Fecal microbiota signatures of insulin resistance, inflammation, and metabolic syndrome in youth with obesity: a pilot study.

AIMS: To identify fecal microbiota profiles associated with metabolic abnormalities belonging to the metabolic syndrome (MS), high count of white blood cells (WBCs) and insulin resistance (IR). METHODS: Sixty-eight young patients with obesity were stratified for percentile distribution of MS abnormalities. A MS risk score was defined as low, medium, and high MS risk. High WBCs were defined as a count ≥ 7.0 103/µL; severe obesity as body mass index Z-score ≥ 2 standard deviations; IR as homeostatic assessment model algorithm of IR (HOMA) ≥ 3.7. Stool samples were analyzed by 16S rRNA-based metagenomics. RESULTS: We found reduced bacterial richness of fecal microbiota in patients with IR and high diastolic blood pressure (BP). Distinct microbial markers were associated to high BP (Clostridium and Clostridiaceae), low high-density lipoprotein cholesterol (Lachnospiraceae, Gemellaceae, Turicibacter), and high MS risk (Coriobacteriaceae), WBCs (Bacteroides caccae, Gemellaceae), severe obesity (Lachnospiraceae), and impaired glucose tolerance (Bacteroides ovatus and Enterobacteriaceae). Conversely, taxa such as Faecalibacterium prausnitzii, Parabacterodes, Bacteroides caccae, Oscillospira, Parabacterodes distasonis, Coprococcus, and Haemophilus parainfluenzae were associated to low MS risk score, triglycerides, fasting glucose and HOMA-IR, respectively. Supervised multilevel analysis grouped clearly "variable" patients based on the MS risk. CONCLUSIONS: This was a proof-of-concept study opening the way at the identification of fecal microbiota signatures, precisely associated with cardiometabolic risk factors in young patients with obesity. These evidences led us to infer, while some gut bacteria have a detrimental role in exacerbating metabolic risk factors some others are beneficial ameliorating cardiovascular host health.

Percentiles of serum uric acid and cardiometabolic abnormalities in obese Italian children and adolescents.

BACKGROUND: To investigate the association of serum uric acid (SUA) with cardiometabolic abnormalities in Caucasian overweight/obese children (<10 years of age) versus adolescents (≥10 years of age) by drawing age and gender specific percentiles of uric acid. METHODS: Cross-sectional evaluation of 1364 Caucasian overweight/obese patients (age 4.1-17.9 years; 726 males, 53%; 560 children, 41%). RESULTS: SUA levels were significantly lower in children than in adolescents (4.74 ± 1.05 vs. 5.52 ± 1.49 mg/dl, p < 0.001) and peaked in 12-14 years-old boys and 10-12 years-old girls. In children with levels of SUA in the highest quartile (N = 75, 13%), OR for high triglycerides was 4.145, 95% CI 1.506-11.407 (p = 0.009). In adolescents with SUA in the highest quartile (N = 274, 34%), ORs for insulin resistance was 2.399 (95%CI 1.4-4.113; p < 0.001); for impaired fasting glucose 2.184 (95% CI 0.877-5.441; p = 0.07); for impaired glucose tolerance 2.390 (95% CI 1.405-4.063; p = 0.001); and for high triglycerides 1.8, (95%CI 0.950-3.420; p = 0.05). Multivariable random-effect linear regression models demonstrated that waist circumference and age (p < 0.0001 for both) are the variables most significantly predicting SUA levels, followed by triglycerides (p = 0.005) and 2 h glucose (p = 0.03) while HOMA-IR and BMI z-score did not predict SUA. CONCLUSIONS: High uric acid is associated with metabolic abnormalities and particularly with waist circumference very early in childhood.

Energy Balance-Related Behaviors, Perinatal, Sociodemographic, and Parental Risk Factors Associated with Obesity in Italian Preschoolers.

OBJECTIVE: The obesity epidemic stems from the complex interplay between genetics and environmental factors. Identifying age-specific risk factors in preschoolers may allow implementing more effective intervention strategies. The aim of the present investigation was to examine the association of overweight/obesity with several perinatal, parental, socioeconomic status (SES), and lifestyle-related risk factors in a large sample of Italian preschoolers. METHODS: One thousand eleven children (age 2.0 to 5.7 years) were included in the study. Family pediatricians measured weight and height and collected information on obesity risk factors by means of questionnaires. Perinatal risk factors were recalled from electronic medical records. Weight status was defined according to cutoffs of the International Obesity Task Force (IOTF). RESULTS: Seven hundred sixty-four children (75.6%) were normal weight, and 247 (24.4%) were overweight/obese. Multivariate analysis showed that skipping breakfast (odds ratio [OR] = 3.7; 95% confidence interval [CI], 1.32-10.51), daily drinking of sugar-sweetened beverages (OR = 2.0; 95% CI, 1.02-4.03), meat consumption <5 times/week (OR = 2.2; 95% CI, 1.11-4.57), and formula feeding (OR = 2.1; 95% CI, 0.8-4.5) were significantly (p < 0.05) associated with increased risk of obesity. CONCLUSIONS: Though exclusive formula or mixed feeding represents an age-specific risk factor for overweight/obesity, lifestyle factors associated with increased risk in Italian preschoolers include habits that are common to school-age children, such as skipping breakfast and consumption of sugar-sweetened beverages. The reduced consumption of meat emerged as a risk factor for overweight/obesity, but future research is required to better understand this relationship. Our data suggest, on the whole, that prevention of such unhealthy behaviors must be pursued in preschoolers by means of age-specific interventions.

Reference ranges of HOMA-IR in normal-weight and obese young Caucasians.

AIMS: Insulin resistance (IR) may develop very early in life being associated with occurrence of cardiometabolic risk factors (CMRFs). Aim of the present study was to identify in young Caucasians normative values of IR as estimated by the homeostasis model assessment (HOMA-IR) and cutoffs diagnostic of CMRFs. METHODS: Anthropometrics and biochemical parameters were assessed in 2753 Caucasians (age 2-17.8 years; 1204 F). Reference ranges of HOMA-IR were defined for the whole population and for samples of normal-weight and overweight/obese individuals. The receiver operator characteristic analysis was used to find cutoffs of HOMA-IR accurately identifying individuals with any CMRF among total cholesterol and/or triglycerides higher than the 95th percentile and/or HDL cholesterol lower than the 5th for age and sex, impaired glucose tolerance, and alanine aminotransferase levels ≥40 U/l. RESULTS: Overweight/obese individuals had higher HOMA-IR levels compared with normal-weight peers (p < 0.0001) at any age. HOMA-IR index rose progressively with age, plateaued between age 13 and 15 years and started decreasing afterward. HOMA-IR peaked at age 13 years in girls and at 15 years in boys. The 75th percentile of HOMA-IR in the whole population (3.02; AUROC = 0.73, 95 % CI = 0.70-0.75), in normal-weight (1.68; AUROC = 0.76, 95 % CI = 0.74-0.79), and obese (3.42; AUROC = 0.71, 95 % CI = 0.69-0.72) individuals identified the cutoffs best classifying individuals with any CMRF. CONCLUSIONS: Percentiles of HOMA-IR varied significantly in young Caucasians depending on sex, age, and BMI category. The 75th percentile may represent an accurate cutoff point to suspect the occurrence of one or more CMRFs among high total cholesterol and triglycerides, low HDL cholesterol, and ALT ≥ 40 UI/l.

[Obesity and cardiovascular risk in children]. / Obesità e rischio cardiovascolare in età pediatrica.

Prevalence of overweight and obesity in childhood has substantially increased worldwide in recent decades with children becoming obese at progressively younger ages. Obesity in children carries a wide range of serious complications, and contributes to an increased prevalence of cardiovascular risk factors such as hypertension, hypertrygliceridema, low high-density lipoprotein cholesterol (HDL), impaired glucose metabolism and early atherosclerotic changes not only in adulthood but since in very early pediatric age. In the ORIGIN study (Outcome Reduction with an Initial Glargine Intervention), cardiometabolic risk factors including fatty liver were already detectable in preschoolers at the onset of overweight/obesity despite short-term exposure to excess weight and fairly reduced insulin sensitivity. These facts together with the evidence that early cardiometabolic impairment reverts with lifestyle intervention in pediatric age, emphasize the need to start prevention of childhood obesity and screening of cardiometabolic co-morbities at the earliest stage with multidisciplinary strategies.

Origin of cardiovascular risk in overweight preschool children: a cohort study of cardiometabolic risk factors at the onset of obesity.

IMPORTANCE: To date, the relationship among adiposity, insulin resistance, and cardiovascular risk factors at the onset of overweight or obesity has been unexplored. OBJECTIVES: To assess whether insulin resistance and metabolic abnormalities are detectable at the onset of obesity and to unravel the interplay among adiposity, insulin resistance, and other such abnormalities. DESIGN, SETTING, AND PARTICIPANTS: The Origin of Cardiovascular Risk in Overweight Preschool Children cohort study aimed to evaluate at the onset of obesity in preschool children the prevalence of metabolic abnormalities, including hypertension, dyslipidemia, impaired carbohydrate metabolism, and nonalcoholic fatty liver disease. Between July 1, 2011, and July 30, 2012, in the Rome municipality, 13 family pediatricians enrolled healthy children (age range, 2.0-5.8 years) in the study during their routine practice of growth monitoring. Clinical medical records of 5729 children were reviewed; 597 children manifested new-onset overweight or obesity as their body mass index changed from normal weight to overweight or obesity in the previous 12 months according to the International Obesity Task Force classification. Of them, 219 were studied. MAIN OUTCOMES AND MEASURES: Patients with new-onset overweight or obesity underwent clinical laboratory testing, including oral glucose tolerance test, and ultrasonographic investigations of fatty liver and intimal medial thickness of the common carotid arteries, subcutaneous adipose tissue, and visceral adipose tissue. The homeostatic assessment model algorithm-insulin resistance was calculated. RESULTS: Among the entire population (n = 5729), overweight increased from 7.0% at 2.0 years to 16.9% at 5.8 years, with corresponding figures of 1.1% to 2.9% for obesity. In total, 597 overweight or obese children (10.4%) were identified, and 219 of them (36.7%) were studied. Among the latter, 86 patients (39.3%) had at least 1 metabolic abnormality. Hypertension was diagnosed in 29 patients (13.2%), dyslipidemia in 55 patients (25.1%), impaired fasting glucose level in 7 patients (3.2%), and glucose intolerance in 6 patients (2.7%). Nonalcoholic fatty liver disease was diagnosed in 68 patients (31.1%). CONCLUSIONS AND RELEVANCE: Cardiometabolic risk factors, including fatty liver, are detectable in preschoolers at the onset of overweight or obesity, despite short-term exposure to excess weight and reduced insulin sensitivity. Our findings suggest the need to screen for cardiometabolic abnormalities at an earlier age than is now recommended.

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-tTGAb(+), 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.

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

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 (35)S-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 autoimmunity.

Use of continuous subcutaneous insulin infusion in patients with cystic fibrosis related diabetes: three case reports.

UNLABELLED: We used insulin pump therapy in three patients (two males and one female; age 5.5, 21 and 28.2 years, respectively) with CFRD and we reported the experience of 2 years of follow-up. In all the patients during the CSII treatment, the annual mean level of HbA1c reduced and the annual mean level of BMI increased, respected, the year before starting the CSII (in MDI treatment with 4 injections/day). The insulin requirements decreased during the CSII treatment and respected MDI treatment. During the CSII treatment, none of the patients exhibited episodes of DKA or severe hypoglycaemia. Only two episodes of lipohypertrophy and a slight local cutaneous inflammation were reported. CONCLUSIONS: The use of CSII in our patients with CFRD improves the metabolic control of diabetes and the nutritional status with no concomitant problems related to this treatment.