Prevalence of prediabetes in children and adolescents by class of obesity.

BACKGROUND: To evaluate prevalence of prediabetes (impaired fasting glucose, IFG; impaired glucose tolerance, IGT; and high glycated haemoglobin, h-HbA1c) in children and adolescents in relation to class of age and obesity; to appraise association with estimates of insulin metabolism, cardiovascular risk factors and alanine aminotransferase (ALT) levels. METHODS: Study of marginal prevalence (i.e., as function of sex, age and obesity class) of isolated and combined IFG, IGT and h-HbA1c in children (age 4-9.9 years) and adolescents (age 10-17.9 years) and association to blood pressure (BP), total, HDL and non-HDL cholesterol, triglycerides, ALT and insulin sensitivity/secretion indexes. RESULTS: Data of 3110 participants (51% males, 33% children; 33% overweight, 39% obesity class I, 20.5% class II, 7.5% class III) were available. Unadjusted prevalence of prediabetes was 13.9% in children (2.1% IFG, 6.7% IGT, 3.9% h-HbA1c, IFG-IGT 0.06%) and 24.6% in adolescents (3.4% IFG, 9.4% IGT, 5.5% h-HbA1c, IFG-IGT 0.09%). Combined h-HBA1c was found in very few adolescents. Prevalence of prediabetes increased significantly by class of obesity up to 20.5% in children and 31.6% in adolescents. Phenotypes of prediabetes were differently but significantly associated with increased systolic and diastolic BP (by 2-7.3 and ~8 mmHg, respectively), triglycerides (by 23-66 mg/dl), and ALT levels (by 10-22 UI/L) depending on the prediabetes phenotype. CONCLUSION AND RELEVANCE: It is worth screening prediabetes in children aged <10 years old with obesity classes II and III and in adolescents. In those with prediabetes, monitoring of blood pressure, triglycerides and ALT levels must be encouraged.

Childhood Obesity and COVID-19 Lockdown: Remarks on Eating Habits of Patients Enrolled in a Food-Education Program.

Childhood obesity is a worldwide health emergency. In many cases, it is directly linked to inappropriate eating habits and a sedentary lifestyle. During lockdown aimed at containing the coronavirus disease (COVID-19) spread, children have been forced to stay at home. The present study aimed at investigating the lifestyles of outpatients (aged 5-17 years) with complicated obesity enrolled in the day-hospital food education program at the Children's Hospital Bambino Gesù in Rome. A survey was performed based on a structured questionnaire, investigating dietary habits and lifestyles. The questionnaire answers were rated as "yes/no/sometimes" or "often/never/sometimes". Eighty-eight families correctly completed the questionnaire between March and May 2020. The results highlighted that 85.2% (N = 75) of the patients ate breakfast regularly, and 64.3% (N = 72) consumed fruit as an afternoon snack. However, 21.6% (N = 19) did just "often" home workouts, and 50.0% (N = 44) reported an increase of feeling hungry with "sometimes" frequency. There is a significant relationship of feeling hungry with gender (p < 0.0001) and age (p = 0.048) and, also, between gender with having breakfast (p = 0.020) and cooking (p = 0.006). Living a healthy lifestyle during lockdown was difficult for the outpatients, mainly due to the increase in a sedentary lifestyle and the increase in feeling hungry, but some healthy eating habits were maintained, as advised during the food education program provided before lockdown.

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.

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.

Beyond the morphology of the glucose curve following an oral glucose tolerance test in obese youth.

BACKGROUND: To describe the morphology of glucose curve during the oral glucose tolerance test (OGTT) and any association with glucose tolerance, insulin action and secretion in obese youth. STUDY DESIGN: Cross-sectional. METHODS: OGTT data of 553 patients were analysed. Subjects were divided in groups based on the morphology (i.e. monophasic, biphasic, triphasic and upward monotonous) of glucose curve. Insulin action was estimated by the homeostasis model assessment of insulin resistance, the insulin sensitivity, the muscle insulin sensitivity and the hepatic insulin resistance indexes (HIRI), and the oral glucose insulin sensitivity (OGIS). Insulin secretion was estimated by the insulinogenic index (IGI). Disposition index, including the insulin secretion-sensitivity index-2, and areas under glucose (AUC(G)) and insulin (AUC(I)) curves were computed. RESULTS: In patients with normal glucose tolerance (n=522), prevalent morphology of the glucose curve was monophasic (n=285, 54%). Monophasic morphology was associated with the highest concentration of 1 h plasma glucose (P<0.0001) and AUC(G) (P<0.0001); biphasic morphology with better insulin sensitivity as estimated by OGIS (P<0.03) and lower AUC(I) (P<0.0001); triphasic morphology with the highest values of HIRI (P<0.02) and IGI (P<0.007). By combining morphologies of glucose and insulin curves or time of the glucose peak, a deeper characterisation of different phenotypes of glucose metabolism emerged. CONCLUSIONS: Morphologies of the glucose curve seem reflecting different metabolic phenotypes of insulin action and secretion, particularly when combined with morphologies of insulin curve or time of glucose peak. Such findings may deserve validation in cohort study, in which glucose metabolism would be estimated by using gold standard techniques.