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.

Inside out the Ragbag of Glucose Intolerance in Obese Adolescents.

BACKGROUND/AIMS: The prevalence of impaired glucose tolerance (IGT) is rising among obese adolescents in parallel with epidemic obesity. In some cases, IGT reverts to normal glucose tolerance (NGT) by the end of puberty. The aims of the present study were to investigate metabolic factors determining changes over time of glucose at 120 min (Glu120) following an oral glucose tolerance test (OGTT), and to verify whether preserved ß-cell glucose sensitivity (ßCGS) protects against persistent IGT. METHODS: We performed a cohort study of 153 severely obese children and adolescents evaluated with a 5-point OGTT at baseline and at follow-up with measurements of glucose, insulin, and C-peptide to estimate several empirical parameters of insulin sensitivity (includ ing oral glucose insulin sensitivity [OGIS] and OGTT-derived glucose effectiveness) and secretion. RESULTS: At follow-up (range 0.9-4.8 year), 113 (73.9%) patients remained with NGT, 9 (5.9%) had IGT, and 28 (18.3%) had reverted to NGT; 3 NGT patients had developed IGT. In multivariable models, change in loge(ßCGS) was inversely associated with time-related change in loge(Glu120), with (model 2) and without (model 1) correction for the change in loge(OGIS). Model 2 was more strongly associated with change in loge(Glu120). CONCLUSIONS: Changes in ßCGS and insulin sensitivity were inversely associated with changes in Glu120 at follow-up, contributing a likely explanation for the reversal of IGT to NGT.

Childhood obesity classification systems and cardiometabolic risk factors: a comparison of the Italian, World Health Organization and International Obesity Task Force references.

BACKGROUND: Body Mass Index Italian reference data are available for clinical and/or epidemiological use, but no study compared the ability of this system to classify overweight and obesity and detect subjects with clustered cardiometabolic risk factors with international standards. Therefore our aim was to assess 1) the agreement among the Italian Society for Pediatric Endocrinology and Diabetology (ISPED), the World Health Organisation (WHO) and the International Obesity Task Force (IOTF) Body Mass Index cut-offs in estimating overweight or obesity in children and adolescents; 2) the ability of each above-mentioned set of cut-points to detect subjects with cardiometabolic risk factors. METHODS: Data of 6070 Italian subjects aged 5-17 years were collected. Prevalence of normal-weight, overweight and obesity was determined using three classification systems: ISPED, WHO and IOTF. High blood pressure, hypertriglyceridemia, low high density lipoprotein-cholesterol and impaired fasting glucose were considered as cardiometabolic risk factors. RESULTS: ISPED and IOTF classified more subjects as normal-weight or overweight and less subjects as obese as compared to WHO (p <0.0001) in the whole sample and in groups divided by gender and age. The strength of agreement between the three methods compared to each other was excellent for overweight (including obesity) definition (k > 0.900), while it differed for obesity definition, ranging from the highest agreement between ISPED and IOTF (k 0.875) to the lowest between ISPED and WHO (k 0.664). WHO had the highest sensitivity, while ISPED and IOTF systems had the highest specificity, in identifying obese subjects with clustered cardiometabolic risk factors. Analogous results were found in subjects stratified by gender or age. CONCLUSIONS: ISPED and IOTF systems performed similarly in assessing overweight and obesity, and were more specific in identifying obese children/adolescents with clustered cardiometabolic risk factors; on the contrary, the WHO system was more sensitive. Given the seriousness of the obesity epidemic, we wonder whether the WHO system should be preferable to the national standards for clinical practice and/or obesity screening.

Insulin dynamics in young women with polycystic ovary syndrome and normal glucose tolerance across categories of body mass index.

BACKGROUND: Evidence favours insulin resistance and compensatory hyperinsulinemia as the predominant, perhaps primary, defects in polycystic ovary syndrome (PCOS). The aim of the present study was to evaluate insulin metabolism in young women with PCOS but normal glucose tolerance as compared with age, body mass index and insulin resistance-matched controls to answer the question whether women with PCOS hypersecrete insulin in comparison to appropriately insulin resistance-matched controls. RESEARCH DESIGN AND METHODS: Sixty-nine cases were divided according to their body mass index (BMI) in normal-weight (N = 29), overweight (N = 24) and obese patients (N = 16). Controls were 479 healthy women (age 16-49 y). Whole body Insulin Sensitivity (WBISI), fasting, and total insulin secretion were estimated following an oral glucose tolerance test (C-peptide deconvolution method). RESULTS: Across classes of BMI, PCOS patients had greater insulin resistance than matched controls (p<0.0001 for all the comparisons), but they showed higher fasting and total insulin secretion than their age, BMI and insulin resistance-matched peers (p<0.0001 for all the comparisons). CONCLUSION: Women with PCOS show higher insulin resistance but also larger insulin secretion to maintain normal glucose homeostasis than age-, BMI- and insulin resistance-matched controls.

Systematic review of metformin use in obese nondiabetic children and adolescents.

OBJECTIVE: Childhood obesity has become epidemic and has been accompanied by an increase in prevalence of type 2 diabetes (T2DM) in youth. Addressing obesity and insulin resistance by drug treatment represents a rational strategy for the prevention of T2DM. A systematic review was performed to evaluate the effectiveness of metformin in reducing weight and ameliorating insulin resistance in obese nondiabetic children. METHODS: A PubMed database search was conducted, using 'metformin', 'obesity', 'insulin resistance', 'children', 'adolescents' as search terms. RESULTS: Eleven trials were included in the present review. Metformin was administered for 6-12 months at a dosage of 1,000-2,000 mg/daily, decreasing BMI by 1.1-2.7 compared with placebo or lifestyle intervention alone. Concomitantly, fasting insulin resistance improved after metformin therapy. Posttreatment follow-up was performed in one study, showing that after 1 year of discontinuation of therapy the decrease in BMI disappears. CONCLUSIONS: Short-term metformin treatment appears to moderately affect weight reduction in severely obese children and adolescents, with a concomitant improvement in fasting insulin sensitivity. Further studies with longer treatment period are needed to establish how much metformin can reduce weight and its real utility in preventing T2DM development in pediatric patients.

IGF2 methylation is associated with lipid profile in obese children.

AIM: Our aim was to investigate the relationships between the degree of IGF2 methylation and the metabolic status in obese children and adolescents. SUBJECTS AND METHODS: Eighty-five obese subjects aged 11.6 ± 2.1 years were studied. Anthropometry, metabolic parameters, blood pressure and body composition were assessed. DNA methylation analysis was performed by restriction enzyme digestion assay. The study population was subdivided into two groups according to the percentage of IGF2 cytidine-guanosine (CpG) island methylation. RESULTS: Twenty-two subjects showed intermediate methylation (a percentage of CpG site methylation comprised between 10 and 60%), 56 were hypomethylated (percentage of methylation lower than 10%), and only 1 showed a high rate of hypermethylation (percentage of methylation above 60%). Children with intermediate methylation showed significantly higher levels of triglycerides (107.6 ± 41.99 vs. 76.6 ± 30.18 mg/dl, p < 0.005) and a higher triglyceride/high-density lipoprotein-cholesterol ratio (2.23 ± 0.98 vs. 1.79 ± 0.98, p < 0.02) compared with hypomethylated children. CONCLUSIONS: These preliminary findings show for the first time a relationship between IGF2 methylation pattern and lipid profile in obese children. Although the correlation does not imply causation, if our findings are confirmed in further studies, IGF2 methylation might represent an epigenetic marker of metabolic risk.

Fatty liver and insulin resistance in children with hypobetalipoproteinemia: the importance of aetiology.

OBJECTIVE: Hepatic steatosis is strongly associated with insulin resistance, but causative mechanisms that link these conditions are still largely unknown. Nowadays, it is difficult to establish whether fatty liver is the cause of insulin resistance or instead the complex metabolic derangements of insulin resistance determine hepatic steatosis and its progression to fibrosis. In patients with familial hypobetalipoproteinemia (FHBL), hepatic steatosis is because of the genetically determined defective form of apolipoprotein B, independently of metabolic derangements. Therefore patients with FHBL represent a good in vivo model to evaluate the relationships between fatty liver and insulin sensitivity. METHODS: We evaluated insulin resistance through HOMA-IR in 60 children with echografic and histological features of steatosis; 30 of whom had nonalcoholic fatty liver disease (NAFLD) and 30 had FHBL. RESULTS: All patients had histological features of hepatic steatosis. Patients with FHBL were hypolipidemic, as expected. No significant differences between two groups were observed in liver function tests. IRI and HOMA-IR were statistically higher in NAFLD subjects compared to the FHBL group. CONCLUSION: In our study, we demonstrated that in children with FHBL, hepatic steatosis is dissociated from insulin resistance. This finding suggests that fat accumulation per se may be not a sufficient causal factor leading to insulin resistance, and that other mediators may be involved in the development of alteration in glucose metabolism and metabolic syndrome in patients with NAFLD.

Severe obesity and cardiometabolic risk in children: comparison from two international classification systems.

OBJECTIVES: There is no agreed-upon definition for severe obesity (Sev-OB) in children. We compared estimates of Sev-OB as defined by different cut-points of body mass index (BMI) from the Centers for Disease Control and Prevention (CDC) or the World Health Organization (WHO) curves and the ability of each set of cut-points to screen for the presence of cardiometabolic risk factors. RESEARCH DESIGN AND METHODS: Cross-sectional, multicenter study involving 3,340 overweight/obese young subjects. Sev-OB was defined as BMI ≥ 99(th) percentile or ≥ 1.2 times the 95(th) percentile of the CDC or the WHO curves. High blood pressure, hypertriglyceridemia, low High Density Lipoprotein -cholesterol and impaired fasting glucose were considered as cardiometabolic risk factors. RESULTS: The estimated prevalence of Sev-OB varied widely between the two reference systems. Either using the cut-point ≥ 99(th) percentile or ≥ 1.2 times the 95(th) percentile, less children were defined as Sev-OB by CDC than WHO (46.8 vs. 89.5%, and 63.3 vs. 80.4%, respectively p<0.001). The CDC 99(th) percentile had lower sensitivity (58.5 vs 94.2), higher specificity (57.6 vs 12.3) and higher positive predictive value (34.4 vs 28.9) than WHO in identifying obese children with ≥ 2 cardiometabolic risk factors. These differences were mitigated using the 1.2 times the 95(th) percentile (sensitivity 73.9 vs. 88.1; specificity 40.7 vs. 22.5; positive predictive value 32.1 vs. 30.1). Substantial agreement between growth curves was found using the 1.2 times the 95(th) percentile, in particular in children ≤ 10 years. CONCLUSIONS: Estimates of Sev-OB and cardiometabolic risk as defined by different cut-points of BMI are influenced from the reference systems used. The 1.2 times the 95(th) percentile of BMI of either CDC or WHO standard has a discriminatory advantage over the 99(th) percentile for identifying severely obese children at increased cardiometabolic risk, particularly under 10 years of age.

Thyroid function tests in obese prepubertal children: correlations with insulin sensitivity and body fat distribution.

BACKGROUND/AIMS: Elevated thyroid-stimulating hormone (TSH) concentrations in association with normal/slightly elevated free triiodothyronine (fT(3)) and/or free thyroxine (fT(4)) have been consistently found in obese children. To examine relationships between adiposity, insulin sensitivity, and TSH, fT(3) and fT(4). METHODS: 240 overweight/obese prepubertal children were studied. Fasting TSH, fT(3), fT(4), glucose, insulin, C-peptide, lipids, leptin and adiponectin were evaluated. Insulin sensitivity and resistance were estimated [quantitative insulin check index (QUICKI), insulin sensitivity index (ISI), and hepatic insulin resistance index]. Body fat was measured by dual-energy X-ray absorptiometry. The central obesity index was calculated as the ratio of fat tissue in the trunk region to fat tissue in the leg region. RESULTS: The multiple regression analysis with age, gender and measures of fatness as covariates showed that QUICKI was the only significant negative predictor of TSH and central obesity index the strongest positive predictor of fT(3), in association with either age or hepatic insulin resistance index, and that the only positive determinant of fT(4) was hepatic insulin resistance index. CONCLUSIONS: Reduced insulin sensitivity is associated with augmented TSH and fT(4), while progressive central fat accumulation is strictly related to a parallel increase in fT(3) levels, independently from total body fat. Further studies are needed to understand mechanisms linking thyroid function to insulin sensitivity and body composition in obese children.

Metabolic syndrome in italian obese children and adolescents: stronger association with central fat depot than with insulin sensitivity and birth weight.

Aim. To evaluate whether body fat distribution, birth weight, and family history for diabetes (FHD) were associated with metabolic syndrome (MetS) in children and adolescents. Methods. A total of 439 Italian obese children and adolescents (5-18 years) were enrolled. Subjects were divided into 2 groups: prepubertal and pubertal. MetS was diagnosed according to the adapted National Cholesterol Education Program criteria. Birth weight percentile, central obesity index (measured by dual-energy X-ray absorptiometry), insulin sensitivity (ISI), and disposition index were evaluated. Multivariate logistic regression models were used to determine variables associated with MetS. Results. The prevalence of MetS was 17%, with higher percentage in adolescents than in children (21 versus 12%). In the overall population, central obesity index was a stronger predictor of MetS than insulin sensitivity and low birth weight. When the two groups were considered, central fat depot remained the strongest predictor of MetS, with ISI similarly influencing the probability of MetS in the two groups and birth weight being negatively associated to MetS only in pubertal individuals. Neither FHD nor degree of fatness was a significant predictor of MetS. Conclusion. Simple clinical parameters like increased abdominal adiposity and low birth weight could be useful tools to identify European obese adolescents at risk for metabolic complications.

Usefulness of ambulatory blood pressure monitoring and head-up tilt test in the evaluation of paediatric syncope.

OBJECTIVES: The aim of this study was to investigate the usefulness of ambulatory blood pressure monitoring versus head-up tilt test in the evaluation of children with a history of syncope. STUDY DESIGN: We considered 146 consecutive children with more than one episode of syncope. All patients had a normal electrocardiogram at rest and were otherwise considered to be healthy. Forty-six patients,19 male, with a mean age of 13.6 plus or minus 5.6 years, were studied with a head-up tilt test and 100 patients, 41 male with a mean age of 9.4 plus or minus 5.6 years, were studied with ambulatory blood pressure monitoring. Twelve patients underwent both procedures. Hypotension during ambulatory blood pressure monitoring was defined when mean blood pressure values were lower than the 50th centile and the head-up tilt test was positive when syncope occurred. All patients were followed for 10 plus or minus 2 months. RESULTS: Ambulatory blood pressure monitoring showed postural hypotension in 91% children, while head-up tilt test was positive for 54%. In the group of children having both tests, two of them were negative for both, 10 of 12 children had a positive ambulatory blood pressure monitoring while only five of 10 children had a positive response to head-up tilt test. CONCLUSIONS: When a child with a normal resting electrocardiogram is referred with a typical history of syncope, the use of ambulatory blood pressure monitoring as a non-invasive first step for diagnosis of postural hypotension may be more sensitive than the head-up tilt test. Behavioural adjustments resolved the continued syncope in most cases. If episodes persist then the head-up tilt test is indicated.

Abnormal glucose tolerance in children with cystic fibrosis: the predictive role of continuous glucose monitoring system.

UNLABELLED: A long pre-diabetic phase of abnormal glucose tolerance is described in subjects with cystic fibrosis (CF) since childhood. OBJECTIVE: The aims of the study were to compare oral glucose tolerance test (OGTT) and continuous glucose monitoring system (CGMS) in the diagnosis of altered glucose metabolism, and to longitudinally evaluate the role of CGMS in predicting glucose metabolism deterioration in children with CF. METHODS: Seventeen children with CF and 14 controls were enrolled (mean age 13.3+/-3.0 years). All subjects underwent OGTT and CGMS registration. On the basis of OGTT, children were classified as normal glucose tolerance, impaired glucose tolerance (IGT), IGT plus at least one glucose value above 200 mg/dl at intermediate OGTT points (IGT+200) and CF-related diabetes (CFRD). HbA1c, glucose area under the curve, insulin sensitivity, and insulinogenic and disposition indexes were also considered. Subjects with CF underwent another OGTT after 2.5 years. RESULTS: Baseline OGTT revealed 3/17 (7.6%) children with CF with at least one glucose value above 200 mg/dl (1 CFRD and 2 IGT+200), while CGMS revealed 6/17 (35.3%) children with glucose excursions above 200 mg/dl (P=0.010). None of the controls showed glucose over 200 mg/dl either at OGTT or at CGMS. At the 2.5-year follow-up OGTT, all the six subjects who had diabetic glucose excursion (i.e. >200 mg/dl) at baseline CGMS presented IGT+200 or CFRD. In logistic regression analysis, CGMS diabetic excursion was the strongest predictor of IGT+200 and CFRD (P<0.001). CONCLUSIONS: CGMS could be a useful tool to predict glucose metabolism derangements in children affected by CF.

Glucose tolerance status in 510 children and adolescents attending an obesity clinic in Central Italy.

UNLABELLED: Childhood obesity is epidemic in developed countries and is accompanied by an increase in the prevalence of type 2 diabetes (T2DM). AIMS: Establish prevalence of glucose metabolism alterations in a large sample of overweight/obese children and adolescents from Central Italy. METHODS: The study group included 510 overweight/obese subjects (3-18 yr). Oral glucose tolerance test (OGTT) was performed with glucose and insulin determination. Homeostatic model assessment of insulin resistance (HOMA-IR) and insulin sensitivity index (ISI) were derived from fasting and OGTT measurements. Beta-cell function was estimated by insulinogenic index. Fat mass was measured by dual-energy x-ray absorptiometry. RESULTS: Glucose metabolism alterations were detected in 12.4% of patients. Impaired glucose tolerance (IGT) was the most frequent alteration (11.2%), with a higher prevalence in adolescents than in children (14.8 vs. 4.1%, p < 0.001); silent T2DM was identified in two adolescents (0.4%). HOMA-IR and glucose-stimulated insulin levels were higher in patients with IGT than individuals with normal glucose tolerance (HOMA-IR = 4.4 +/- 2.5 vs. 3.4 +/- 2.3, p = 0.001). Fat mass percentage and insulinogenic index were not different between the two groups. In multivariate analysis, age, fasting glucose, and insulin resistance influenced independently plasma glucose at 120 min of OGTT. Individuals with combined impaired fasting glucose/IGT (IFG/IGT) and T2DM were older and had reduced plasma insulin values at OGTT when compared to patients with simple IGT. CONCLUSIONS: Glucose metabolism alterations are frequently found among children and adolescents with overweight/obesity from Central Italy. Age, fasting glucose, and insulin resistance are main predictors of IGT. We suggest the use of OGTT as a screening tool in obese European adolescents.

Obese children with low birth weight demonstrate impaired beta-cell function during oral glucose tolerance test.

OBJECTIVE: Epidemiological studies have shown an association between birth weight and future risk of type 2 diabetes, with individuals born either small or large for gestational age at increased risk. We sought to investigate the influence of birth weight on the relation between insulin sensitivity and beta-cell function in obese children. SUBJECTS AND METHODS: A total of 257 obese/overweight children (mean body mass index-sd score, 2.2 +/- 0.3), aged 11.6 +/- 2.3 yr were divided into three groups according to birth weight percentile: 44 were small for gestational age (SGA), 161 were appropriate for gestational age (AGA), and 52 were large for gestational age (LGA). Participants underwent a 3-h oral glucose tolerance test with glucose, insulin, and C-peptide measurements. Homeostasis model of assessment for insulin resistance, insulinogenic index, and disposition index were calculated to evaluate insulin sensitivity and beta-cell function. Glucose and insulin area under the curve (AUC) were also considered. One-way ANOVA was used to compare the three groups. RESULTS: SGA and LGA subjects had higher homeostasis model of assessment for insulin resistance than AGA subjects, but they diverged when oral glucose tolerance test response was considered. Indeed, SGA subjects showed higher glucose AUC and lower insulinogenic and disposition indexes. Insulin AUC was not different between groups, but when singular time points were considered, SGA subjects had lower insulin levels at 30 min and higher insulin levels at 180 min. CONCLUSIONS: SGA obese children fail to adequately compensate for their reduced insulin sensitivity, manifesting deficit in early insulin response and reduced disposition index that results in higher glucose AUC. Thus, SGA obese children show adverse metabolic outcomes compared to AGAs and LGAs.

Profile of mecasermin for the long-term treatment of growth failure in children and adolescents with severe primary IGF-1 deficiency.

Growth hormone insensitivity syndrome (GHI) or insulin-like growth factor-1 (IGF-1) deficiency (IGFD) is characterized by deficit of IGF-1 production due to alteration of response of growth hormone (GH) receptor to GH. This syndrome is due to mutation of GH receptor or IGF-1 gene and patients affected showed no response to GH therapy. The only treatment is recombinant IGF-1 (mecasermin), which has been available since 1986, but approved in the United States by the US Food and Drug Administration only in 2005 and in Europe by the European Medicines Agency in 2007. To date, few studies are available on long-term treatment with mecasermin in IGFD patients and some of them have a very small number of subjects. In this review we discuss briefly clinical features of severe primary IGFD, laboratory findings, and indications for treatment. Results of long-term therapy with rhIGF1 (mecasermin) in patients affected by severe primary IGFD and possible side effects are explained.

Sexual dimorphism of body composition and insulin sensitivity across pubertal development in obese Caucasian subjects.

Background Puberty is a period of rapid growth associated with metabolic, hormonal, and body composition changes that can influence risk factors for chronic diseases such as type 2 diabetes. Objective To evaluate body composition and insulin sensitivity (IS) modifications throughout puberty in a large group of obese Caucasian subjects. Methods Five hundred and nineteen obese subjects (4-19 years), grouped according to gender and Tanner stage (T), underwent oral glucose tolerance test. Quantitative insulin check index (QUICKI) and ISI were calculated as indexes of IS. In 309 subjects, body composition by dual-energy X-ray absorptiometry, IGF1, adiponectin, and leptin were also evaluated. Results Body composition modifications were sexually dimorphic, with girls not modifying fat and lean percentage and fat distribution (P>0.15), and boys decreasing fat percentage and increasing lean percentage and central fat depot (P<0.001) across Ts. IS decreased during mid-puberty and returned to prepubertal levels by the end of puberty. Girls showed lower IS than boys (P<0.01 and =0.03 for QUICKI and ISI respectively). In multivariate analysis factors that negatively influenced IS, independently from T or age, were total fat mass and central fat depot in girls (P<0.05 and <0.01, respectively), total fat and lean mass in boys (P<0.01). IGF1, adiponectin, and leptin were not related to pubertal IS. Conclusions In obese Caucasian subjects, further decrease of IS observed during puberty is a transient phenomenon. Factors that independently from T or age influence IS are central fat depot in girls, lean amount in boys, and total fat mass in both sexes.

Cardiovascular fitness, insulin resistance and metabolic syndrome in severely obese prepubertal Italian children.

AIM: To evaluate if insulin resistance (IR) and metabolic syndrome (MS) were associated with poor cardiovascular fitness in very obese prepubertal Italian subjects. METHODS: Children referred to the Endocrinology and Diabetes Unit of Bambino Gesù Children's Hospital underwent an OGTT with glucose and insulin assays. QUICKI, ISI and HOMA-IR were calculated. Total and HDL cholesterol, triglycerides and percentage of body fat (DEXA) were determined. Cardiovascular fitness (maximal treadmill time) was evaluated using a treadmill protocol. The MS was defined as having 3 or more of following risk factors: obesity, impaired glucose tolerance, high blood pressure, low HDL-cholesterol, high triglycerides. RESULTS: Fifty-five very obese prepubertal Italian children were enrolled in the study. Unadjusted correlation revealed maximal treadmill time negatively related to fasting insulin (r = -0.53, p < 0.0001) and HOMA-IR (r = -0.57, p < 0.0001) and positively to QUICKI (r = 0.51, p < 0.0001) and ISI (r = 0.46, p = 0.0035). These relationships remained significant when in multivariate analysis age, gender, BMI SD and body composition were accounted for (all p < 0.01). The presence of the MS was independently associated with maximal treadmill time. CONCLUSION: Poorcardiovascular fitness, IR and MS were independently related, suggesting that the relationship between fitness and insulin action develops early in life.

Treatment of benign cold thyroid nodules: a randomized clinical trial of percutaneous laser ablation versus levothyroxine therapy or follow-up.

AIM OF THE STUDY: To compare clinical and ultrasound (US) changes induced in cold thyroid nodules by US-guided percutaneous laser ablation (PLA) versus follow-up or levothyroxine (LT4) suppressive therapy. METHODS: 62 patients randomly assigned to a single PLA (Group 1), LT4 (Group 2), or follow-up (Group 3). Entry criteria: euthyroid patients with a solid thyroid nodule >5 mL and benign cytological findings. TREATMENT: Group 1: PLA was performed with a 1.064 mum neodymium yttrium-aluminum-garnet laser with output power of 3 W for 10 minutes; Group 2: the LT4 dose was adjusted to induce thyrotropin suppression; Group 3: no treatment. RESULTS: In Group 1 a significant nodule reduction was found 6 and 12 months after PLA (delta volume: -42.7 +/- 13.6%; p = 0.001). A reduction >50% was found in 33.3% of cases. In Group 2 a nonsignificant nodule shrinkage was observed. A nonsignificant volume increase was observed in Group 3. Improvement of local symptoms was registered in 81.2% of patients in Group 1 vs. 13.3% in Group 2 and 0.0% in Group 3 ( p = 0.001). No complications were noted. CONCLUSIONS: A single PLA induced significant volume reduction and improvement of local symptoms. PLA was more effective than LT4. Follow-up was associated with nodule growth and progression of local symptoms. PLA should be considered a potential mini-invasive alternative to surgery in symptomatic patients with benign cold thyroid nodules.