnosis were compared with those after 1 year of GFD and with those of 224 matched children with T1DM alone. The adherence to GFD was judged by means of CD-related antibodies. RESULTS: At CD diagnosis, children with T1DM + CD showed higher LDL cholesterol (LDL-C) compared to children with T1DM alone. Gluten withdrawal failed to normalize LDL-C levels, not even in completely adherent individuals. HbA1c values were not influenced by GFD. The youngest children were characterized at diagnosis by lower levels of total cholesterol and on treatment by a greater decrease in triglycerides levels. CONCLUSIONS: An unfavorable lipid profile, characterized not only by low HDL-C levels but also by high LDL-C values, may increase the risk of cardiovascular disease in children with T1DM and untreated CD. Therefore, a strict gluten-free diet is mandatory in these children, especially the youngest.