Issues in Diagnosis and Treatment of Type 1 Diabetes Mellitus in Childhood

Type 1 Diabetes Mellitus remains one of the most complex chronic diseases in childhood. Although advances in knowledge and technology, as the use of insulin pumps or glucose sensors, have improved the quality of life of patients, the onset of the disease, as well as long-term treatment and diet, are pitfalls for families and clinicians. It is important to bear in mind that acute, life-threatening consequences of uncontrolled diabetes are hyperglycemia with ketoacidosis, both in new diagnosis and in patients already on treatment, and may be hidden by other symptoms. Moreover, treatment with insulin and diet should always be tailored on lifestyle habits and age of the patient. Aim of this work is to briefly summarise and comment what are the worst insidious aspects of Diabetes and what are the best strategies to improve the management of the disease in childhood

The measurement of urinary gonadotropins for assessment and management of pubertal disorder

OBJECTIVE: Measurement of urinary LH (uLH) and FSH (uFSH) may facilitate non-invasive pubertal assessment but there is a need for further validation by studying children and adolescents with disorders of puberty. DESIGN: 65 cases (Male: 25) with a median age of 12 years (2.9-18.1) supplied at least one non-timed urine sample for uLH and uFSH measurement by immunoassay and corrected for creatinine excretion. 25 cases were receiving GnRH-agonist (GnRH-a) at the time of sample collection. In 41 cases, urine samples were collected prior to a LH RH test and in 12 cases matched serum samples for basal LH (sLH) and FSH (sFSH) were also available. RESULTS: There was a significant correlation between sLH and uLH: uCr (r=0.82; p-value <0.001) and sFSH and uFSH: uCr (r=0.93; p-value <0.001). Based on receiver operator characteristics analysis, a uLH : uCr value of 0.05 IU/mmol as a cut-off would detect a LH peak >5U I/L with a sensitivity of 86% and a specificity of 72% with a positive predictive value of 93%. In pubertal boys (6) and girls (22) with a sLH peak >5UI/L, median uLH: uCr was 0.27 IU/mmol (0.27-0.28) and 0.17 IU/mmol (0.09-0.43), respectively. The median uFSH: uCr was 0.51 IU/mmol (0.41-0.60) for boys and 1.1 IU/mmol (0.21-2.44) for girls. In the 25 cases on GnRH-a, the median uLH : uCr for boys and girls was 0.02 IU/mmol (0.01-0.02) and 0.02 IU/mmol (0.004-0.07), respectively, and the median uFSH: uCr was 0.07 IU/mmol (0.05-0.09) and 0.27 IU/mmol (0.09-0.54), respectively. CONCLUSION: Urinary gonadotrophins reflect serum gonadotrophin concentration and may represent a reliable non-invasive method of assessing pubertal progress

Central precocious puberty in a 3 year-old girl with Phenylketonuria: a rare association?

Background Central precocious puberty (CPP) and phenylketonuria (PKU) are two rare conditions, the latter being the rarer. To date, only one case featuring both these conditions has been reported, and hyperphenylalaninemia was assumed triggering CPP. Case presentation We present a 3.2 years old girl referred with a 12 months history of breast and pubic hair development, and vaginal discharge. Hyperphenylalaninemia had been identified by newborn screening and PKU subsequently confirmed by plasma amino acid and genetic analysis. Early dietary control of plasma phenylalanine had been excellent afterwards, resulting in phenylalanine concentrations consistently within the recommended range. Clinical scenario, hormonal assessment and imaging were in keeping with true idiopathic central precocious puberty. Treatment with long lasting gonadotropin-releasing hormone analogue led to regression of secondary sexual characteristics. Conclusion We describe for the first time CPP in a girl affected with PKU but with persistently well controlled blood phenylalanine concentrations. This finding is in contrast to a previous report which suggested persistently high phenylalaninemia levels as potential trigger for CPP in PKU patients. Our report, together with the lack of evidence in published cohort studies of children with PKU, strongly suggests this rare association is coincidental and independent of the presence of severe hyperphenylalaninemia.</p

Childhood obesity and environmental pollutants: a dual relationship

The rise in obesity rates is an alarming global health concern. Despite obesity is mainly due to an unbalanced energy intake and expenditure, several recent studies suggest that it could be a consequence of exposure during critical developmental windows to environmental chemicals disrupting endocrine functions. This suggests that a shift is occurring in the human body pathways used to integrate changing nutritional and environmental variables and to maintain metabolic balance and body weight. This review highlights the role of pesticides, in particular endocrine disrupter ones, on obesity pathogenesis in childhood and summarizes the current under-standing of the major environmental influences on pediatric obesity. (www.actabiomedica.it)

Challenges in the development and growth of small for gestational age newborns

Introduction: Being born with low birth weight (less than 2.500 gr) is considered a public health problem, with an overall world rate of about 14%. Low birth weight may result from a premature birth (< 37 weeks of gestation), from several causes of intra-uterine growth restriction or from a combination of both. Areas covered: We described how, if weight and/or length at birth are not adequate for gestational age, the newborn is considered ‘small for gestational age’ and may present several growth, hormonal and developmental peculiarities, possibly due to the growth restriction developed during pregnancy. Expert commentary: We provide a description of the possible mid-term consequences of being born small for gestational age and how to follow and provide care for these babies from a multidisciplinary point of view

Cell therapies for pancreatic beta-cell replenishment.

The current treatment approach for type 1 diabetes is based on daily insulin injections, combined with blood glucose monitoring. However, administration of exogenous insulin fails to mimic the physiological activity of the islet, therefore diabetes often progresses with the development of serious complications such as kidney failure, retinopathy and vascular disease. Whole pancreas transplantation is associated with risks of major invasive surgery along with side effects of immunosuppressive therapy to avoid organ rejection. Replacement of pancreatic beta-cells would represent an ideal treatment that could overcome the above mentioned therapeutic hurdles. In this context, transplantation of islets of Langerhans is considered a less invasive procedure although long-term outcomes showed that only 10 % of the patients remained insulin independent five years after the transplant. Moreover, due to shortage of organs and the inability of islet to be expanded ex vivo, this therapy can be offered to a very limited number of patients. Over the past decade, cellular therapies have emerged as the new frontier of treatment of several diseases. Furthermore the advent of stem cells as renewable source of cell-substitutes to replenish the beta cell population, has blurred the hype on islet transplantation. Breakthrough cellular approaches aim to generate stem-cell-derived insulin producing cells, which could make diabetes cellular therapy available to millions. However, to date, stem cell therapy for diabetes is still in its early experimental stages. This review describes the most reliable sources of stem cells that have been developed to produce insulin and their most relevant experimental applications for the cure of diabetes

The "perfect" storm: Current evidence on pediatric inflammatory multisystem disease during SARS-CoV-2 pandemic

Current data suggest that during the global pandemic of COVID 19 children are less affected than adults and most of them are asymptomatic or with mild symptoms. However, recently, cases of pediatric patients who have developed severe inflammatory syndrome temporally related to SARS-CoV-2 have been reported both in USA and Europe. These reports, although sharing features with other pediatric syndromes such as Kawasaki disease (KD), Kawasaki disease shock syndrome (KDSS), macrophage activated syndrome (MAS) and shock toxic syndrome (TSS), seem to outline a novel entity syndrome, characterized by cytokine storm with elevated inflammatory markers and typical clinical finding. Clinical characteristics are greater median age than KD, higher frequency of cardiac involvement and gastrointestinal symptoms, lower frequency of coronary anomalies. We report a summary of the current evidence about clinical features, pathogenesis, therapy strategies and outcome of this novel syndrome

COVID-19 and Type 1 Diabetes: Concerns and Challenges

Due to the current COVID-19 pandemic, worldwide population's lifestyle has changed dramatically, causing psychosocialconsequences. Patients presenting a preexisting chronic condition, as Type 1 Diabetes (T1D), are the ones suffering the most from this situation. Moreover, people affected by diabetes are the ones with the worst prognosis, if infected by SARS-CoV-2. We analyzed why patients with T1D were poorly represented between the subjects hospitalized for COVID-19 and why the cases of diabetic ketoacidosis (DKA) were fewerand more severe compared with the past years. Furthermore, literature has showed howpatients of all ages with T1D did not experience a deterioration in their glucose control throughout the lockdown. Among other causes, this is also due tothe surging use of telemedicine. Finally, we tried to understand how the coronavirus tropism for endocrine tissues could influence the future epidemiology of T1D, focusing on the effects they have on pancreatic beta-cells

Effetti degli interferenti endocrini su crescita e sviluppo puberale

Endocrine disruptors are chemicals present in many areas and materials of the common life, from plastics to detergents, from the air we breathe to the food we eat. Their effect on human health is now known and irrefutable. In fact, several epidemiological studies have identified how endocrine disruptors can act on pre- and postnatal growth, thyroid function, glucose metabolism and obesity, puberty, fertility and carcinogenesis, mainly through epigenetic action mechanisms. The activity of endocrine disruptors occurs mainly during the so-called “window periods”:phases of the child’s life particularly susceptible to epigenetic changes, due to the speed of the accretive processes. Among these periods certainly pre- and postnatal life and the period of puberty stand out, strongly influenced from the point of view of DNA methylation processes

The impact of BMI on long-term anthropometric and metabolic outcomes in girls with idiopathic central precocious puberty treated with GnRHas

BackgroundGonadotropin-releasing hormone analogs (GnRHas) are effective in increasing the final height of children with idiopathic central precocious puberty (ICPP). However, in previous years, some transient metabolic complications have been described during this treatment, for which there are no long-term outcome data. Our study aimed to evaluate the efficacy of GnRHas and clarify if body mass index (BMI) at diagnosis of ICPP could influence long-term outcomes. MethodsThis was an observational, retrospective study that recruited a cohort of girls with ICPP. Data for anthropometric measures, fasting lipid profile, and glucose metabolism were collected at baseline [when GnRHas treatment started (T1)], at the end of the treatment (T2), and near-final height (nFH) or final height (FH) (T3). Predicted adult height (PAH) was calculated at T1 following Bayley and Pinneau's method. Analysis was carried out using BMI standard deviation score (SDS) categories at T1 (group A, normal weight, vs. group B, overweight/obese). ResultsFifty-seven girls with ICPP who were treated with GnRHas were enrolled in the study (group A vs. group B: 33 vs. 24 patients, aged 7.86 +/- 0.81 vs. 7.06 +/- 1.61 years, respectively; p &lt; 0.05). In the study population, nFH/FH was in line with the target height (TH) (p = 0.54), with a mean absolute height gain of 11.82 +/- 5.35 cm compared with PAH. Even if the length of therapy was shorter (group A vs. group B: 1.84 +/- 2.15 vs. 2.10 +/- 0.81 years, respectively; p &lt; 0.05) and the age at menarche was younger (group A vs. group B: 10.56 +/- 1.01 vs. 11.44 +/- 0.85 years, respectively; p &lt; 0.05) in group B than in group A, the nFH/FH gain was still comparable between the two groups (p = 0.95). At nFH/FH, BMI SDS was still greater in group B than in group A (p = 0.012), despite the fact that BMI SDS significantly increased in group A only (p &lt; 0.05). Glucose metabolism got worst during GnRHa with a complete restoring after it, independently from pre-treatment BMI. The ratio of low-density to high-density lipoprotein cholesterol transiently deteriorated during treatment with GnRHas in group A only (p = 0.030). ConclusionsOur results confirm the effectiveness of treatment with GnRHas on growth and do not support the concern that being overweight and obese can impair the long-term outcomes of GnRHas therapy. However, the observed transient impairment of metabolic parameters during treatment suggests that clinicians should encourage ICPP girls treated with GnRHas to have a healthy lifestyle, regardless of their pretreatment BMI