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Background: Although an association between insulin resistance (IR) and body adiposity has been reported in obese children, this relationship has not been studied as thoroughly as in adults., Aim: We evaluated the association between oral glucose tolerance testing (OGTT) and percent body fat (PBF) in a sample of 1512 obese children followed at a Pediatric Obesity Clinic., Subjects and Methods: Six hundred and twenty-eight male and 884 female obese children aged 6 to 18 yr were consecutively enrolled into the study. OGTT was performed with administration of 1.75 g of glucose per kg of body weight (up to 75 g). PBF was estimated through bioelectrical impedance analysis (BIA) using a population- specific formula recently published by our group. Multivariable median regression was used to evaluate the association between 4 outcomes [glucose area under the curve (AUC), insulin AUC, insulin sensitivity index (ISI), and insulinogenic index (IGI)] and gender, age or pubertal status and PBF., Results: Median PBF was 52% (range 26 to 70%). After correction for age and gender, a 10% increase of PBF was associated with a decrease of -0.50 [95% confidence interval (CI): -0.65 to -0.35] units of ISI and an increase of 0.15 units of IGI (95%CI 0.07 to 0.24)., Conclusions: In obese children, PBF is inversely associated with IR and directly associated to β-cell response as detected by OGTT.

Physical activity is essential in obesity management because of the impact of exercise-related energy expenditure (EE) and fat oxidation (Fox) rate on a daily balance, but the specific physiological effects of different exercise modalities are scarcely known in obese individuals. The objective of the study was to compare the metabolic responses to treadmill (TM) and cycle ergometer (CE) exercise in obese adolescents. Gas exchange, heart rate (HR), blood lactate (LA) concentration, EE and Fox were determined at different intensity levels (up to about 85% of maximal oxygen uptake) during TM and CE in 14 pubertal (Tanner stage: >3) obese (BMI SDS: 2.15-3.86) male adolescents (age: 13-18 years). At comparable HR, oxygen uptake, EE and Fox were higher, and LA lower, during TM than CE (P<0.05-0.001), suggesting that cycling imposes a metabolic involvement at the level of the single active muscles greater than walking. Therefore, due to different physiological responses to TM and CE, walking was more convenient than cycling in obese adolescents, permitting to attain the same EE at lower HR, with lower blood LA concentration and with greater Fox. These conclusions seem clinically relevant when using exercise as a part of multidisciplinary treatment for juvenile obesity and amelioration of related metabolic disturbances.

We investigated in a young Italian obese population, the relationship between ambulatory BP (ABP) and several pathophysiological factors linking obesity to hypertension. A total of 89 obese children and adolescents underwent a 24-h ambulatory BP monitoring (ABPM) and an oral glucose tolerance test. The circulating levels of insulin, lipids, uric acid, C-reactive protein, interleukin-6, renin and aldosterone and the 24-h urinary levels of epinephrine, norepinephrine and albumin excretion rate were measured. Nine percent of subjects had daytime sustained hypertension (SH), 26% night-time hypertension and 11% a non-dipping pattern. SH subjects compared to those with sustained normotension (SN) were more obese (P<0.05), with a more frequent family history of hypertension (P<0.05), higher urinary catecholamine (P<0.05) and heart rate values (P<0.05) after adjustment for standard deviation score (SDS) of body mass index (BMI) and sex. Subjects with night-time hypertension compared to those with night-time normotension were more obese (P<0.0001), with a higher prevalence of impaired glucose tolerance (P<0.05) and metabolic syndrome (P<0.05) and higher 2-h glucose (P<0.05), uric acid (P<0.05) and triglycerides (P<0.05). In multivariate regression analysis, daytime systolic BP (SBP) remained independently correlated with urinary norepinephrine and SDS-BMI (P<0.05 for both), daytime diastolic BP (DBP) with waist circumference (P<0.05) and night-time SBP and DBP with SDS-BMI (P<0.01 for both). The risk of having systolic and diastolic hypertension increased with the increase in SDS-BMI and waist circumference, respectively. In conclusion, in our cohort of obese children and adolescents, daytime and night-time hypertension were associated with activation of the sympathoadrenal system and worst metabolic conditions, respectively.

Objective: To evaluate predictors of non-alcoholic fatty liver disease (NAFLD) in obese children., Design: Cross-sectional study., Subjects: Two hundred and sixty-eight obese children not consuming alcohol and without hepatitis B or C were consecutively studied at an auxology clinic., Measurements: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl-transferase (GGT), cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, triglycerides, uric acid, glucose, glucose during oral glucose tolerance testing (OGTT), insulin, insulin during OGTT, insulin resistance as estimated by homeostasis model assessment (HOMA), C-reactive protein (CRP), and systolic and diastolic blood pressure were measured. Fatty liver was diagnosed by ultrasonography using standard criteria. Univariable and multivariable logistic regression was used to evaluate predictors of NAFLD. All predictors except gender and pubertal status were modeled as continuous variables., Results: NAFLD was detected in 44% of obese children. At univariable analysis, male gender, Z-score of body mass index (BMI) (Z-BMI), ALT, AST, GGT, triglycerides, uric acid, glucose, glucose during OGTT, insulin, insulin during OGTT, HOMA, CRP and systolic blood pressure were predictors of NAFLD, whereas HDL-cholesterol and late-pubertal status were predictors of the normal liver. At multivariable analysis, however, only Z-BMI, ALT, uric acid, glucose during OGTT and insulin during OGTT were independent predictors of NAFLD., Conclusion: Z-BMI, ALT, uric acid, glucose during OGTT and insulin during OGTT are independent predictors of NAFLD in Italian obese children, with most of the prediction explained by ALT and Z-BMI.

Background and Aim: Several reports have described an increasing prevalence and incidence of type 2 diabetes among children. Limited information is available about the prevalence of impaired glucose tolerance (IGT) and type 2 diabetes in obese children, particularly in Europe. The aim of this study was to examine the prevalence of glucose intolerance and other cardiovascular risk factors in obese children over a 24-year period., Methods and Results: The study population consisted of 1376 consecutive subjects who attended a national centre for the study of obesity between 1979 and 2002. Subjects were divided into three successive 8-year cohorts: cohort 1 (period 1979-1986, n=453, male: 39%), cohort 2 (period 1987-1994, n=409, male: 46%), cohort 3 (period 1995-2002, n=514, male: 48%). All subjects underwent an oral glucose tolerance test. Lipids, blood pressure, uric acid, C-reactive protein (CRP), fasting insulin and birth weight were recorded. Insulin resistance was measured by homeostasis model assessment (HOMA-IR). The degree of obesity was higher in the more recent cohorts (standard deviation score of body mass index: 3.3+/-0.04 vs. 3.7+/-0.04 vs. 3.8+/-0.03, P<0.0001). The proportion of subjects with glucose intolerance was lower in the last two cohorts compared with the first one (11.2% vs. 3.9% vs. 6.0%, P<0.0001). This was predominantly due to changes in the frequency of IGT (9.1% vs. 3.2% vs. 5.4%, P<0.001 in cohorts 1, 2 and 3, respectively) while the prevalence of undiagnosed type 2 diabetes and impaired fasting glucose was similar in the three cohorts (0.9% vs. 0% vs. 0.2% and 1.3% vs. 0.7% vs. 0.4%, respectively). After adjustment for differences in age, sex, pubertal status and birth weight the levels of fasting insulin, HOMA-IR, total cholesterol, triglycerides and blood pressure, were significantly lower in cohorts 2 and 3 than in cohort 1 while CRP and uric acid were higher in the last two cohorts., Conclusion: Over a recent period spanning 24 years, the degree of obesity has risen but the prevalence of glucose intolerance has fallen in obese children admitted to an obesity centre. This was accompanied by an improvement in traditional but a worsening in non-traditional risk factors for cardiovascular disease.

Objective: Studies on the prevalence of metabolic syndrome (MS) in European obese children using child-based criteria are scanty. Moreover, it is unknown if nontraditional cardiovascular disease (CVD) risk factors are associated with the MS at this early age in these subjects., Design and Subjects: We studied the prevalence of the MS in 588 Caucasian obese children and adolescents by devising a World Health Organization derived definition and child-specific criteria, whose deviation from normalcy was based on an age, sex, and ethnically comparable control group of 1363 subjects. In a subgroup of 206 obese children, we investigated the association of the MS with nontraditional CVD risk factors., Measurements: Fasting blood samples for glucose and lipids measurements were taken in both control and obese children. In addition, the obese children underwent an oral glucose tolerance test. In the subgroup of 206 obese children, albumin excretion rate , plasma uric acid, fibrinogen, plasminogen activator inhibitor type 1(PAI-1), C-reactive protein, interleukin 6 and white blood cells were also measured., Results: The prevalence of MS was 23.3%. A similar prevalence of 23% of MS was recorded in the subgroup of 206 obese children in whom measurements of nontraditional CVD risk factors were available. After adjustment for the degree of obesity, subjects with MS had significantly higher uric acid (6.6+/-0.23 vs 6.1+/-0.12 mg/dl, P<0.0001) and PAI-1 plasma concentrations (231.4+/-25.50 vs 214.3+/-12.96 ng/ml, P<0.05) and a higher frequency of microalbuminuria (37 vs 20%, P<0.05) than those without MS. Microalbuminuria, uric acid and PAI-1 explained 10.6% of the variance of MS., Conclusion: Approximately, a quarter of Caucasian obese children have the MS. The association of MS with several nontraditional risk factors for CVD early in life suggests a heightened CVD risk in these individuals.

Several methods have been developed to assess insulin resistance (IR), insulin secretion, and sensitivity: some of them, such as the homeostasis model assessment (HOMA) for IR (HOMA IR) and for insulin secretion (HOMA beta cell) and the quantitative insulin sensitivity check index (QUICKI) are based on fasting levels of glucose (fasting G) and insulin (fasting I); others, such as the pancreatic insulin response to glucose (IRG) and the insulin sensitivity index (ISI) are derived from the glycemic and insulinemic responses to the oral glucose tolerance test (OGTT). The aim of the study was to compare these indexes in a large group of prepubertal and pubertal obese subjects and verify whether the data from fasting samples were enough for evaluating IR and insulin secretion or if OGTT was mandatory. A total of 405 obese subjects (221 boys and 184 girls) was studied. Ninty-three were prepubertal (Tanner stage I), 98 early pubertal (stage II to III) and 214 late pubertal (stage IV to V). In each subject, a 120-minute OGTT was performed, and the glycemic (mean blood glucose [MBG]) and insulinemic (mean serum insulin [MSI]) responses, expressed as AUC/120, as well as IRG and ISI were calculated. The fasting I/fasting G ratio (FIGR), HOMA IR, HOMA beta cell, and QUICKI were then measured. FIGR and HOMA IR increased in both sexes during puberty, but in girls, the increase was already evident from stage I to stage II to III, while in boys, it was evident only from stage II to III to stage IV to V. QUICKI decreased in girls at the onset of puberty and was lower than in boys in stage II to III; on the other hand, HOMA beta cell did not show any variation. IRG increased throughout puberty, although it was higher in boys than in girls in stages II to III and IV to V, while ISI decreased at the onset of puberty in boys; HOMA IR correlated with MSI and IRG, and HOMA beta cell with MSI in pubertal subjects only. In conclusion, the indexes deriving from fasting samples, such as FIGR and HOMA IR, proved to be enough for evaluating IR in prepubertal and pubertal obese subjects, as did QUICKI for insulin sensitivity, However, OGTT is still useful for assessing insulin secretion, because IRG is more sensitive in depicting the pubertal variations of IR than HOMA beta cell., (Copyright 2002, Elsevier Science (USA). All rights reserved.)

Background and Aim: Correlations between serum leptin (LEP) and BMI and the percentage of fat mass (FM), as well as differences between male and female serum levels and their behaviour during weight loss have already been extensively described in adult obesity, whereas few cases have been examined in child and adolescent obesity. There are also few studies of the alterations in NPY in peripheral blood in obese subjects during weight loss., Methods: This study aimed to evaluate the correlations between LEP and BMI, FM% and NPY in 72 obese subjects, with BMI > 35 (29 males and 43 females) aged between 9.6 and 19.8 years old, during weight loss together with any differences between the sexes., Results: LEP was positively correlated in both sexes with BMI and FM%, whereas no correlation emerged with NPY; LEP levels decreased gradually during weight loss, whereas no changes were observed in NPY except during the first phases of weight loss in males when the decrease was significant. LEP concentrations were significantly higher in females, who also showed a higher FM% with equal BMI. No difference was observed between NPY levels in both sexes., Conclusions: The authors conclude that: 1) the behaviour of LEP in child-adolescent obesity is broadly comparable to that described in adult obesity; 2) the highest LEP concentrations with equal BMI in females appear to reflect the different body composition of the two sexes given that females have a higher FM%; 3) the control exerted by LEP on hypothalamic NPY cannot be seen in peripheral blood and no differences emerged between the two sexes.

The well know fact that high blood pressure and impaired glucose tolerance are frequently associated with obesity has suggested that hyperinsulinemia could represent one of the possible pathogenetic connections between obesity and systodiastolic hypertension. With the aim of verifying this hypothesis 67 obese subjects (36 hypertensive and 31 normotensive), males, were admitted to our study. All of the subjects underwent standard OGTT in order to measure their glycemic and insulinemic levels. No differences were found between two groups, as regard age and the degree of obesity; blood pressure values were significantly different (p less than 0.01). No significative differences were detected for glycemic and insulinemic levels between normotensive and hypertensive subjects; basal hyperinsulinemia was detected in a similar percentage (16.6 vs 19.3%) in the two groups. Under these circumstances it is not possible to confirm that hyperinsulinemia is the prominent link between obesity and high blood pressure, as previously observed by others.