Giovanna Contreas

Diet, physical, and biochemical characteristics of children and adolescents with type 1 diabetes: relationship between dietary fat and glucose control

Maffeis C, Morandi A, Ventura E, Sabbion A, Contreas G, Tomasselli F, Tommasi M, Fasan I, Costantini S, Pinelli L. Diet, physical, and biochemical characteristics of children and adolescents with type 1 diabetes: relationship between dietary fat and glucose control.

Analysis of CIITA encoding AIR-1 gene promoters in insulin-dependent diabetes mellitus and rheumatoid arthritis patients from the Northeast of Italy: Absence of sequence variability

Qualitative and/or quantitative alterations in the expression of the MHC class II molecules affect the onset and maintenance of the immune response and may be the basis of a wide variety of disease states, such as autoimmunity and immunodeficiency.CIITA is a major physiological regulator of the expression of MHC class II genes. The availability of CIITA ap- pears generally essential for MHC class II gene expression, and hence its own transcriptional regulatory mechanisms result of fundamental importance for a correct homeostasis of the immune response. Therefore, it is possible to hypothesize that variability at the CIITA-encoding locus, AIR-1, could constitute an additional source of susceptible traits to autoimmune diseases. Mutations at AIR-1/CIITA promoters could modulate expression of CIITA. Variations in CIITA expression could influence the qualitative and quantitative expression of MHC class II molecules at cell surface. We have analyzed sequence variation at AIR-1/CIITA promoters by PCR-SSCP in 23 IDDM and 30 RA patients compared to a sample of 19 unaffected normal controls and 16 unaffected IDDM family members, for a total of 88 Caucasian subjects from the Northeast of Italy. No sequence difference was found at the four AIR-1/CIITA promoters between autoimmune patients and normal controls. Moreover, the promoters resulted invariant within the entire group of 88 subjects analyzed, comprising patients and controls. This finding suggests a possible selective advantage in maintaining CIITA upstream regulatory sequences invariant.

Association between intestinal permeability and faecal microbiota composition in Italian children with beta cell autoimmunity at risk for type 1 diabetes.

Pancreatic organ‐specific autoimmunity in subjects at risk for type 1 diabetes (T1D) is associated with increased intestinal permeability and an aberrant gut microbiota, but these factors have not yet been simultaneously investigated in the same subjects. Thus, the aim of this study was to assess both intestinal permeability and gut microbiota composition in an Italian sample of children at risk for T1D.

Monogenic Diabetes Accounts for 6.3% of Cases Referred to 15 Italian Pediatric Diabetes Centers During 2007 to 2012

Context An etiologic diagnosis of diabetes can affect the therapeutic strategy and prognosis of chronic complications. Objective The aim of the present study was to establish the relative percentage of different diabetes subtypes in patients attending Italian pediatric diabetes centers and the influence of an etiologic diagnosis on therapy. Design, Setting, and Patients This was a retrospective study. The clinical records of 3781 consecutive patients (age, 0 to 18 years) referred to 15 pediatric diabetes clinics with a diagnosis of diabetes or impaired fasting glucose from January 1, 2007 to December 31, 2012 were examined. The clinical characteristics of the patients at their first referral to the centers, type 1 diabetes-related autoantibodies, molecular genetics records, and C-peptide measurements, if requested for the etiologic diagnosis, were acquired. Main Outcome Measures The primary outcome was to assess the percentage of each diabetes subtype in our sample. Results Type 1 diabetes represented the main cause (92.4%) of diabetes in this group of patients, followed by monogenic diabetes, which accounted for 6.3% of cases [maturity onset diabetes of the young (MODY), 5.5%; neonatal diabetes mellitus, 0.6%, genetic syndromes, 0.2%]. A genetic diagnosis prompted the transfer from insulin to sulphonylureas in 12 patients bearing mutations in the HNF1A or KCNJ11 genes. Type 2 diabetes was diagnosed in 1% of the patients. Conclusions Monogenic diabetes is highly prevalent in patients referred to Italian pediatric diabetes centers. A genetic diagnosis guided the therapeutic decisions, allowed the formulation of a prognosis regarding chronic diabetic complications for a relevant number of patients (i.e.,GCK/MODY), and helped to provide genetic counseling.

Normal or defective immune response to Hepatitis B vaccine in patients with diabetes and celiac disease

A defective production of protective levels of antibodies to Hepatitis B (HB) vaccine is reported to occur in 4–10% of healthy subjects and a correlation with the presence of specific human leukocyte antigen (HLA) molecules, including DQ2, which also confers genetic predisposition to celiac disease (CD) and type I diabetes mellitus (T1DM), has been suggested. The aim of this study was to analyze the serological response to HB vaccine and measles-containing vaccines in 69 diabetic patients (T1DM), 42 patients with celiac disease (CD) and 79 healthy control subjects (CT). The median interval between the third dose of HB vaccine and serum collection was 6.8, 3.5, and 4.7 years for T1DM, CD and CT groups, respectively. 50/69 (72%) T1DM patients, 32/42 (76%) CD patients and 61/79 (77%) CT subjects showed protective anti-HBs antibodies after vaccination, with no statistically significant difference. On the contrary, a lower statistically significant difference was found in the mean HBsAb level of T1DM subjects when compared with the other two groups. No correlation between HLA DQ2 expression in T1DM and vaccine response was detected. The comparison of serological response to measles after vaccination also showed no statistically significant differences in the three groups. Contrasting results between these data and those reported in the literature might be due to differences in the time intervals between vaccination and testing. Prospective studies in pathological and healthy groups with the same age at HBV vaccination and with the same time interval for blood sample collection to determine antibody titers are necessary in order to provide more conclusive data.

Epidemiology of type 1 diabetes mellitus in the pediatric population in Veneto Region, Italy

We assessed the prevalence and incidence of type 1 diabetes mellitus (T1DM) in Veneto Region in Italy. The average prevalence and incidence rates were 1.26/1000 subjects and 16.5/100,000 person-years, respectively. This study shows that the Veneto Region is an area with intermediate-high risk of T1DM.

Anxiety, Depression and Quality of Life in Italian Youths with Type 1 Diabetes Mellitus

Background: Psychological problems and low quality of life (QoL) in children with type 1 Diabetes Mellitus T1DM) were reported as correlated with T1DM. This study wants to test if the prevalence of anxiety and depression is higher in young patients with T1DM than in controls, if the level of QoL is lower and if anxiety and QoL correlate with glyco-metabolic control. Methods: A total of 100 children with T1DM, aged 8-13 years, were recruited and 114 healthy children were recruited as controls. All children with T1DM were receiving a routine psychological support. Patients and controls underwent three questionnaires [the Self Administrated Psychiatric Scale Scales for Children and Adolescents (SAFA), the Children’s Depression Inventory (CDI) and the Pediatric Quality of Life Inventory (PedsQL)]. Diabetes–related, physical and socio-demographic parameters were also collected. Results: SAFA, CDI and PedsQL mean score were not statistically different in T1DM and in control group. Just the “separation anxiety” scale showed significantly higher mean score in the T1DM than in the control group (43.77 ± 10.34 vs. 23.11 ± 18.25, p<0.01). A significant correlation between QoL and metabolic control (HbA1c) (r=0.21, p<0.05) was found. HbA1c increased with the mother’s education (r=0.42, p<0.05) and occupation level (r=0.35, p<0.05), and with the number of siblings (r = 0.20, p<0.05). Conclusions: T1DM is not a condition promoting per se more psychological discomfort even if a higher level of separation anxiety was shown. Interestingly, a higher level of self-perceived QoL was associated with worse glycometabolic control. Significant findings of the study: 1. The anxiety, depression and QoL levels were not significantly different in children with T1DM vs healthy peers even if children with T1DM showed higher separation anxiety 2. There was not association between psychological parameters and the glycometabolic control (HbA1c) What this study adds: The self-perceived QoL, in subjects with T1DM, was higher in subjects with worse glycometabolic control and lower in patients with better glycometabolic control Psycho-educational and therapeutic programs should sustain parents and children with T1DM

A novel synonymous substitution in the GCK gene causes aberrant splicing in an Italian patient with GCK-MODY phenotype

GCK gene analysis in an Italian MODY patient revealed a novel synonymous substitution in exon 4 (c.459T>G; p.Pro153Pro) resulting in an aberrant transcript lacking the last eight codons of the same exon. Our findings emphazise the importance of not underestimating synonymous variations when screening for disease-causing mutations.

Analysis of the yeast NSR1 gene and protein domain comparison between Nsr1 and human hnRNP type A1

The yeast nucleolar protein-encoding gene NSR1 was isolated by low-stringency screening of a yeast genomic library with the human heterogeneous nuclear ribonucleoprotein type A1 (hnRNP A1) cDNA probe, and was mapped to chromosome VII. RNA abundance was determined and the transcription start point and polyadenylation site were mapped. A comparison between the Nsr1 and hnRNP A1 proteins, based on homopolymer RNA binding to their structural domains in vitro, revealed a striking biochemical similarity. When the N-terminal, lysine- and arginine-rich domain of Nsr1 was removed, the truncated protein behaved similarly to hnRNP A1; furthermore, the two RRM (RNA recognition motif) domains of Nsr1 behaved in the same manner as the two RRM domains of hnRNP A1. The biochemical data, therefore, would support the hypothesis that the two RRM domains in hnRNP A1 and Nsr1 interact with RNA in a similar manner in both mammalian and yeast cells, respectively.