Type 1 Diabetes at-risk children highly recognize <i>Mycobacterium avium</i> subspecies <i>paratuberculosis</i> epitopes homologous to human Znt8 and Proinsulin

Mycobacterium avium subspecies paratuberculosis (MAP) has been previously associated to T1D as a putative environmental agent triggering or accelerating the disease in Sardinian and Italian populations. Our aim was to investigate the role of MAP in T1D development by evaluating levels of antibodies directed against MAP epitopes and their human homologs corresponding to ZnT8 and proinsulin (PI) in 54 T1D at-risk children from mainland Italy and 42 healthy controls (HCs). A higher prevalence was detected for MAP/ZnT8 pairs (62,96% T1D vs. 7,14% HCs; p &lt; 0.0001) compared to MAP/PI epitopes (22,22% T1D vs. 9,52% HCs) and decreasing trends were observed upon time-point analyses for most peptides. Similarly, classical ZnT8 Abs and GADA decreased in a time-dependent manner, whereas IAA titers increased by 12%. Responses in 0–9 year-old children were stronger than in 10–18 age group (75% vs. 69,1%; p &lt; 0.04). Younger age, female sex and concomitant autoimmune disorders contributed to a stronger seroreactivity suggesting a possible implication of MAP in multiple autoimmune syndrome. Cross-reactivity of the homologous epitopes was reflected by a high correlation coefficient (r2 &gt; 0.8) and a pairwise overlap of positivity (&gt;83% for MAP/ZnT8)

Estimated insulin sensitivity, cardiovascular risk, and hepatic steatosis after 12 years from the onset of T1D

Aim To test the hypothesis that intensive insulin treatment and optimal glycaemic control are not fully protective against reduction of insulin sensitivity in children with type 1 diabetes.Material and methods Cohort study of 78 normal-weight patients with prepubertal onset (T (0)) and follow-up waves at 1 (T (1)), 5 (T (5)), 10 (T (10)), and 12 (T (12)) years; matched for age and sex to 30 controls at T (12). Estimated insulin sensitivity (eIS) by three formulae; ultrasound evaluation of para and perirenal fat thickness; hepatic steatosis (HS); carotid intima media thickness (cIMT) at T (12).Results At T12, the 36 patients (46%) who had constantly or prevalently haemoglobin A1c (HbA1c) &lt; 58 mmol/l during follow-up showed better eIS indexes (p = 0.049 to &lt;0.0001); lipid profile (p = 0.042 to &lt;0.0001), reduced fat mass (p = 0.012) and required lower insulin dose (p = 0.032) than the 42 patients (54%) with HbA1c &gt;= 58 at T12. Patients (N = 25) with eIS(EDC) &lt; 8.77 mg kg(-1) min(-1) showed higher cIMT (p &lt; 0.0001). HS was found in 6 patients (similar to 8%). In patients and normal-weight controls, fat mass (p = 0.03), age (p = 0.03), cIMT (p = 0.05) predicted HS; eIS indexes (p from 0.04 to &lt;0.0001) predicted cIMT. Body mass index, perirenal fat, fat mass, and triglycerides to high density lipoprotein cholesterol ratio were associated with eIS indexes (p from 0.03 to &lt;0.0001).Conclusions Young T1D patients have reduced insulin sensitivity and higher cIMT. Adiposity, glucose, and lipid control over follow-up are likely to influence both. Enhanced adiposity seems of paramount relevance for the onset of HS in T1D patients alike in healthy youths

Seroreactivity against specific L5P antigen from <i>Mycobacterium avium</i> subsp. <i>paratuberculosis</i> in children at risk for T1D

Aims/Hypothesis: Although numerous environmental agents have been investigated over the years as possible triggers of type 1 diabetes (T1D), its causes remain unclear. We have already demonstrated an increased prevalence of antibodies against peptides derived from Mycobacterium avuim subsp. paratuberculosis (MAP) homologous to human zinc transporter 8 protein (ZnT8) and proinsulin in Italian subjects at risk for or affected by T1D. In this study, we compared titers of the previously detected antibodies with seroreactivity to MAP lipopentapetide (L5P) that recently emerged as a strong immunogenic component able to specifically distinguish MAP from other mycobacteria. Methods: Plasma of 32 children and youth at risk for T1D including follow-up samples and 42 age-matched healthy controls (HC) recruited at the Tor Vergata University Hospital in Rome was analyzed by indirect ELISA for the presence of antibodies against MAP-derived epitopes MAP3865c133–141, MAP3865c125-133, MAP2404c70-85 and MAP1,4αgbp157-173 along with their ZnT8 and proinsulin homologs. The data were analyzed through two-tailed Mann-Whitney U test and relation between variables was determined by principal component analysis. Results: Responses to L5P were not detectable in subjects whose initial seroreactivity to MAP peptides and their human homologs was lost in follow-up samples, whereas anti-L5P antibodies appeared constantly in individuals with a stable immunity against MAP antigens. The overall coincidence in positivity to L5P and the four MAP epitopes both in children at risk for T1D and HC exceeded 90%. Conclusions: MAP-derived homologs may cross-react with ZnT8 and proinsulin peptides inducing immune responses at a young age in subjects predisposed for T1D. Thus, L5P may have a diagnostic value to immediately indicate the presence of anti-MAP seroreactivity when evaluation of a more complex antibody status is not required. Almost complete coincidence in responses to both types of antigens lends support to the involvement of MAP in T1D

Evaluation and prevention of type II diabetes mellitus and cardiovascular diseases in obese children and adolescents: a public health intervention in a local health organisation in Rome (Italy) [Un intervento di sanità pubblica per la valutazione e la prevenzione del diabete di tipo 2 e delle malattie cardiovascolari in bambini e adolescenti obesi.]

INTRODUCTION: Prevention of childhood obesity and of its complications is an increasingly important public health priority. During 2002-2003 a network of family paediatricians working in the territory of a local health organisation in Rome (Italy) was created, in order to evaluate the health status of obese children. A preferential diagnostic and therapeutic management workup procedure was then developed for these patients at the Paediatrics department of the "Policlinico Tor Vergata" (PTV) university teaching hospital in Rome (Italy). METHODS: Family paediatricians invited children aged 6-14 years with a body mass index (BMI) above the 95th percentile, to a clinical consultation at PTV where each child then underwent a clinical evaluation (including blood pressure measurement and evaluation of family history of cardiovascular disease and type 2 diabetes mellitus) and laboratory testing (including oral glucose tolerance testing-OGTT, measurement of cholesterol and trygliceride levels). The BMI z score and insulin resistance index (HOMA-IR) were also calculated and pubertal stage was assessed. RESULTS: Overall, 168 children, with a mean age of 11 years, were evaluated; 53% were males. The mean BMI z score was 2.43+/-0.45. Forty-four percent of children were found to be hypertensive and 28.3% had a positive family history for type 2 diabetes mellitus. Fifteen children (9%) were found to have Impaired Glucose Tolerance (IGT) while one child was frankly diabetic. Thirty-six children (23.4%) were diagnosed with a metabolic syndrome (MS). Systolic blood pressure was significantly correlated with BMI z score and with 2 hour glucose levels. Obese children with either hypertension or a family history of diabetes were significantly more likely to have glucose intolerance or metabolic syndrome (GI, OR= 4.7 ; MS, OR= 6.8) CONCLUSIONS: A high percentage of obese children and adolescents develop metabolic complications. The percentage of children with such complications is greater when other risk factors such as hypertension and family history of type 2 diabetes are present. Family paediatricians play a fundamental role in the prevention, evaluation and treatment of child obesity. This study underscores the importance of performing routine evaluations of BMI and blood pressure in children aged 6-14 years, eventually by extending well-child visits to this age group

[Evaluation and prevention of type II diabetes mellitus and cardiovascular diseases in obese children and adolescents: a public health intervention in a local health organisation in Rome (Italy)]

Prevention of childhood obesity and of its complications is an increasingly important public health priority. During 2002-2003 a network of family paediatricians working in the territory of a local health organisation in Rome (Italy) was created, in order to evaluate the health status of obese children. A preferential diagnostic and therapeutic management workup procedure was then developed for these patients at the Paediatrics department of the "Policlinico Tor Vergata" (PTV) university teaching hospital in Rome (Italy)

Seroreactivity against Specific L5P Antigen from Mycobacterium avium subsp. paratuberculosis in Children at Risk for T1D

Although numerous environmental agents have been investigated over the years as possible triggers of type 1 diabetes (T1D), its causes remain unclear. We have already demonstrated an increased prevalence of antibodies against peptides derived from Mycobacterium avuim subsp. paratuberculosis (MAP) homologous to human zinc transporter 8 protein (ZnT8) and proinsulin in Italian subjects at risk for or affected by T1D. In this study, we compared titers of the previously detected antibodies with seroreactivity to MAP lipopentapetide (L5P) that recently emerged as a strong immunogenic component able to specifically distinguish MAP from other mycobacteria.[br/] Plasma of 32 children and youth at risk for T1D including follow-up samples and 42 age-matched healthy controls (HC) recruited at the Tor Vergata University Hospital in Rome was analyzed by indirect ELISA for the presence of antibodies against MAP-derived epitopes MAP3865c133-141, MAP3865c125-133, MAP2404c70-85 and MAP1,4αgbp157-173 along with their ZnT8 and proinsulin homologs. The data were analyzed through two-tailed Mann-Whitney U test and relation between variables was determined by principal component analysis.[br/] Responses to L5P were not detectable in subjects whose initial seroreactivity to MAP peptides and their human homologs was lost in follow-up samples, whereas anti-L5P antibodies appeared constantly in individuals with a stable immunity against MAP antigens. The overall coincidence in positivity to L5P and the four MAP epitopes both in children at risk for T1D and HC exceeded 90%.[br/] MAP-derived homologs may cross-react with ZnT8 and proinsulin peptides inducing immune responses at a young age in subjects predisposed for T1D. Thus, L5P may have a diagnostic value to immediately indicate the presence of anti-MAP seroreactivity when evaluation of a more complex antibody status is not required. Almost complete coincidence in responses to both types of antigens lends support to the involvement of MAP in T1D