[Show abstract][Hide abstract] ABSTRACT: 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.
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).
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).
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.
PLoS ONE 04/2014; 9(4):e92995. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Small for gestational age (SGA) refers to a child whose weight and, or, length at birth is less than a -2 standard deviation score (SDS) (1). Subjects born SGA have an increased risk of developing permanent metabolic changes as a result of intrauterine programming, leading to increased cardiometabolic risk in adulthood, including hypertension, excess abdominal fat deposition and type 2 diabetes (2). An appropriate lifestyle, based on a balanced diet and adequate physical activity, is the primary preventive intervention for reducing long-term cardiometabolic risk. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
Hormone Research in Paediatrics 07/2013; · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Hormone Research in Paediatrics 06/2013; · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
Hormone Research in Paediatrics 07/2012; 78(2):100-5. · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Benefit of fitness on children with type 1 diabetes mellitus (T1DM) is still debated. Aim: To evaluate the influence of physical activity on metabolic balance and exercise tolerance in prepubertal children affected by T1DM.
We analyzed 35 pre-/peripubertal T1DM children and 31 matched controls using an activity monitor (SenseWear Armbad) and physical activity questionnaire (PAQ) to assess energy expenditure (EE), total and active, sedentary and physical activities (h/day and Mets = metabolic equivalents). The maximal cardiopulmonary exercise test (CPET) was also performed.
Total physical activities and total and active EE (>3 Mets) resulted higher in controls than in T1DM patients and self-reported perception of physical and sedentary activities was altered in T1DM children as well in controls and were different from the measured data. No differences were found in CPET parameters with the exception of a higher maximal blood pressure in T1DM children. In multivariate analysis HbA1c negatively correlated with VO(2).
Prepubertal T1DM children seem to have a lower level of physical activity and EE and a probable altered feeling of physical and sedentary activities. On the other hand, T1DM children do not show any alteration of cardiovascular performance, although glycemic control (HbA1c) may play a role in cardiovascular performance.
Hormone Research in Paediatrics 06/2012; 78(1):1-7. · 1.55 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of our study was to evaluate the physical and sedentary activities and energy expenditure (EE) in a group of children affected by non-alcoholic fatty liver disease (NAFLD), compared with normal and obese subjects, using a physical activity questionnaire (PAQ) and a SenseWear armband (SWA).
Forty NAFLD (10 females), 41 lean (NRM; 11 females) and 30 obese (OB; 10 females), age- and pubertal stage-matched, children were included.
Sedentary activity (PAQ) was similar in NAFLD and NRM but less in OB, while SWA showed that NAFLD spent less time in physical activity and more in sedentary activities compared with NRM, but not with OB. Insulin sensitivity index result is related to active EE (cal kg(-1) d(-1) ) in NAFLD, while homeostatic model assessment index result was negatively related to total EE in OB.
Regular physical activity must be encouraged in all obese children affected by NAFLD or not, and SWA might be a possible valid tool for evaluating actual EE.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: The aim of our study was to evaluate the physical and sedentary activities and energy expenditure (EE) in a group of children affected by non-alcoholic fatty liver disease (NAFLD), compared with normal and obese subjects, using a physical activity questionnaire (PAQ) and a SenseWear armband (SWA).
METHODS: Forty NAFLD (10 females), 41 lean (NRM; 11 females) and 30 obese (OB; 10 females), age- and pubertal stage-matched, children were included.
RESULTS: Sedentary activity (PAQ) was similar in NAFLD and NRM but less in OB, while SWA showed that NAFLD spent less time in physical activity and more in sedentary activities compared with NRM, but not with OB. Insulin sensitivity index result is related to active EE (cal kg(-1) d(-1) ) in NAFLD, while homeostatic model assessment index result was negatively related to total EE in OB.
CONCLUSIONS: Regular physical activity must be encouraged in all obese children affected by NAFLD or not, and SWA might be a possible valid tool for evaluating actual EE.
International Journal of Pediatric Obesity 04/2012; · 3.03 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Adults with normal glucose tolerance (NGT) but exaggerated plasma glucose excursion at 1 h (1HPG) following the oral glucose tolerance test (OGTT) have significantly higher risk of developing impaired glucose tolerance (IGT) or diabetes. Aim of the study will be to characterize the metabolic phenotype of NGT obese youth according to values of 1HPG. To accomplish this aim, obese patients (N = 1,454; 761 men; 79 IGT; BMI z-score 2.56 ± 0.16 SDS; age 11 ± 0.7 years) from two data sets were analyzed. In all patients, empirical parameters of insulin metabolism were calculated in fasting condition and following an OGTT (1.75 mg of glucose per kilogram/body weight). Receiver-operating characteristic (ROC) analysis was performed in the first group (training set, N = 920) to establish the cutoff value of 1HPG best identifying IGT. The second set (validation set, N = 534) served to verify the goodness of the model and the identified cutoff values. 1HPG ≥ 132.5 mg/dl identified IGT with 80.8% sensitivity and 74.3% specificity in the training set (AUC 0.855, 95% CI 0.808-0.902, p < 0.0001), and 70.3% sensitivity and 80% specificity in the validation set (AUC 0.81, 95% CI 0.713-0.907, p < 0.0001), respectively. NGT patients with 1HPG ≥ 132.5 mg/dl had a metabolic phenotype (triglycerides, insulin action, and secretion) that was in between those of NGT patients with 1HPG below the threshold and IGT patients (p < 0.0001 for all the comparisons). 1HPG ≥ 132.5 mg/dl seems to be associated with increased metabolic risk in obese youth, identifying patients with lower insulin sensitivity, early secretion, and higher total insulin secretion than in obese mates with lower 1HPG.
[Show abstract][Hide abstract] ABSTRACT: Metabolic characteristics and rate of progression to overt Type 2 diabetes (T2D) in low-risk European obese children are not well documented. Aim of the study was to investigate differences in insulin sensitivity and secretion in Italian obese children and youngsters with pre-diabetes.
Ninety-six obese children and youngsters with pre-diabetes, pair-matched with individuals with normal glucose tolerance (NGT) were included in the present study. Participants were screened by oral glucose tolerance. Pre-diabetes was classified as impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and combined IFG-IGT. Homeostasis model assessment of insulin resistance (HOMA-IR), 2-h insulin, insulin sensitivity index (ISI) and disposition index (DI) were calculated to estimate fasting, peripheral and whole body insulin sensitivity and capacity of pancreatic islets to compensate for lower insulin sensitivity, respectively. One-way analysis of variance was used to compare groups.
Eleven subjects had IFG (11.5%), 79 IGT (82.3%), 6 combined IFG-IGT (6.3%). Individuals with IFG showed the highest HOMA-IR (p=0.0007), those with IGT the highest 2-h insulin (p<0.0001), those with IFG-IGT the lowest ISI (p<0.0001), with severely reduced DI (p=0.0003). Compared with NGT, DI was 60% lower in those with IFG-IGT.
IFG is linked primarily to fasting insulin resistance, IGT to peripheral insulin resistance. IFG-IGT is hallmarked by reduced whole body insulin sensitivity and an additional severe defect in DI. Further longitudinal studies are needed to understand whether the different categories of pre-diabetes in European obese adolescents represent real pre-diabetic alterations.
Journal of endocrinological investigation 06/2011; 34(9):e275-80. · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To investigate whether body mass index (BMI) and body composition can affect peak bone mass in a population of obese (OB) (BMI SDS>2.0) and normal weight (NORM) (BMI-SD score <2.0) pubertal subjects (Tanner stage T3 to T5).
151 subjects (81 OB, age 14.5±2.4 yr) were analyzed using dual-X-ray absorbiometry technique to study Lumbar and whole body bone mineral density (BMD) (areal, normalized for height) and Z-score, lean mass (LM) and lean/fat ratio.
As a whole group, OB males did not show any significant difference in bone parameters vs NORM, while OB females showed higher bone density parameters (p<0.05). When grouped according to T, while OB males showed higher bone density at T3-4 stage (p<0.01), and lower at T5 (p<0.01) compared to NORM, OB females showed a tendency through increased BMD at T3-4 and T5 although statistically different only at T5. BMD was independently correlated to LM, lean/fat ratio, and testosterone in NORM males and, at lower level, in OB males, while to LM in NORM females and only to age in OB females.
Our data seem to confirm the possible negative influence of obesity on bone density in boys, a possible explanation could be an unfavorable body composition during sexual maturation that seems not to affect bone development in adolescents girls.
Journal of endocrinological investigation 04/2011; 34(4):e86-91. · 1.65 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
International journal of hypertension. 01/2011; 2011:257168.
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
Cardiology in the Young 11/2010; 21(1):89-93. · 0.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The results of studies on the genetics of complex traits need to be replicated and to reach robust statistical significance before they can be considered as established. We here tried to replicate the previously reported association between the TRIB3 Q84R polymorphism (rs2295490) and glucose homeostasis.
Three samples of Europeans with fasting glucose <7.0 mmol/l were studied. In sample 1 (n=791), the association between TRIB3 Q84R and impaired glucose regulation (IGR; defined as impaired fasting glucose and/or impaired glucose tolerance and/or type 2 diabetes by OGTT) and insulin sensitivity (ISI), and its interplay with early-phase insulin secretion (i.e. disposition index [DI]) were analysed. Sample 2 (n=374) and sample 3 (n=394) were used to replicate the association with IGR and insulin sensitivity (by glucose clamp), respectively. Genotyping was performed by TaqMan allele discrimination.
R84 carriers were at higher risk of IGR: OR for the additive model 1.54, p=0.004, and 1.63, p=0.027, in samples 1 and 2, respectively. In sample 1, both ISI (p=0.005) and DI (p=0.043) were progressively lower from QQ to QR and RR individuals. A 'triangulation approach' indicated that the association with IGR was mostly mediated by DI rather than by ISI changes (i.e. being the expected ORs 1.51 and 1.25, respectively). In sample 3, glucose disposal was 38.8+/-17.7, 33.8+/-14.4, and 31.6+/-13.3 micromol min(-1)kg(-1), p=0.022, in QQ, QR and RR individuals, respectively.
Our data confirm that the TRIB3 R84 variant affects glucose homeostasis and suggest this effect is due to an alteration of the interplay between insulin sensitivity and secretion.
[Show abstract][Hide abstract] ABSTRACT: A long pre-diabetic phase of abnormal glucose tolerance is described in subjects with cystic fibrosis (CF) since childhood.
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.
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.
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).
CGMS could be a useful tool to predict glucose metabolism derangements in children affected by CF.
European Journal of Endocrinology 04/2010; 162(4):705-10. · 3.69 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
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.
The Journal of Clinical Endocrinology and Metabolism 10/2009; 94(11):4448-52. · 6.31 Impact Factor