Effects of COVID-19 time on the development of pre-impaired glucose tolerance state in children and adolescents with overweight and obesity.

OBJECTIVES: We aimed to characterize the effects of COVID-19 Pandemic on 2 h plasma glucose (2 h PG) values after an OGTT postulating a correlation between 2 h PG spectrum and the decline of ß-cell function. Particularly, we tried to evaluate the effects on the risk of showing 2 h plasma glucose values in the highest range of normal values in children and adolescent with obesity during COVID-19 Pandemic compared to those evaluated during the 13 years before. SUBJECTS/METHODS: Data from 532 children and adolescents with obesity and overweight (before COVID-19 Pandemic, 209M/262F, 2008-2019; during COVID-19 Pandemic, 40M/21F, 2020-2021) who had undergone a complete evaluation and had performed an OGTT were analyzed. The two groups were further divided into three sub-groups based on the 2 h PG, group 1 (2 h PG < 5.55 mmol/L), group 2 (5.56 < 2 h PG < 6.60 mmol/L), group 3 (6.61 < 2h PG < 7.72 mmol/L), respectively. The prevalence of 2 h PG values distribution in children was evaluated between before and during COVID-19 Pandemic period and the main differences between the two groups 3 of each period were analyzed. RESULTS: A significant difference (P = 0.01) in terms of distribution of the prevalence of 2h PG values was documented between the group before COVID-19 (35.6%, 45.9% and 18.5%) and the group during COVID-19 Pandemic (31.1%, 31.1% and 37.8%). A roughly doble higher prevalence of subjects with pre-IGT was documented in the COVID-19 group. In addition, group 3 of COVID-19 time showed significantly higher values for waist circumference (WC), Waist/Height ratio (WtHR), fasting glucose and HOMA-IR compared to the group 3 of the period before COVID-19 Pandemic (all P < 0.05). CONCLUSIONS: During COVID-19 time a higher percentage of children are in the highest range of normal 2 h PG values which is known to be associated with a significant impairment of ß-cell function and insulin sensitivity and have higher risk of developing IGT.

The bad rainbow of COVID-19 time: effects on glucose metabolism in children and adolescents with obesity and overweight.

BACKGROUND: COVID-19 restriction measurements have enhanced the obesity status in the pediatric population which might further contribute to obesity-related glucose-insulin metabolism alterations. Therefore, we retrospectively compared anthropometric and OGTT data on children with obesity during the 13 years before and during the COVID-19 pandemic. SUBJECTS/METHODS: Data from 741 children with obesity and overweight were retrieved and clustered into seven groups starting from year 2008-2009 until 2020-2021. Differences in anthropometric measurements and glucose/insulin metabolism were evaluated between the different groups. RESULTS: Children with overweight and obesity in the COVID-19 restriction group did not present increased values of SDS-Body Mass Index (BMI). Significantly higher values for Waist Circumference (WC), SDS-WC, Waist/Height ratio (WHtR), and body mass fat were detected in these children (all P < 0.01). Fasting glycaemia, glucose, and insulin excursions were significantly higher compared to pre- pandemic children (all P < 0.01). Insulin resistance was higher while insulin secretion was lower (all P < 0.01) determining a significantly higher percentage of impaired glucose tolerance in the COVID-19 restriction group (P < 0.002). Furthermore, High-Density Lipoprotein (HDL) cholesterol was significantly lower (P < 0.01) and SDS for systolic and diastolic blood pressure values were significantly higher (P = 0.03 and P = 0.02, respectively). CONCLUSIONS: COVID-19 restriction measurements determined profound alterations in glucose and insulin metabolism in children with obesity and overweight. Urgent strategies are needed in order to reverse COVID-19 restriction measures' effects on glucose and insulin metabolism.

Insulin resistance relates to DKA severity and affects insulin requirement in children with type 1 diabetes at onset.

BACKGROUND: Fluid and insulin treatments are the cornerstones of DKA management and indications on dosages are available. However, according to possible confounding factors, relevant data are still required to explain the different insulin dosages adopted at diabetes onset, particularly based upon insulin sensitivity. OBJECTIVE: We aimed to explore whether DKA severity is related to different insulin sensitivity states, thus resulting in different insulin requirement at diabetes onset. METHODS: Retrospective data from hospital records of 62 newly diagnosed children with type 1 diabetes with DKA were analyzed. The population was divided into three groups: severe, moderate, and mild DKA. Anthropometric, laboratory test, insulin, and glucose administration data were analyzed. The Glucose Infusion Rate (GIR), Insulin Infusion Rate (IIR), and GIR/IIR were calculated and used as indexes of insulin sensitivity. The area under the curve (AUC) for insulin and glucose infusion was calculated. RESULTS: Moving among the three groups, IIR decreased while GIR and GIR/IIR increased from severe to mild DKA group (all p < 0.01). A similar trend was documented for AUC-insulin and AUC-glucose as well as AUC-glucose/AUC-insulin ratio. The Spearman correlation showed a negative correlation between pH and both IIR and AUC-Insulin as well as a positive correlation between pH and both GIR/IIR and AUC-glucose/AUC-insulin ratio. CONCLUSIONS: Subjects with severe DKA have a higher insulin requirement compared to those with less severe DKA. Significant differences in terms of insulin sensitivity might be documented according to the severity of DKA, which might result in tailored insulin pH requirement in children with new onset type 1 diabetes.

Being born large for gestational age is associated with earlier pubertal take-off and longer growth duration: a longitudinal study.

AIM: Perinatal factors seem to influence the onset of puberty, but there is limited information on the potential effect of large size at birth on pubertal growth. This study evaluated pubertal growth in children born large for gestational age (LGA) compared to children born appropriate for gestational age (AGA). METHODS: Longitudinal growth data collected from 70 children - 40 AGA and 30 LGA - were analysed. The ages at take-off, peak height velocity, final height and pubertal growth spurts were calculated using the Preece-Baines model I. RESULTS: Large for gestational age children showed an earlier age at take-off compared to AGA children (10.1 ± 1.2 versus 11.0 ± 1.4 years, p = 0.007), whereas the age at peak height velocity and at final height was similar. LGA children showed a longer growth spurt duration (2.5 ± 1 versus 1.5 ± 1.2 years, p < 0.001) and total pubertal duration (5.3 ± 1.2 versus 4.6 ± 1.2 years, p = 0.036) than AGA children. Results were similar when stratified by sex. CONCLUSION: Being born LGA was associated with an earlier pubertal take-off and longer growth duration. These unique findings, due to the lack of studies on pubertal growth patterns in LGA children, might lead the way to novel research and a different approach to LGA children at the onset of pubertal growth.

Influence of inhaled corticosteroids on pubertal growth and final height in asthmatic children.

BACKGROUND: Controversial data exist on the possibility that inhaled corticosteroids (ICs) affect growth in children with mild-to-moderate asthma. We assessed whether ICs affect growth and final height (FH) in asthmatic children compared to controls. METHODS: A retrospective study was conducted on 113 asthmatic children compared with 66 control children. Asthmatic children presented with mild-to-moderate asthma and had exclusive ICs. Anthropometric data of four specific time-points were collected for both groups (pre-puberty, onset and late puberty, and FH) and converted to standard deviation scores (SDS). Growth trajectories were assessed as follows: (i) in puberty, using peak height velocity (PHV) and pubertal height gain SDS (PHG-SDS); (ii) until FH achievement, using FH-SDS and FH gain SDS (FHG-SDS). Repeated measurement analysis was performed across longitudinal study visits. A general linear model (GLM) was performed in asthmatic group evaluating the effect of corticosteroid type, treatment duration, and cumulative dose on FH corrected for multiple variables. RESULTS: At pre-puberty, height and weight SDS were similar between the groups (p > 0.05). Height SDS progressively declined over the study period in asthmatic patients from pre-puberty to FH (p-trend < 0.05), whereas it did not change over time in controls (p-trend > 0.05), in both boys and girls. Asthmatic children had exclusive ICs [budesonide (n = 36) vs. fluticasone (n = 43) vs. mometasone (n = 34)] for a mean period of 6.25 ± 1.20 years and a mean cumulative dose of 560.07 ± 76.02 mg. They showed decreased PHG-SDS and lower PHV compared to controls (all p < 0.05). FH-SDS and FHG-SDS were significantly reduced in asthmatic group compared to controls. FH in asthmatic patients was 2.5 ± 2.89 cm lower in boys and 2.0 ± 2.03 cm lower in girls than controls. The GLM showed that FH achievement was dependent on the type of ICs, duration of the treatment, and cumulative dose (p < 0.05). CONCLUSIONS: ICs affect pubertal growth determining reduced final height in asthmatic children compared to controls, in a dose- and duration-dependent manner.

The effect of obesity and type 1 diabetes on renal function in children and adolescents.

BACKGROUND: Early signs of renal complications can be common in youths with type 1 diabetes (T1D). Recently, there has been an increasing interest in potential renal complications associated with obesity, paralleling the epidemics of this condition, although there are limited data in children. HYPOTHESIS: Obese children and adolescents present signs of early alterations in renal function similar to non-obese peers with T1D. SUBJECTS: Eighty-three obese (age: 11.6 ± 3.0 yr), 164 non-obese T1D (age: 12.4 ± 3.2 yr), and 71 non-obese control (age: 12.3 ± 3.2 yr) children and adolescents were enrolled in the study. METHODS: Anthropometric parameters and blood pressure were measured. Renal function was assessed by albumin excretion rate (AER), serum cystatin C, creatinine and estimated glomerular filtration rate (e-GFR), calculated using the Bouvet's formula. RESULTS: Obese and non-obese T1D youths had similar AER [8.9(5.9-10.8) vs. 8.7(5.9-13.1) µg/min] and e-GFR levels (114.8 ± 19.6 vs. 113.4 ± 19.1 mL/min), which were higher than in controls [AER: 8.1(5.9-8.7) µg/min, e-GFR: 104.7 ± 18.9 mL/min]. Prevalence of microalbuminuria and hyperfiltration was similar between obese and T1D youths and higher than their control peers (6.0 vs. 8.0 vs. 0%, p = 0.02; 15.9 vs. 15.9 vs. 4.3%, p = 0.03, respectively). Body mass index (BMI) z-score was independently related to e-GFR (r = 0.328; p < 0.001), and AER (r = 0.138; p = 0.017). Hemoglobin A1c (HbA1c) correlated with AER (r = 0.148; p = 0.007) but not with eGFR (r = 0.041; p = 0.310). CONCLUSIONS: Obese children and adolescents show early alterations in renal function, compared to normal weight peers, and they have similar renal profiles than age-matched peers with T1D.

Spectrum of phenotypic anomalies in four families with deletion of the SHOX enhancer region.

BACKGROUND: SHOX alterations have been reported in 67% of patients affected by Léri-Weill dyschondrosteosis (LWD), with a larger prevalence of gene deletions than point mutations. It has been recently demonstrated that these deletions can involve the SHOX enhancer region, rather that the coding region, with variable phenotype of the affected patients.Here, we report a SHOX gene analysis carried out by MLPA in 14 LWD patients from 4 families with variable phenotype. CASE PRESENTATION: All patients presented a SHOX enhancer deletion. In particular, a patient with a severe bilateral Madelung deformity without short stature showed a homozygous alteration identical to the recently described 47.5 kb PAR1 deletion. Moreover, we identified, for the first time, in three related patients with a severe bilateral Madelung deformity, a smaller deletion than the 47.5 kb PAR1 deletion encompassing the same enhancer region (ECR1/CNE7). CONCLUSIONS: Data reported in this study provide new information about the spectrum of phenotypic alterations showed by LWD patients with different deletions of the SHOX enhancer region.

Skeletal muscle as a pro- and anti-inflammatory tissue: insights from children to adults and ultrasound findings.

Previously regarded as a movement and posture control agent, the skeletal muscle is now recognized as an endocrine organ that may affect systemic inflammation and metabolic health. The discovery of myokines such as IL-6, released from skeletal muscle in response to physical exercise, is now one of the most recent insights. Myokines are the mediators of the balance between the pro-inflammatory and anti-inflammatory responses. This underscores the muscle function as a determinant of good health and prevention of diseases. Advances in ultrasound technology improved evaluation of muscle thickness, composition, and determining fat distribution. Combining imaging with molecular biology, researchers discovered the complicated interplay between muscle function, cytokine production and general health effects.The production of myokines with exercise showcasing the adaptability of muscles to high-stress conditions and contributing to metabolism and inflammation regulation. These findings have significant implications in order to provide improvement in metabolic and inflammatory diseases.

Weight loss in obese prepubertal children: the influence of insulin resistance.

BACKGROUND: Insulin resistance (IR), a link of paramount importance between obesity and cardiovascular/metabolic complications, seems to be implicated in weight changes. OBJECTIVE: To determine whether IR could influence weight status during a 1-year intervention program in obese prepubertal children. METHODS: Forty-four children with IR (IR group) and 42 children without IR (NIR group) were enrolled. Body mass index standard deviation score (BMI-SDS), waist circumference (WC), and homeostasis model assessment (HOMA-IR) were evaluated. RESULTS: NIR children showed a significant reduction of BMI-SDS and WC at final assessment (p = 0.009 and p = 0.001, respectively), whereas IR children presented unchanged values. HOMA-IR decreased after intervention in the NIR group (p = 0.0008), but was exacerbated in IR children (p = 0.004). A positive and significant association between HOMA-IR at baseline and BMI at follow-up was found (B ± SE = 0.87 ± 0.24, p = 0.001). HOMA-IR at baseline was also significantly associated with WC at follow-up (B ± SE = 2.12 ± 0.69, p = 0.003). CONCLUSIONS: IR seems to influence adiposity changes in obese prepubertal children. Further longitudinal studies are needed to verify the relationship between IR and weight loss during childhood.

The possible role of esRAGE and sRAGE in the natural history of diabetic nephropathy in childhood.

The advanced glycation end products/receptor for advanced glycation end products (AGE-RAGE) pathway is a key mediator of glomerular changes in type 1 diabetes. We evaluated endogenous secretory (es)RAGE and soluble (s)RAGE concentrations in 64 pre-pubertal and pubertal normoalbuminuric patients with type 1 diabetes and compared the values with those of 62 controls matched for age, gender and Tanner pubertal stages. We also explored the possible association of their concentrations with early signs of diabetic nephropathy, defined as changes in kidney volume and estimated glomerular filtration rate (eGFR). Significantly lower concentrations of both esRAGE and sRAGE were documented in pre-pubertal (p = 0.003 and p = 0.001) and pubertal (p = 0.002 and p = 0.001) subjects with type 1 diabetes than in the controls. In both groups of patients with type 1 diabetes, the eGFR (pre-pubertal p = 0.01 and pubertal p = 0.01) and the mean value of kidney volume adjusted for body surface (pre-pubertal p = 0.003 and pubertal p = 0.002) were higher than those of the controls. The regression analysis showed an inverse relationship between esRAGE and body surface-adjusted mean kidney volume (p = 0.0004, r = -0.503). esRAGE and sRAGE concentrations were lower in normoalbuminuric youths with type 1 diabetes than in their healthy peers. The inverse association between esRAGE levels and early kidney alterations suggests a potential role of esRAGE in diabetic nephropathy.

Implications of gastrointestinal hormones in the pathogenesis of obesity in prepubertal children.

BACKGROUND: There is a worsening high prevalence of global obesity. Special attention has been paid to the gut-endocrine system, represented by the regulators of appetite. In particular, it has been suggested that ghrelin ("hunger" peptide), and obestatin and glucagon-like peptide-1 (GLP-1) ("satiety" peptides) could play important roles in the pathogenesis of obesity. OBJECTIVES: The aims of this study were to compare fasting plasma ghrelin, obestatin, and GLP-1 levels between obese and nonobese prepubertal children, and to assess their relations with fatness indexes and insulin resistance (IR). SUBJECTS AND METHODS: Fifty-two prepubertal obese children and 22 controls were enrolled. Fasting levels of gastrointestinal hormones (ghrelin, obestatin, and GLP-1), glucose, and insulin were evaluated. IR was assessed using the homeostasis model assessment of IR (HOMA-IR) index. Analysis was performed by Mann-Whitney U-test, Kruskal-Wallis test, and Spearman's correlation. RESULTS: Obese prepubertal children and normal-weight controls had similar age distribution. Obese children were more insulin resistant when compared to controls (HOMA-IR: p < 0.01 ). GLP-1 levels were significantly lower in obese children than in controls (p < 0.01). Obestatin was significantly higher in obese than normal-weight children (p < 0.01), while ghrelin was not different. There was a negative correlation between GLP-1 and standard deviation score-body mass index (r = -0.36, p = 0.009) and between GLP-1 and waist circumference (r = -0.45, p = 0.001), while no association was observed with HOMA-IR. CONCLUSIONS: GLP-1 levels have been shown to be correlated with adiposity indexes, but not with HOMA-IR, suggesting that this hormone could play an important role in the early development of obesity.

Growth failure in children with cystic fibrosis.

Poor linear growth and inadequate weight gain are very common problems in cystic fibrosis (CF) children. The most important factors involved in growth failure are undernutrition or malnutrition, chronic inflammation, lung disease, and corticosteroid treatment. Nutritional support and pharmacological therapy with recombinant human growth hormone are essential for a good management of children with CF, although these children are shorter and lighter than healthy children, and despite the catch-up growth observed after diagnosis, deficit in length/height and weight continues to be seen until adulthood. Early diagnosis is essential to ensure better nutritional status and growth, potentially associated with better respiratory function and prognosis. The aims of this review are try to explain etiology and pathogenetic mechanisms of growth failure in CF children and clarify their role in the disease morbidity and in clinical outcome, especially in relation to progressive decline of pulmonary function.

US in the diagnosis of gastroesophageal reflux in children.

Several techniques have been used to diagnose gastroesophageal reflux (GER) in children, but no single test is sufficiently accurate to completely investigate the problem. Gastroesophageal US has been described as a widely available, noninvasive and sensitive method. It provides morphological and functional information, but its role in the diagnosis of GER in children is still debated. In this paper we review diagnostic approaches to GER in children. We focus on current use of US in the management of children with suspected GER. Reports suggest that US allows exclusion of several non-GER causes of symptoms and that it provides morphological and functional data with high sensitivity and positive predictive value for the diagnosis of GER. Sonographic assessment of findings such as abdominal esophageal length, esophageal diameter, esophageal wall thickness and gastroesophageal angle provide important diagnostic indicators of reflux and related to the degree of GER. There is a need for standardization of the procedure and for defining diagnostic criteria.

A structured telephonic counselling to promote the exclusive breastfeeding of healthy babies aged zero to six months: a pilot study.

This pilot study aimed to test the effectiveness of a structured telephonic counselling (STC) on exclusive breastfeeding (EB) on healthy babies. The study was carried out on 114 primiparous women from February to March 2009. After randomization, women were divided into two groups: 55 receiving STC and 59 receiving conventional counselling. At 1, 3 and 5 months after delivery, a nurse specialist evaluated the EB rates, the influence of mother's educational level and employment status on EB. Breastfeeding rates in STC were higher compared to conventional counselling (P < 0.01); resuming work was not an EB discouraging variable as 74.5% women in the STC resumed work vs. 54.2% of the conventional counselling. Breastfeeding promotion should start during pregnancy, advising women about benefits for the child in receiving human milk. STC should be used to improve EB in primiparous women.

Should obesogenic- effect be replaced with adipose tissue related alterations in childhood?

During the last year, primary prevention programs for childhood obesity have not obtained the goal in decreasing the prevalence of obesity in pediatric population. This phenomenon remains a crucial issue for the future translating itself in major health problems for the next young-adult generation. However ectopic adipose tissue distribution shows the same obesogenic effect also in slim people. Therefore, the use of adequate language is essential to develop consciousness of overall healthy lifestyle throughout the population. We therefore propone to replace "obesogenic effect" with adipose tissue related alterations also in childhood population.

Metabolic Changes across Tertiles of Delta Changes in Height SDS during Growth Hormone Therapy in Children with Growth Hormone Deficiency.

INTRODUCTION: Obesity, dyslipidemia, hypertension, and insulin resistance are components of the metabolic syndrome and in adults are positively affected by growth hormone (GH) treatment. Few data are available on youth, especially evaluating the improvement of metabolic features after starting GH treatment. The aim of this study was to evaluate changes in metabolic profile in GHD children across tertiles of h-SDS changes after at least 20 months of GH therapy. METHODS: Data from 51 normal-weight children and adolescents with GHD (age: 11.4 ± 2.3 years; h-SDS: -2.25 ± -1.94) who had performed a complete metabolic profile including IGF-1, lipid profile (total cholesterol, triglycerides, HDL cholesterol), glucose metabolism (fasting glycemia, insulin, hemoglobin A1c levels), and insulin resistance indices (HOMA, TG/HDL ratio) before and after start GH treatment were analyzed. Subjects who had received GH therapy for at least 20 months were eligible. Delta changes were calculated for each variable. Subjects were divided according to tertiles of delta changes of h-SDS (1st tertile, 2nd tertile, 3rd tertile) before and after a period of GH treatment. RESULTS: In each tertile group, a significant increase in height SDS was documented. Delta changes in glucose metabolism, lipid profile, and insulin resistance indices significantly improved across tertiles groups, showing the highest tertile a better metabolic pattern. DISCUSSION/CONCLUSIONS: GH therapy is associated with improvement of metabolic profile. Delta changes seem to be more evident in those children with a higher tertile of delta h-SDS after starting GH therapy. A tailored therapy aimed to reach a proper goal in h-SDS after GH treatment might be necessary in order to reduce cardiovascular risk in GHD children.

Early Insulin Resistance, Type 2 Diabetes, and Treatment Options in Childhood.

BACKGROUND: Type 2 diabetes (T2D) represents just the tip of the iceberg of the complex metabolic alterations associated with obesity and other clinical conditions associated to impaired adipose tissue storage. SUMMARY: Available data have suggested the presence of a continuous spectrum of metabolic alterations developed in the progression from insulin resistance (IR) to T2D, most of which are likely preventable through the early characterization of all the multiple risk factors involved. Therefore, the complete characterization of the natural history of the disease and the major modifiable factors represents a milestone in the daily care of young subject at risk for the development of impaired glucose metabolism early in life. This review will focus on the main components defining the risk of IR and T2D in childhood with a specific focus on the main aspects of treatment options available in children and adolescents. KEY MESSAGES: Impaired adipose tissue storage documented in obesity results in a continuous spectrum of metabolic alterations ranging from IR to T2DM. These metabolic alterations are mostly likely preventable through the early characterization of all the multiple risk factors involved. The complete characterization of the disease and of the major modifiable factors represent a milestone in the daily care of young subject at risk for the development of impaired glucose metabolism early in life.