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.

A new formula for premature infants: effects on growth and nutritional status.

OBJECTIVE: Nutritional management influences immediate survival as well as subsequent growth and development of low birth weight and very low birth weight infants. Preterm infant formula (PTF) is used when there is an inadequate supply of mother's milk or when the mother is unable to breastfeed and donor breast milk is unavailable. The purpose of this prospective multicenter study was to evaluate short-term effects on nutritional status (auxological and biochemical parameters) in a population of premature infants who received a preterm infant formula. METHODS: Ninety-seven preterm infants with a birth weight between 500 g and 2000 g and a gestational age of 25-34 weeks postmenstrual age were randomly assigned to received a new preterm infant formula (Nutribèn Pre), and their nutritional status were compared to 75 fortified human milk (FHM) fed infants. RESULTS: No significant differences were observed between FHM and Nutribèn Pre fed infants in terms of growth, feeding tolerance and biochemical profiles. CONCLUSION: Nutribèn Pre is a valid, effective and safe alternative for the nutrition of preterm infants.

Mode of delivery affects the bacterial community in the newborn gut.

The first colonisation of the intestine is one of the most profound immunological exposures faced by the newborn and it is influenced by external and internal factors. The early composition of human microbiota could have long-lasting metabolic effects and the initial composition of human intestinal bacteria is also known to affect postnatal immune system development, as we are already aware that reduced microbial stimulation during infancy would result in slower postnatal maturation of the immune system and development of an optimal balance between TH1 and TH2-like immunity. Mode of delivery has a major role on the composition of intestinal microbiota in early infancy, as it has been shown that infants born by Caesarean section (CS) have lower numbers of Bifidobacteria and Bacteroides compared with vaginally born infants. We designed a study to investigate the influence of mode of delivery (CS vs. vaginal delivery) on intestinal microbial composition on day 3 of life using PCR-denaturing gradient gel electrophoresis (DGGE) and PCR-temperature gradient gel electrophoresis (TGGE). Both DGGE and TGGE analyses have been used, together with the specific amplifications for 10 Bifidobacterium sp., 3 Ruminococcus sp., and Bacteroides that all have a highly relevant physiological role in the intestinal ecosystem of the newborn. A total of 46 term infants were enrolled in the study, consecutively recruiting all the CS-delivered babies (n=23; 8 males and 15 females) and the immediately following spontaneously delivered babies (n=23; 11 males and 12 females). DGGE analysis carried out with Bifidobacterium-specific primers revealed the presence of this genus in 13 of 23 (56.5%) samples derived from vaginally delivered newborns but in none of the samples obtained from newborns delivered by CS. PCR analysis with Bifidobacterium-species-specific primers showed that naturally delivered infants had a large number of bifidobacterial species, whereas in CS-delivered babies only two samples (8.7%) gave positive results, one for B. longum and another for B. gallicum. In all babies enrolled, micro-organisms belonging to Ruminococcus species were absent and Bacteroides was found in 8.7% of spontaneously delivered babies only. Based on our findings, it seems that newborn's intestinal bacteria during the first 3days of life are strongly influenced by mode of delivery. The intestinal flora of CS and vaginally delivered infants appears to be very different; the former being altered and characterised by a substantial absence of Bifidobacteria sp., the latter characterised by subject-specific microbial profiles, although predominant groups such as B. longum and B. catenulatum could be identified. In summary, mode of delivery does affect the early stage of intestinal bacterial colonisation, which is altered in CS-delivered infants compared with vaginally delivered infants, with only a minor influence of the type of feeding. In addition, the importance of methodological aspects for determining intestinal microbiota in clinical trials requires emphasis if intestinal microbiota composition is to be considered a measure of postnatal adaptation.

Early progression of the autonomic dysfunction observed in pediatric type 1 diabetes mellitus.

To focus on early cardiac and vascular autonomic dysfunction that might complicate type 1 diabetes mellitus in children, we planned an observational, cross-sectional study in a population of 93 young patients, under insulin treatment, subdivided in 2 age subgroups (children: 11.5+/-0.4 years; adolescents: 19.3+/-0.2 years). Time and frequency domain analysis of RR interval and systolic arterial pressure variability provided quantitative indices of the sympatho-vagal balance regulating the heart period, of the gain of cardiac baroreflex, and of the sympathetic vasomotor control. Sixty-eight children of comparable age served as a reference group. At rest, systolic arterial pressure and the power of its low-frequency component were greater in patients than in controls, particularly in children (14.0+/-2.3 versus 3.1+/-0.3 mm Hg2). Moreover, baroreflex gain was significantly reduced in both subgroups of patients. Standing induced similar changes in the autonomic profiles of controls and patients. A repeat study after 1 year showed a progression in low-frequency oscillations of arterial pressure and a shift toward low frequency in RR variability. Data in young patients with type 1 diabetes mellitus show a significant increase in arterial pressure, a reduced gain of the baroreflex regulation of the heart period, and an increase of the low-frequency component of systolic arterial pressure variability, suggestive of simultaneous impairment of vagal cardiac control and increases of sympathetic vasomotor regulation. A repeat study after 1 year shows a further increase of sympathetic cardiac and vascular modulation, suggesting early progression of the autonomic dysfunction.

Long-lasting immunogenicity of a virosomal vaccine in older children and young adults with type I diabetes mellitus.

To evaluate the long-lasting immunogenicity and reactogenicity of a virosomal influenza vaccine in subjects with type I diabetes, a trial was conducted during the 2007-2008 influenza season in Milan, Northern Italy. One hundred five subjects aged 9-30 years were randomized to receive by intramuscular injection vaccination by a single dose (0.5 ml) of either a virosomal (Inflexal V) (n=52) or a standard subunit (Influvac) (n=53) vaccine. Serum hemagglutinin inhibition antibody titres were determined against the three recommended influenza-like strains, A/H1N1, A/H3N2 and B, at pre-vaccination, and 1 and 6 months post-vaccination. Geometric mean titres were increased in the two groups 1 and 6 months post-vaccination (P<0.001). One month post-vaccination both vaccines met the CPMP requirement for immunogenicity with high seroprotection rates (>95%) for strains A/H1N1 and A/H3N2, and a seroprotection of 73% and 70% in the virosomal and subunit vaccine for strain B. Mean fold increase ranged 2.8 (A/H3N2)-6.2 (A/H1N1) in the virosomal group and 2.3 (A/H3N2)-4.8 (A/H1N1) in the subunit group. Immunogenicity declined 6 months post-vaccination in both groups, and the CPMP requirement for immunogenicity was satisfied only in the virosomal group. In subjects without pre-existing antibodies to strain B (titre <10), the virosomal vaccine showed higher immune response than the subunit vaccine 6 months post-vaccination, with a geometric mean titre (95% CI) of 40.2 (30.7-54.6) vs. 21.2 (14.6-30.8). Reactogenicity was similar in the two vaccines. All reactions were transient and not severe. The results indicate that in older children and young adults with type I diabetes influenza vaccination with a virosomal or a standard subunit vaccine is safe and adequately immunogenic against the three influenza vaccine strains. In addition, the virosomal vaccine may show better long-lasting immune response than the standard subunit vaccine, especially in subjects without pre-existing antibodies to influenza strains.

Insulin pump therapy for type 1 diabetes treatment in a girl with Down's syndrome.

We present the case of a 29.5-year-old girl with Down's syndrome, type 1 diabetes mellitus (DMT1), autoimmune thyroiditis and celiac disease starting on insulin pump therapy. After 22-month follow-up hemoglobin A1c dropped from 9% to 6.8%, even with a lower insulin requirement and no change in BMI.

Thyroid dysfunction in antiretroviral treated children.

BACKGROUND: A high rate of thyroid disorders has been described in HIV-infected adults treated with highly active antiretroviral therapy (HAART), but data on children are lacking. We aimed to assess thyroid function in pediatric patients. METHODS: Fifty-two HIV-infected children receiving HAART were assessed for signs of thyroid dysfunction and serum concentrations of thyrotropin (TSH), free thyroxin (FT4), free triiodothyronine (FT3), thyroglobulin (TG), reverse triiodothyronine (rT3), anti-TG and antimicrosomal (anti-TSM) antibodies. RESULTS: Eighteen (35%) children showed thyroid abnormalities: isolated low FT4 value in 16; subclinical hypothyroidism in 1; and symptomatic hypothyroidism in 1. Children with low FT4 values as compared with the 34 children without thyroid dysfunction were similar for stage of disease, number of patients with undetectable HIV-RNA, FT3, TSH, TG, rT3, anti-TSM and anti-TG values, whereas they had shorter duration of HAART exposure (P = 0.019) and lower CD4 cell percentage (P = 0.035). The thyrotropin-releasing hormone (TRH) test was normal in all children with low FT4 values. Among children with low FT4, FT4 concentrations correlated positively with CD4 cell percentage (P < 0.05) and duration of HAART exposure (P < 0.05). The case with subclinical hypothyroidism had high basal TSH (7.3 microunits/ml), normal TSH response to TRH test and normal FT4, FT3, TG, rT3, anti-TG and anti-TSM antibodies. The case with symptomatic hypothyroidism had low FT4 (6.6 pg/ml) and high TSH (44 microunits/ml), TG (55 ng/ml), anti-TG (666 IU/ml) and anti-TSM (123 IU/ml). CONCLUSION: Thyroid abnormalities occur frequently in HAART-treated children even in the absence of clinical symptoms. These data suggest a need of regular thyroid function monitoring.

Expansion of specific alphabeta+ T-cell subsets in the myocardium of patients with myocarditis and idiopathic dilated cardiomyopathy associated with Coxsackievirus B infection.

Idiopathic dilated cardiomyopathy (IDC) is one of the major causes of death in humans and has been linked to Coxsackievirus B (CVB) infection. The aim of this study was to analyze phenotypes of heart-infiltrating immune cells in patients suffering from myocarditis and IDC associated with CVB infections. We found that the myocardium of these patients was infiltrated by CD4(+) and CD8(+) T lymphocytes as well as macrophages. Evidence of CVB3/4 infections was also found. In the majority of patients, the T-cell receptor repertoire (TCR) of the infiltrating lymphocytes was restricted, with a polyclonal expansion of the Vbeta7 gene family. We also found that human leukocyte antigen (HLA) class II alleles associated with susceptibility to type 1 diabetes (HLA-DR4 and HLA-DQA1*04/05/06 alleles) were remarkably infrequent in IDC patients (p < 0.005), thus suggesting that they might confer protection against IDC. Finally, mRNA for interleukin-1beta, interferon-gamma, and tumor necrosis factor-alpha was detected in the cardiac specimens, although at a lower level compared with specimens from hearts without signs of viral infections. We conclude that CVB infection of the human myocardium is associated with a selective, yet polyclonal activation of different T-cell subsets in genetically susceptible individuals. This immune response may play a critical role in modulating disease progression after viral infections.