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

Obesity and craniopharyngioma.

An epidemic of pediatric obesity has occurred across the world in recent years. There are subgroups within the population at high-risk of becoming obese and especially of having experience of precocious cardiovascular and metabolic co-morbidities of obesity. One of these subgroups comprises patients treated for childhood cancers and namely survivors of craniopharyngioma. The high incidence of obesity in this group makes these patients an important disease model to better understand the metabolic disturbances and the mechanisms of weight gain among cancer survivors. The hypothalamic-pituitary axis damage secondary to cancer therapies or to primary tumor location affect long-term outcomes. Nevertheless, the aetiology of obesity in craniopharyngioma is not yet fully understood. The present review has the aim of summarizing the published data and examining the most accepted mechanisms and main predisposing factors related to weight gain in this particular population

Effects of Exercise in Children and Adolescent with Type 1 Diabetes Mellitus

Exercise is one of the most important components, together with insulin therapy and diet, in the clinical management of type 1 diabetes mellitus (T1DM). Physical activity has multiple health benefits, like blood pressure reduction, improvement of cardiovascular fitness and lipoprotein profile. The benefits for children with diabetes may also include positive effects on glycemic metabolism. The following review examines the main studies about the effects of exercise on diabetes. Additional longitudinal studies are needed to verify the hypothetical positive relationship between sport and T1DM and between sport and diabetic complications. However, aerobic and moderate intensity physical activity in children and adolescents with T1DM should be encouraged also for its beneficial psychological effects

Effect of Weight Loss on Markers of Inflammation and Endothelial Function in Childhood Obesity

Background: Obesity is associated with chronic low-grade inflammation and hyperinsulinism that may influence the progression of endothelial dysfunction and atherosclerosis already in childhood. Methods: To study changes in metabolic profile and markers of inflammation and endothelial activation in children with primary severe obesity after weight loss we involved 14 obese children (Ob) that underwent a lifestyle intervention and 18 normal weighted subjects (C). In Ob, anthropometric data were assessed both at baseline and after intervention together with oral glucose tolerance test and fasting evaluation of cholesterol assessment, interleukin-6, endogenous secretory receptor of advanced glycation end products and endothelin levels. Results: At baseline, serum IL-6 concentrations resulted significantly higher in Ob respect to C (12.96 ± 8.87 vs.4.88 ± 1.19 pg/ml, p<0.05). After weight loss, Ob significantly improved glucose metabolism and lipid assessment and they showed a significant reduction of all markers of inflammation and endothelial activation. In all subjects studied, BMI-SDS correlated positively with interleukin-6 (r 0.45, p<0.05). Conclusion: Our results demonstrated higher concentrations of inflammatory markers in obese children compared to healthy subjects. Nevertheless, an early lifestyle intervention could improve the levels of these molecules together with cholesterol and glucose metabolism and may reverse the development of premature endothelial dysfunction in obese children

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)

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

Unusual osseous presentation of blastomycosis in an immigrant child: a challenge for European pediatricians.

Blastomycosis, caused by the thermally dimorphic fungus Blastomyces dermatitidis is a systemic pyogranulomatous infection, endemic in United States and Canada, with few reported cases in Africa and Asia. It is uncommon among children and adolescents, ranging from 3% to 10%. Clinical features vary from asymptomatic spontaneously healing pneumonia, through acute or chronic pneumonia, to a malignant appearing lung mass. Blastomycosis can originate a "metastatic disease" in the skin, bones, genitourinary tract and central nervous system. Bone is the third most common site of blastomycotic lesions, after lung and skin. Bones may be involved in 14-60% of cases of blastomycosis. Direct visualization of single broadbased budding yeast with specific stains in sputum or tissue samples at microscopy is the primary method for diagnosis, while culture is timeconsuming and other methods are unreliable. CASE PRESENTATION: We report a case of severe osteoarticular Blastomycosis occurring in a 3-years-old presented to our Emergency Department with pain and swelling of the left knee, successfully treated with surgical curettage and antifungal therapy. To our knowledge this is the first case reported in Europe. CONCLUSIONS: Blastomycosis represents a challenge for European physicians, and it should be included in the differential diagnosis of unexplained infections in patients coming from endemic areas

Glycemic Control in Kenyan Children and Adolescents with Type 1 Diabetes Mellitus

Background. Type 1 diabetes mellitus (T1DM) is the most common endocrine disorder in children and adolescents worldwide. While data about prevalence, treatment, and complications are recorded in many countries, few data exist for Sub-Saharan Africa. The aim of this study was to determine the degree of control in patients with T1DM aged 1\u201319 years over a 6-month period in 3 outpatient Kenyan clinics. It also sought to determine how control was influenced by parameters of patient and treatment. Methods. Eighty-two children and adolescents with T1DM were included in the study. Clinical history regarding duration of illness, type and dose of insulin, and recent symptoms of hypoglycemia/hyperglycemiawere recorded. Glycaemia, HbA1c, and ketonuria were tested. HbA1c of 8.0% and below was defined as the cut-off for acceptable control. Results. The median HbA1c for the study population was 11.1% (range: 6.3\u201318.8). Overall, only 28% of patients had reasonable glycemic control as defined in this study. 72% therefore had poor control. It was also found that age above 12 years was significantly associated with poor control. Conclusions. African children and with T1DM are poorly controlled particularly in adolescents. Our data strongly support the necessity of Kenya children to receive more aggressive management and follow-up

In vitro differentiation of human amniotic epithelial cells into insulin-producing 3D spheroids

Regenerative medicine and stem cell therapy may represent the solution for the treatment of non-curable human diseases such as type 1 diabetes. In this context of growing demand for functional and safe stem cells, human amniotic epithelial cells (hAECs) from term placenta have attracted increasing interest for their wide availability, stem cell properties, and differentiation plasticity, which make them a promising tool for stem cell-based therapeutic applications. We initially assayed the stemness characteristics of hAECs in serum-free conditions. Subsequently we developed a culture procedure on extracellular matrix for the formation of three-dimensional (3D) spheroids. Finally, we tested the immunomodulation and differentiation potential of hAEC spheroids: the presence of pancreatic endocrine hormones was revealed with transmission electron microscopy and immunofluorescence analyses; the release of C-peptide in hyperglycemic conditions was assayed with ELISA.The serum-free culture conditions we applied proved to maintain the basic stemness characteristics of hAECs. We also demonstrated that 3D spheroids formed by hAECs in extracellular matrix can be induced to differentiate into insulin-producing cells. Finally, we proved that control and induced cells equally inhibit the proliferation of activated mononuclear cells.The results of this study highlight the properties of amnion derived epithelial cells as promising and abundant source for cell-based therapies. In particular we are the first group to show the in vitro pancreatic induction of hAECs cultured on extracellular matrix in a 3D fashion. We accordingly propose the outcomes of this study as a novel contribution to the development of future cell replacement therapies involving placenta-derived cells

Unusual presentation of Rosai-Dorfman disease in a 14-month-old Italian child: a case report and review of the literature

Background: Rosai-Dorfman disease (RDD) is a rare form of histiocytosis characterized by histiocyte proliferation within lymph nodes and extranodal tissue. Here we report an unusual presentation of RDD in an Italian toddler. Moreover, we reviewed the pediatric case reports published between 2004 and 2014, focusing in particular on medical therapy. Case presentation: We report the case of a 14-month-old child who developed a progressive swelling of the right parotid, associated with systemic symptoms and abnormal blood tests. During diagnostic work-up, cervical, intraparotid, and unilateral hilar lymphadenopathies were found. Histopathological and immunohistochemistry studies of a cervical lymph node biopsy established the diagnosis of RDD, with positive PCR for Epstein - Barr virus on the biopsy specimen. Oral steroid therapy was started with progressive reduction in size of all lesions, resolution of systemic symptoms, and normalization of blood tests. Conclusion: RDD is generally considered a benign and self-limiting form of histiocytosis, usually associated with favorable prognosis. However, complications are not infrequent and fatal cases were reported even in children. Efforts should be made to establish the best therapeutic strategy for this disease, as no well-defined guidelines exist. Finally, RDD should be included in differential diagnosis of lymphadenopathy and parotid swelling even in very young children