Oral glucose effectiveness and metabolic risk in obese children and adolescents.

AIM: To investigate whether GE is affected in children/adolescents with obesity and abnormalities of the metabolic syndrome (MetS). METHODS: Cross-sectional study of oral GE (oGE), insulin sensitivity and secretion (calculated on 5 time-points oral glucose tolerance test) and metabolic abnormalities in 1012 patients with overweight/obesity (aged 6.0-17.9 years old). A MetS risk score was calculated on the basis of distribution of fasting glucose, triglycerides, HDL-cholesterol, total cholesterol, systolic and diastolic blood pressure. Non-alcoholic fatty liver disease (NAFLD) was suspected based on thresholds of alanine aminotransferases. RESULTS: Four-hundred and eighty patients (47.73%) had low-MetS risk score, 488 medium (48.22% with 1-2 risk factors) and 41 (4.05% with ≥ 3 factors) high risk. oGE was significantly lower in subjects with obesity [3.81 (1.46) mg/dl/min- 1] than in those with overweight [4.98 (1.66) mg/dl/min- 1; p value < 0.001]. oGE was negatively correlated with BMI (ρ = - 0.79; p < 0.001) and BMI z score (ρ = - 0.56; p < 0.001) and decreased significantly among MetS risk classes (p = 0.001). The median difference of oGE from low to medium risk was estimated to be as - 4.9%, from medium to high as - 13.38% and from low to high as - 17.62%. oGE was not statistically different between NAFLD+ and NAFLD- cases. CONCLUSIONS: In children and adolescents with obesity oGE decreases. Noteworthy, it decreases as the Met score increases. Therefore, reduced oGE may contribute to the higher risk of these individuals to develop type 2 diabetes.

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.

The rehabilitation of children and adolescents with severe or medically complicated obesity: an ISPED expert opinion document.

Severe/medically complicated obesity in childhood, and particularly in adolescence, is a real disability that requires an intensive and continuous approach which should follow the procedures and schedule of rehabilitation medicine. Given the lack of a specific document focusing on children and adolescents, the Childhood Obesity Study Group set out to explore the available evidence for the treatment of severe or medically complicated obesity and to set standards tailored to the specific context of the Italian Health Service. Through a series of meetings and electronic communications, the writing committee (selected from members of the Study Group) selected the key issues, explored the literature and produced a draft document which was submitted to the other experts until the final synthesis was approved by the group. In brief, the following issues were involved: (1) definition and epidemiology; (2) identification of common goals designed to regain functional competence and limit the progression of metabolic and psychological complications; (3) a multi-professional team approach; (4) the care setting. This paper is an expert opinion document on the rehabilitation of severe and medically complicated obesity in children and adolescents produced by experts belonging to the Childhood Obesity Study Group of the Italian Society for Pediatric Endocrinology and Diabetology (ISPED).

Triglycerides-to-HDL cholesterol ratio as screening tool for impaired glucose tolerance in obese children and adolescents.

AIMS: To identify metabolic phenotypes at increased risk of impaired glucose tolerance (IGT) in Italian overweight/obese children (n = 148, age 5-10 years) and adolescents (n = 531, age 10-17.9 year). METHODS: Phenotypes were defined as follows: obesity by the 95th cut-points of the Center for Disease Control body mass index reference standards, impaired fasting glucose (fasting plasma glucose ≥100 mg/dl), high circulating triglycerides (TG), TG/HDL cholesterol ≥2.2, waist-to-height ratio (WTHR) >0.6, and combination of the latter with high TG or TG/HDL cholesterol ≥2.2. RESULTS: In the 148 obese children, TG/HDL-C ≥ 2.2 (OR 20.19; 95 % CI 2.50-163.28, p = 0.005) and the combination of TG/HDL-C ≥ 2.2 and WTHR > 0.60 (OR 14.97; 95 % CI 2.18-102.76, p = 0.006) were significantly associated with IGT. In the 531 adolescents, TG/HDL-C ≥ 2.2 (OR 1.991; 95 % CI 1.243-3.191, p = 0.004) and the combination with WTHR > 0.60 (OR 2.24; 95 % CI 1.29-3.87, p = 0.004) were associated with significantly increased risk of IGT. In the whole sample, having high TG levels according to the NIH National Heart, Lung and Blood Institute Expert Panel was not associated with an increased risk of presenting IGT. CONCLUSIONS: TG/HDL-C ratio can be useful, particularly in children, to identify obese young patients at risk of IGT. Its accuracy as screening tool in a general population needs to be verified. The combination of TG/HDL-C ratio and WTHR > 0.6 did not improve prediction. Having high TG according to the NIH definition was not associated with increased risk of developing IGT.

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.

Biomarkers of Alzheimer disease, insulin resistance, and obesity in childhood.

OBJECTIVE: To answer the question of whether onset of insulin resistance (IR) early in life enhances the risk of developing dementia and Alzheimer disease (AD), serum levels of 2 molecules that are likely associated with development of AD, the amyloid ß-protein 42 (Aß42) and presenilin 1 (PSEN1), were estimated in 101 preschoolers and 309 adolescents of various BMI. METHODS: Participants (215 boys; 48.8%) were normal weight (n = 176; 40%), overweight (n = 135; 30.7%), and obese (n = 129; 29.3%). The HOmeostasis Model of IR (HOMA-IR), HOMA percent ß-cell function (HOMA-ß) and QUantitative Insulin-sensitivity Check Index (QUICKI) were calculated. RESULTS: Obese adolescents had values of Aß42 higher than overweight and normal-weight peers (190.2 ± 9.16 vs 125.9 ± 7.38 vs 129.5 ± 7.65 pg/mL; P < .0001) as well as higher levels of PSEN1 (2.34 ± 0.20 vs 1.95 ± 0.20 vs 1.65 ± 0.26 ng/mL; P < .0001). Concentrations of Aß42 were significantly correlated with BMI (ρ = 0.262; P < .0001), HOMA-IR (ρ = 0.261; P < .0001) and QUICKI (ρ = -0.220; P < .0001). PSEN1 levels were correlated with BMI (ρ = 0.248; P < .0001), HOMA-IR (ρ = 0.242; P < .0001), and QUICKI (ρ = -0.256; P < .0001). Western blot analysis confirmed that PSEN1 assays measured the full-length protein. CONCLUSION: Obese adolescents with IR present higher levels of circulating molecules that might be associated with increased risk of developing later in elderly cognitive impairment, dementia, and AD.

Insulin sensitivity from preschool to school age in patients with severe obesity.

BACKGROUND: Insulin sensitivity decreases at puberty transition, but little information has been provided on its earlier time-course. Aim of the present study was to describe the time-course of insulin sensitivity in severely obese children at the transition from preschool to school age. RESEARCH DESIGN AND METHODS: Retrospective study of a cohort of 47 severely obese [Body Mass Index (BMI) ≥99° percentile] preschoolers evaluated twice, once between 2 and 6 years of age, and once before age 8. Glucose tolerance, Whole Body Insulin Sensitivity Index (WBISI), Insulinogenic Index (IGI); ß-cell demand index (BCDI) and Insulin Secretion-Sensitivity Index 2 (ISSI-2) were longitudinally estimated during the oral glucose tolerance test. RESULTS: After a median follow-up of 2.23 (1-4.52) y, obese patients showed significant decrease in WBISI (p<0.0001), and increase in fasting (p = 0.005) and 2 h glucose (2HG, p = 0.001). One child in preschool age and 4 school age children presented with 2HG between 7.8-11.1 mmol/l. Best predictors of WBISI, 2HG and BCDI in the school age were changes in BMI z-score (R(2) = 0.309; p = 0.002; ß = -0.556), ISSI-2 (R(2) = 0.465; p<0.0001; ß = -0.682), and BMI z-score (R(2) = 0.246; p = 0.008; 0.496), respectively. CONCLUSIONS: In morbidly obese children, insulin sensitivity seems to decline even before pubertal transition, but changes in total adiposity can only partially explain this variation.