Skin dysbiosis and Cutibacterium acnes biofilm in inflammatory acne lesions of adolescents

Acne vulgaris is a common inflammatory disorder affecting more than 80% of young adolescents. Cutibacterium acnes plays a role in the pathogenesis of acne lesions, although the mechanisms are poorly understood. The study aimed to explore the microbiome at different skin sites in adolescent acne and the role of biofilm production in promoting the growth and persistence of C. acnes isolates. Microbiota analysis showed a significantly lower alpha diversity in inflammatory lesions (LA) than in non-inflammatory (NI) lesions of acne patients and healthy subjects (HS). Differences at the species level were driven by the overabundance of C. acnes on LA than NI and HS. The phylotype IA1 was more represented in the skin of acne patients than in HS. Genes involved in lipids transport and metabolism, as well as potential virulence factors associated with host-tissue colonization, were detected in all IA1 strains independently from the site of isolation. Additionally, the IA1 isolates were more efficient in early adhesion and biomass production than other phylotypes showing a significant increase in antibiotic tolerance. Overall, our data indicate that the site-specific dysbiosis in LA and colonization by virulent and highly tolerant C. acnes phylotypes may contribute to acne development in a part of the population, despite the universal carriage of the microorganism. Moreover, new antimicrobial agents, specifically targeting biofilm-forming C. acnes, may represent potential treatments to modulate the skin microbiota in acne

Wrist circumference is associated with systolic blood pressure in a population of overweight/obese children and adolescents.

Wrist circumference is associated with systolic blood pressure in a population of overweight/obese children and adolescents G. Campagna1, S. Zampetti1, F. Lucantoni1, M. Capizzi1, L. Marandola1, C. Chiesa2, L. Pacifico3, A. Vania4, R. Buzzetti1; 1Experimental Medicine, Sapienza, University of Rome, 2National Research Counci, Institute of Translational Pharmacology, 3Policlinico Umberto I Hospital, Sapienza, University of Rome, 4Pediatric, Sapienza, University of Rome, Rome, Italy. Background and aims: Insulin resistance, according to many pathophysiological models is one of the most important cardiovascular (CV) risk factors. In a previous study, we demonstrated that the wrist circumference is a clinical marker for insulin-resistance in overweight/obese children and adolescents. Hypertension is another relevant cardiovascular risk factor and obesity is one of its major determinants in children. Various indexes of obesity, such as body mass index (BMI), waist circumference (WC), waist-to-hip ratio and neck circumference, are associated with a high risk of hypertension. The aim of the present study was to investigate a possible association between the wrist circumference and systolic (S) and diastolic (D) blood pressure (BP) in a population of overweight/obese children and adolescents. Materials and methods: N=1133 overweight/obese children and adolescents (580 boys and 553 girls) were consecutively enrolled. In all children and adolescents, body weight, height, SBP, DBP,wrist circumference, SDS-BMI, fasting glucose, fasting insulin levels, and lipid profiles were evaluated at entry. Insulin resistance was estimated according to the homeostasis model assessment of insulin resistance (HOMA-IR). Subjects were evaluated by a doctor for the pubertal stages. Shapiro-Wilk test was used to verify the normality of distribution of continuous variables. The dependent variables for this study were SBP and diastolic DBP; independent variables were SDS-BMI and wrist circumference adjusted for Tanner stage. Multivariate linear regression analyses were used to investigate the influence of independent variables on the variance of blood pressure. All analyses were performed using Statistical Analysis Software (SAS v.9.3). Results: The frequency of hypertension was 22.6% in males and 28.2% in females (p=0.048). Results of the multivariate regression analysis performed in the 1133 children and adolescents stratified according to gender, using wrist circumference and SDS-BMI as independent variable and blood pressure as the dependent variables showed that SBP was significantly associated with wrist circumference and SDS-BMI both in males and females (p≤0.04 for both comparison). We found no association between DBP and wrist circumference in both gender. Wrist circumference and SDS-BMI together explained 21% of the variance of SBP in males and 18% in females. To evaluate the contribution of wrist circumference and SDS-BMI, respectively, to explained variance (R2) of SBP index, we used the backward method. The total variance of SBP was explained by wrist circumference for 17% and by SDS-BMI for 2.7% in males; and by wrist circumference for 14% and SDS-BMI 1% in females. Conclusion: The wrist circumference in overweight/obese children and adolescents is correlated with SBP, confirming that this bone anthropometric marker could be useful for the prediction of cardiovascular risk being correlated with insulin resistance and its deleterious effects. Disclosure: G. Campagna: None

Gender-dependent association of type 2 diabetes with the vasoactive intestinal peptide receptor 1

Type 2 diabetes is characterized by an inadequate pancreatic beta-cell response to the progressive insulin resistance. Its pathogenesis is complex and has been connected with a state of preclinical chronic inflammation. Vasoactive intestinal peptide (VIP) and its receptors play a relevant role in the homeostasis of insulin secretion as well as in the control of inflammation. In particular, VIP receptor 1 (VPAC1) has been found to be down-modulated during inflammation, and to be associated with several diseases. The objective of this study was to compare the distribution of SNPs mapping in the VIP receptor 1 gene in cases with type 2 diabetes and matched controls. Seven hundred cases with type 2 diabetes (423 males and 277 females) and 830 random controls (419 males and 411 females) were analyzed for the distribution of three common SNPs mapping in the VPAC1 gene. The results show a significantly different genotype distribution of the SNP rs9677 in the 3'-UTR of VPAC1 in female cases with type 2 diabetes compared to gender-matched controls (ptrend = 6 x 10(-4)). The rs9677 CC genotype confers the highest risk (OR: 2.1) and correlates with worse clinical parameters such as higher level of total cholesterol, higher LDL/HDL ratio and a higher HbA1c concentration. The genetic association reported here indicates that VIP/VPAC1 signaling can be a relevant pathway in the pathogenesis of type 2 diabetes in females suggesting that at least some aspects of the genetic predisposition to this disease can be gender-specific. (C) 2011 Elsevier B.V. All rights reserved

GAD and IA-2 autoantibody detection in type 1 diabetic patient saliva

Abstract Some attempts have been made in assaying glutamic-acid decarboxylase autoantibodies (GADA) in type 1 diabetic patient (T1DM) saliva. However, these salivary assays did not show sufficient sensitivity and specificity in comparison to serum assays. In this study we evaluated the ability of a fluid-phase 35S-radioimmunoassay to detect GADA and tyrosine phosphatase 2 autoantibodies (IA-2A) in 70 T1DM, 24 T1DM first degree relatives (FDR) and 76 healthy subject saliva. Paired saliva and serum samples were collected from each subject and analyzed. GADA were detected in 45/70 (64.3%) sera and 43/70 (61.4%) T1DM saliva, respectively. IA-2A were detected in 33/70 (47.1%) sera and 30/70 (42.9%) T1DM saliva, respectively. All FDR serum/saliva samples were autoantibody negative. In conclusion, we here report that GADA and IA-2A are detectable with high sensitivity and specificity in human saliva, a specimen which can be easily collected by non-invasive procedures and may represent a reliable tool for the study of T1DM autoimmunit

IgA Anti-transglutaminase Autoantibodies at Type 1 Diabetes Onset Are Less Frequent in Adult Patients and Are Associated With a General Celiac-Specific Lower Immune Response in Comparison With Nondiabetic Celiac Patients at Diagnosis

OBJECTIVE-To evaluate the celiac-associated humoral autoimmunity in child, adolescent, and adult patients at type 1 diabetes (DM1) onset and to determine whether DM1 celiac-specific humoral immunoreactivity occurs similarly to that in nondiabetic patients at celiac disease (CD) diagnosis. RESEARCH DESIGN AND METHODS-IgA anti-transglutaminase autoantibody (IgA-tTGAb) was detected in 654 new-onset DM1 sera. IgA-tTGAb DM1 sera were subsequently analyzed for IgG-tTG, deamidated gliadin (DGP), and actin antibodies, and results were compared with those found in 83 screen-detected nondiabetic patients at CD diagnosis. RESULTS-A total of 12.8% DM1 sera were IgA-TGAb(+), with a lower autoantibody frequency in adult patients aged >18 years (6.8 vs. 15.1%, aged <= 18 years; P = 0.005). IgA-tTGAb titers, IgG-tTGAb, and DGPAb frequency/titers and mean number of celiac-autoantibody positivities per patient were significantly lower in IgA-tTGAb(+) DM1 compared with nondiabetic CD patients. CONCLUSIONS-Age of diabetes onset is negatively associated with risk of CD. The celiac-specific humoral immunoreactivity at DM1 onset is significantly lower compared with that found in nondiabetic patients at CD diagnosis. Diabetes Care 35:2083-2085, 201

Relation Between Wrist Circumference and Left Ventricular Structure in Overweight Children

The aim of this study was to assess the relation of wrist circumference with changes in left ventricular (LV) structure in a population of overweight/obese children and adolescents. One hundred and six children and adolescents were consecutively enrolled. In all subjects body weight, height, wrist circumference, waist circumference, body mass index–standard deviation score, fasting glucose, insulin, lipid profile, and blood pressure were evaluated. All subjects underwent echocardiographic assessment, and the following parameters were evaluated: LV dimension at end diastole and LV dimension at end systole, LV posterior wall thickness at end diastole and LV posterior wall thickness at end systole, interventricular septal thickness at end diastole and interventricular septal thickness at end systole, LV mass, and epicardial adipose tissue (EAT). LV hypertrophy was defined as LVM Index ≥95th percentile. Wrist circumference correlated with all parameters of LV dimensions and LV mass (p <0.0001) and EAT (p = 0.04). The strongest correlations were reported between wrist circumference with LV dimension at end diastole and LV dimension at end systole (r = 0.73 and r = 0.68 respectively, p <0.0001, for both). Results of the multivariate regression analysis showed that wrist circumference was significantly associated with all parameters of LV dimensions, LV mass, and EAT (p ≤0.002). The logistic regression showed that wrist circumference was significantly associated with LV hypertrophy (odds ratio 1.39, p = 0.046). In conclusion, wrist circumference could be a useful measure of cardiovascular risk in obese children and adolescents, opening new perspectives in the prediction of cardiovascular diseases