Multicentric Italian case-control study on 25OH vitamin D levels in children and adolescents with Prader-Willi syndrome.

PURPOSE: 25OHD levels in patients with Prader-Willi Syndrome (PWS), the most frequent cause of genetic obesity with a peculiar fat mass distribution, are still debated. Insulin resistance (IR), Body Mass Index-SDS (BMI-SDS), Growth Hormone Therapy (GHT), and puberty onset seem to interact with 25OHD levels. The objectives of the study are: (1) To analyze 25OHD levels in pediatric PWS patients in comparison with a control group (CNT) (2) To evaluate a possible correlation between BMI-SDS, HOMA-IR, puberty, GHT, and 25OHD levels. METHODS: This is a retrospective case-control, multicenter study. Data were collected among 8 different Italian Hospitals (outpatient clinics), over a period of four years (2016-2020). We included 192 genetically confirmed PWS and 192 CNT patients, aged 3-18 years, matched 1:1 for age, gender, BMI-SDS, Tanner stage, sun exposure, and month of recruitment. RESULTS: No statistically significant differences in 25OHD levels were observed between the PWS population and the CNT (PWS 24.0 ng/mL vs CNT 22.5 ng/mL, p > 0.05), OR = 0.89 (95% CI 0.58-1.35). We observed a slight, although non-significant, reduction in 25OHD levels comparing NW and OB populations. HOMA-IR, puberty onset, genotype and GHT (previous or ongoing) did not show statistically significant correlation with 25OHD levels. CONCLUSIONS: Our findings could be useful for clinicians to optimize the therapeutic management as well as to increase awareness of PWS.

Screening for hypertension in young people with obesity: Feasibility in the real life.

BACKGROUND AND AIM: Screening for pediatric hypertension (HTN) is based on several measurements of blood pressure (BP) in different visits. We aimed to assess its feasibility in outpatient youths with overweight/obesity (OW/OB) in terms of adherence to two-repeated measurements of BP and to show the features of youths who missed the follow-up and the predictive role of clinical and/or anamnestic features on confirmed HTN. METHODS AND RESULTS: Six hundred, eighty-eight youths (9-17 years) with OW/OB, consecutively recruited, underwent a first measurement of BP. Those exhibiting BP levels within the hypertensive range were invited to repeat a second measurement within 1-2 weeks. Confirmed HTN was diagnosed when BP in the hypertensive range was confirmed at the second measurement. At entry, 174 youths (25.1%) were classified as hypertensive. At the second visit, 66 youths (37.9%) were lost to follow-up. In the remaining 108 participants, HTN was confirmed in 59, so that the prevalence of confirmed HTN was 9.5% in the overall sample; it was higher in adolescents than children (15.9% vs 6.8%, P = 0.001). HTN at first visit showed the best sensitivity (100%) and a good specificity (91%) for confirmed HTN. The association of HTN at first visit plus familial HTN showed high specificity (98%) and positive predictive value of 70%. CONCLUSION: The high drop-out rate confirms the real difficulty to obtain a complete diagnostic follow up in the obese population. Information about family history of HTN may assist pediatricians in identifying those children who are at higher risk of confirmed HTN.

Phenotypes of prediabetes and metabolic risk in Caucasian youths with overweight or obesity.

PURPOSE: To assess the prevalence of pre-diabetes phenotypes, i.e., impaired fasting glucose (IFG), impaired glucose tolerance (IGT), increased HbA1c (IA1c), and their association with metabolic profile and atherogenic lipid profile in youths with overweight/obesity (OW/OB). METHODS: This cross-sectional study analyzed data of 1549 youths (5-18 years) with OW/OB followed in nine Italian centers between 2016 and 2020. Fasting and post-load measurements of glucose, insulin, and HbA1c were available. Insulin resistance (IR) was estimated by HOMA-IR and insulin sensitivity (IS) by reciprocal of fasting insulin. The atherogenic lipid profile was assessed by triglycerides-to-HDL ratio or cholesterol-to-HDL ratio. Insulinogenic index was available in 939 youths, in whom the disposition index was calculated. RESULTS: The prevalence of overall pre-diabetes, IFG, IGT and IA1c was 27.6%, 10.2%, 8% and 16.3%, respectively. Analyzing each isolated phenotype, IGT exhibited two- to three-fold higher odds ratio of family history of diabetes, and worse metabolic and atherogenic lipid profile vs normoglycemic youths; IFG was associated only with IR, while IA1c showed a metabolic and atherogenic lipid profile intermediate between IGT and IFG. CONCLUSION: Prevalence of pre-diabetes was high and IA1c was the most prevalent phenotype in Italian youths with OW/OB. The IGT phenotype showed the worst metabolic and atherogenic lipid profile, followed by IA1c. More studies are needed to assess whether HbA1c may help improving the prediction of diabetes.

Stimulated GH levels during the transition phase in Prader-Willi syndrome.

PURPOSE: Early institution of GH therapy in children with Prader-Willi syndrome (PWS) yields beneficial effects on their phenotype and is associated with a persistent improvement of body composition, both in the transition age and in adulthood. Reports from GH stimulation testing in PWS adults, however, suggest that GH deficiency (GHD) is not a universal feature of the syndrome, and the current Consensus Guidelines suggest to perform a reassessment of persistent GHD so as to continue GH therapy after reaching adult height. Few data about GH responsiveness to stimulation testing throughout the transitional period in PWS are available to date. Thus, we investigated the prevalence of GHD in a large cohort of patients with PWS during the transition phase. PATIENTS AND METHODS: One hundred forty-one PWS patients, 72 females and 69 males, aged 15.4-24.9 years, were evaluated by dynamic testing with growth hormone-releasing hormone (GHRH) plus arginine (GHRH + ARG). To define GHD, both BMI-dependent and BMI-independent diagnostic cut-off limits were considered. RESULTS: According to BMI-dependent criteria, 10.7% of normal weight (NW), 18.5% of overweight and 22.1% of obese PWS maintained a status of GHD. Similar results were obtained by adopting a cut-off limit specific for the adult age (26.2%), as well as criteria for the transition phase in NW subjects (25%). CONCLUSION: Our study shows that about 20% of patients with PWS fulfilled the criteria for GHD during the transitional age, suggesting the need of an integrated analysis of GH/IGF-I axis, in the context of the general clinical picture and other endocrine abnormalities, in all subjects after attainment of final stature.

High uric acid, reduced glomerular filtration rate and non-alcoholic fatty liver in young people with obesity.

OBJECTIVE: To evaluate the association between high uric acid (UA), reduced estimated glomerular filtration rate (eGFR), and non-alcoholic fatty liver disease (NAFLD) in outpatient children and adolescents with overweight (OW) or obesity (OB). METHODS: Anthropometric, biochemical, hepatic ultrasound and eGFR data were available from 2565 young people with OW/OB (age 5-18 years). eGFR was calculated using the Schwartz's bedside formula and reduced eGFR (ReGFR+) was defined by a value < 90 mL/min/1.73 m2. High UA was defined as ≥ 75th percentile by sex in children and adolescents. RESULTS: The population was stratified in four categories: (1) normal eGFR and absence of NAFLD (ReGFR-/NAFLD-) (n = 1,236); (2) ReGFR+ and absence of NAFLD (ReGFR+/NAFLD- (n = 155); (3) normal eGFR and presence of NAFLD (ReGFR-/NAFLD+) (n = 1019); (4) presence of both conditions (ReGFR+/NAFLD+) (n = 155). Proportions of youth with high UA across the four categories were 17%, 30%, 33% and 46%, respectively (P < 0.0001). Young people with high levels of UA had odds ratio (95% CI) of 2.11 (1.43-3.11) for ReGFR+; 2.82 (2.26-3.45) for NAFLD+; and 5.04 (3.45-7.39) for both conditions (P < 0.0001 for all), independently of major confounders. CONCLUSIONS: High levels of UA were independently associated with ReGFR, NAFLD and the combination of both conditions in young people with OW/OB. The strength of this association was the highest in cases presenting both reduced eGFR and NAFLD. UA may serve as marker to identify patients at risk for these conditions.

Preclinical signs of liver and cardiac damage in youth with metabolically healthy obese phenotype.

BACKGROUND AND AIMS: We aimed to evaluate whether the metabolically healthy obese (MHO) phenotype was associated with hepatic steatosis (HS) or left ventricular hypertrophy (LVH) in young people with overweight (OW), obesity (OB) and morbid obesity (MOB) and whether the prevalence of these comorbidities was affected by OB severity. METHODS AND RESULTS: An abdominal ultrasound was performed in 1769 children and adolescents, mean age 10.6 years (range 5-18) with MHO phenotype, defined as the absence of traditional cardiometabolic risk factors, in order to identify HS. In a subsample of 177 youth the presence of LVH, defined by 95th percentile of LV mass/h2.7 for age and gender, was also analyzed. The prevalence of HS increased from 23.0% in OW to 27.8% in OB and 45.1% in MOB (P < 0.0001). The proportion of LVH increased from 36.8% in OW to 57.9% in OB and 54.5% in MOB (P < 0.05). As compared with OW, the odds ratio (95% CI) for HS was 2.18 (1.56-3.05), P < 0.0001) in OB and 6.20 (4.26-9.03), P < 0.0001) in MOB, independently of confounding factors. The odds ratio for LVH was 2.46 (1.20-5.06), P < 0.025) in OB and 2.79 (1.18-6.61), P < 0.025) in MOB, as compared with OW. CONCLUSION: In spite of the absence of traditional cardiometabolic risk factors, the prevalence of HS and LVH progressively increased across BMI categories. MHO phenotype does not represent a "benign" condition in youth.

A new index to simplify the screening of hypertension in overweight or obese youth.

BACKGROUND AND AIMS: Hypertension (HTH) is a frequent complication in pediatric obesity. To simplify the screening of HTH in overweight/obese (Ow/Ob) youth, we compared the performance of a new index (High Blood Pressure index, HBPi) with respect to the standard criteria of the IV Report [systolic BP (SBP) and/or diastolic BP (DBP) ≥95th percentile for age, gender and height]. We also compared the performance of HBPi with other simplified indices such as the BP/height ratio and the absolute height-specific BP thresholds. Ten pediatrics' outpatient centers participating in the "CARdiometabolic risk factors in ITALY study" provided medical records of 4225 Ow/Ob children and adolescents (age 6-16 years). METHODS AND RESULTS: Centers were divided into two groups: training set (TS) (n = 2204 participants) and validation set (VS) (n = 2021 participants). The simplified HBPi (mmHg) was: (SBP/2 + DBP/10) - age + (1 × female gender). In the TS, a HBPi value ≥57 mmHg in both children and adolescents had high sensitivity (0.89), specificity (0.97), positive (0.89) and negative (0.97) predictive values in classifying youth at high risk of HTN compared with the IV Report. In the VS, the HBPi showed a better performance than high levels of BP/height ratio and height-specific BP thresholds in classifying individuals at risk of HTN: area under curves 0.95 (0.93-0.96), 0.80 (0.78-0.82), 0.76 (0.74-0.79), respectively; specificities 0.95 (0.94-0.96), 0.69 (0.67-0.72), 0.60 (0.57-0.62), respectively. CONCLUSIONS: HBPi, combining SBP and DBP, gender and age, may help pediatricians to implement HTN screening in Ow/Ob youth.

Impaired fasting glucose and impaired glucose tolerance in children and adolescents with overweight/obesity.

OBJECTIVE: To investigate in a large sample of overweight/obese (OW/OB) children and adolescents the prevalence of prediabetic phenotypes such as impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), and to assess their association with cardiometabolic risk (CMR) factors including hepatic steatosis (HS). METHODS: Population data were obtained from the CARdiometabolic risk factors in children and adolescents in ITALY study. Between 2003 and 2013, 3088 youths (972 children and 2116 adolescents) received oral glucose tolerance test (OGTT) and were included in the study. In 798 individuals, abdominal ultrasound for identification of HS was available. RESULTS: The prevalence of IFG (3.2 vs. 3.3%) and IGT (4.6 vs. 5.0%) was similar between children and adolescents. Children with isolated IGT had a 2-11 fold increased risk of high LDL-C, non-HDL-C, Tg/HDL-C ratio, and low insulin sensitivity, when compared to those with normal glucose tolerance (NGT). No significant association of IFG with any CMR factor was found in children. Among adolescents, IGT subjects, and to a lesser extent those with IFG, showed a worse CMR profile compared to NGT subgroup. In the overall sample, IGT phenotype showed a twofold increased risk of HS compared to NGT subgroup. CONCLUSIONS: Our study shows an unexpected similar prevalence of IFG and IGT between children and adolescents with overweight/obesity. The IGT phenotype was associated with a worse CMR profile in both children and adolescents. Phenotyping prediabetes conditions by OGTT should be done as part of prediction and prevention of cardiometabolic diseases in OW/OB youth since early childhood.

White blood cell count may identify abnormal cardiometabolic phenotype and preclinical organ damage in overweight/obese children.

BACKGROUND AND AIMS: Subclinical inflammation is a central component of cardiometabolic disease risk in obese subjects. The aim of the study was to evaluate whether the white blood cell count (WBCc) may help to identify an abnormal cardiometabolic phenotype in overweight (Ow) or obese (Ob) children. METHODS AND RESULTS: A cross-sectional sample of 2835 Ow/Ob children and adolescents (age 6-18 years) was recruited from 10 Italian centers for the care of obesity. Anthropometric and biochemical variables were assessed in the overall sample. Waist to height ratio (WhtR), alanine aminotransferase (ALT), lipids, 2 h post-load plasma glucose (2hPG), left ventricular (LV) geometry and carotid intima-media thickness (cIMT) were assessed in 2128, 2300, 1834, 535 and 315 children, respectively. Insulin resistance and whole body insulin sensitivity index (WBISI) were analyzed using homeostatic model assessment (HOMA-IR) and Matsuda's test. Groups divided in quartiles of WBCc significantly differed for body mass index, WhtR, 2hPG, HOMA-IR, WBISI, lipids, ALT, cIMT, LV mass and relative wall thickness. Children with high WBCc (≥8700 cell/mm(3)) showed a 1.3-2.5 fold increased probability of having high normal 2hPG, high ALT, high cIMT, or LV remodeling/concentric LV hypertrophy, after adjustment for age, gender, pubertal status, BMI and centers. CONCLUSIONS: This study shows that WBCc is associated with early derangements of glucose metabolism and preclinical signs of liver, vascular and cardiac damage. The WBCc may be an effective and low-cost tool for identifying Ow and Ob children at the greatest risk of potential complications.

Adherence in children with growth hormone deficiency treated with r-hGH and the easypod™ device.

PURPOSE: Poor adherence to recombinant human growth hormone (r-hGH) therapy is associated with reduced growth velocity in children with growth hormone deficiency (GHD). This twelve-month observational study was to assess adherence in r-hGH patients treated with the easypod™, an electronic, fully automated injection device designed to track the time, date and dose administered. METHODS: Ninety-seven prepubertal patients receiving r-hGH therapy were included in the study from ten Italian clinical sites and 88 completed the study. To avoid possible confounding effects, only GHD patients (79/88; 89.7 % of the overall study population) were considered in the final analysis. The primary endpoint-adherence to treatment-was calculated as the proportion of injections correctly administered during the observational period out of the expected total number of injections. The relevant information, tracked by the easypod™, was collected at months 6 (V1) and 12 (V2) after baseline (V0). At study termination, adherence data were partially available from 16 patients and fully available from 53 patients. As secondary endpoints, serum IGF-1 levels, fasting serum glucose and insulin levels and key anthropometric characteristics (height, waist circumference and BMI) were also determined. RESULTS: The easypod™ data showed that 56.7 % of the patients were considered to be fully (≥92 %) adherent to their treatment throughout the period V0-V2. Treatment improved stature, significantly increased IGF-1 and produced a non-significant increase in blood glucose and insulin levels. CONCLUSIONS: The injection-recording system and other characteristics of easypod™ could enhance the ability of physicians to monitor adherence to r-hGH treatment.

Comparison of non-HDL-cholesterol versus triglycerides-to-HDL-cholesterol ratio in relation to cardiometabolic risk factors and preclinical organ damage in overweight/obese children: the CARITALY study.

BACKGROUND AND AIMS: Lipid ratios to estimate atherosclerotic disease risk in overweight/obese children are receiving great attention. We aimed to compare the performance of non-high-density lipoprotein-cholesterol (HDL-C) versus triglycerides-to-HDL-C ratio (Tg/HDL-C) in identifying cardiometabolic risk factors (CMRFs) or preclinical signs of organ damage in outpatient Italian overweight/obese children. METHODS AND RESULTS: In this retrospective, cross-sectional study, 5505 children (age 5-18 years) were recruited from 10 Italian centers for the care of obesity, of which 4417 (78%) showed obesity or morbid obesity. Anthropometric, biochemical, and blood pressure variables were analyzed in all children. Liver ultrasound scan, carotid artery ultrasound, and echocardiography were performed in 1257, 601, and 252 children, respectively. The entire cohort was divided based on the 75th percentile of non-HDL-C (≥130 mg/dl) or Tg/HDL-C ratio (≥2.2). The odds ratio for insulin resistance, high blood pressure, metabolic syndrome, presence of liver steatosis, increased levels of carotid intima-media thickness (cIMT) and concentric left ventricular hypertrophy (cLVH) was higher in children with high levels of Tg/HDL-C with respect to children with high levels of non-HDL-C. CONCLUSIONS: In an outpatient setting of overweight/obese children, Tg/HDL-C ratio discriminated better than non-HDL-C children with CMRFs or preclinical signs of liver steatosis, and increased cIMT and cLVH.

Four novel UCP3 gene variants associated with childhood obesity: effect on fatty acid oxidation and on prevention of triglyceride storage.

OBJECTIVE: The objective of the study was to look for uncoupling protein 3 (UCP3) gene variants in early-onset severe childhood obesity and to determine their effect on long-chain fatty acid oxidation and triglyceride storage. METHODS AND RESULTS: We identified four novel mutations in the UCP3 gene (V56M, A111V, V192I and Q252X) in 200 children with severe, early-onset obesity (body mass index-standard deviation score >2.5; onset: <4 years) living in Southern Italy. We evaluated the role of wild-type (wt) and mutant UCP3 proteins in palmitate oxidation and in triglyceride storage in human embryonic kidney cells (HEK293). Palmitate oxidation was ∼60% lower (P<0.05; P<0.01) and triglyceride storage was higher in HEK293 cells expressing the four UCP3 mutants than in cells expressing wt UCP3. Moreover, mutants V56M and Q252X exerted a dominant-negative effect on wt protein activity (P<0.01 and P<0.05, respectively). Telmisartan, an angiotensin II receptor antagonist used in the management of hypertension, significantly (P<0.05) increased palmitate oxidation in HEK293 cells expressing wt and mutant proteins (P<0.05; P<0.01), including the dominant-negative mutants. CONCLUSIONS: These data indicate that protein UCP3 affects long-chain fatty acid metabolism and can prevent cytosolic triglyceride storage. Our results also suggest that telmisartan, which increases fatty acid oxidation in rat skeletal muscle, also improves UCP3 wt and mutant protein activity, including the dominant-negative UCP3 mutants.

Metabolic changes after a hypocaloric, low-glycemic-index diet in obese children.

BACKGROUND: A low glycemic index (LGI) diet has been proposed as a treatment for obesity in adults; few studies have evaluated LGI diets in obese children. AIM: The purpose of the study was to compare the effects of two diets, with similar energy intakes, but different glycemic indexes in a pediatric outpatient setting. SUBJECTS AND METHODS: A parallel- group, randomized controlled trial was conducted, and 22 obese outpatient children with a body mass index (BMI) Z-score >2 (11 females and 11 males, BMI 28.9±2.9 kg/m²) were included in the study. Patients were randomly allocated to a hypocaloric LGI (GI:60), or to a hypocaloric high glycemic index (HGI) diet (GI:90). The LGI and HGI diets were almost equivalent for macronutrient composition. Anthropometric and biochemical parameters were measured at baseline and after 6 months. RESULTS: In both groups there were significant decreases in BMI, BMI Z-score, blood pressure, and high-sensitivity C-reactive protein. Only LGI diets produced a significant decrease in waist circumference and homeostasis model assessment. Analysis of variance demonstrated that the BMI Z-score decrease from baseline values was significantly greater after the LGI diet than after the HGI diet [-0.20 (95% confidence interval (CI) -0.29 to -0.10) vs -0.34 (95%CI -0.43 to -0.24)], mean difference between groups -0.14 (95%CI -0.27 to -0.01), p<0.05). Changes in triglyceride concentrations were significantly lower in LGI as compared to HGI diet (p<0.05). CONCLUSIONS: This study demonstrates that a hypocaloric LGI diet has beneficial metabolic effects in comparison to a hypocaloric HGI diet in obese children.

Carotid artery wall hypertrophy in children with metabolic syndrome.

Preclinical vascular changes (increased stiffness and/or wall thickness) have been observed in children with known metabolic risk factors. Aim of the present study was to evaluate different carotid parameters, representative of vascular health, in children with and without metabolic syndrome (MS). We studied 38 children with MS (mean age 9.6+/-2.6 years; range 6-14 years) and 45 healthy age-matched subjects. Children who met three or more of the following criteria qualified as having the MS: fasting glucose >110 mg dl(-1), fasting triglyceride concentration >100 mg dl(-1), fasting high-density lipoprotein cholesterol concentration <50 mg dl(-1) for females or <45 mg dl(-1) for the males, waist circumference >75th percentile for age and gender and systolic or diastolic blood pressure >90th percentile for age, gender and height. Carotid B-mode ultrasound examinations were performed and intima-media thickness and diameters were measured in all subjects. Arterial geometry was further characterized by calculation of carotid cross-sectional area. Carotid intima-media thickness and lumen diameters were increased in children with MS as compared to children without MS. Moreover, carotid cross-sectional area was significantly higher in the group of children with MS 9.83+/-1.86 mm(2) [mean+/-s.d.] compared with the control group: 7.77+/-1.72 mm(2), P<0.001, even after adjustment for age, gender and height. Carotid hypertrophy is already detectable in children with MS. High-resolution B-mode ultrasound could provide a valuable tool for the cardiovascular risk stratification of children.

[Health consequences of obesity in children and adolescents]. / Conseguenze dell'obesità sulla salute del bambino e dell' adolescente.

Obesity in childhood is associated with the presence of complications that can undermine health immediately or in the long term. Several conditions, such as pulmonary or orthopedic complications are strictly associated with the severity of overweight, since they are directly associated to the mechanic stress of fat tissue on the airways or on the bones. Other conditions, such as metabolic or liver complications, although increasing with the extent of overweight, are associated with insulin resistance, which can be modulated by different other factors (ethnicity, genetics, fat distribution) and can occur in overweight children as well. No less important are psychological correlates, such as depression and stigma, which can seriously affect the health related quality of life. Pediatric services for the care of childhood obesity need to be able to screen overweight and obese children for the presence of physical and psychological complications, which can be still reversed by weight loss. This article provides pediatricians a comprehensive update on the main complications in obese children and adolescents and their treatment.

[Management of children and adolescents with severe obesity]. / Il percorsi terapeutico del bambino e dell' adolescente con obesità grave.

Obesity is a complex public health issue. Recent data indicate the increasing prevalence and severity of obesity in children. Severe obesity is a real chronic condition for the difficulties of long-term clinical treatment, the high drop-out rate, the large burden of health and psychological problems and the high probability of persistence in adulthood. A staged approach for weight management is recommended. The establishment of permanent healthy lifestyle habits aimed at healthy eating, increasing physical activity and reducing sedentary behavior is the first outcome, because of the long-term health benefits of these behaviors. Improvement in medical conditions is also an important sign of long-term health benefits. Rapid weight loss is not pursued, for the implications on growth ad pubertal development and the risk of inducing eating disorders. Children and adolescents with severe obesity should be referred to a pediatric weight management center that has access to a multidisciplinary team with expertise in childhood obesity. This article provides pediatricians a comprehensive and evidence based update on treatment recommendations of severe obesity in children and adolescents.

Insulin resistance and impaired glucose tolerance in obese children and adolescents from Southern Italy.

BACKGROUND AND AIM: Obesity in children may lead to insulin resistance and impaired glucose regulation over time. The aim of this study was to investigate the insulin resistance status and the frequency of impaired glucose regulation in obese children and adolescents from the Campania region (Southern Italy), where the prevalence of obesity is among the highest in Europe. METHODS AND RESULTS: We studied 100 (62 male) Italian obese children and adolescents (mean age 10.1+/-2.7 years) and 50 (27 male) normal weight healthy subjects (mean age 10.2+/-2.7 years). Anthropometric measures and biochemical tests were performed in all subjects. In obese patients an oral glucose tolerance test was also performed. The estimate of insulin resistance was calculated by a homeostasis model assessment (HOMA) index. A cut-off HOMA level of >2.5 in children and >4.0 in adolescents was used to identify an insulin-resistance status. Insulin resistance was found in 40.8% of obese children and 41.2% of obese adolescents, whereas it was found in 3.0% of normal children and none of the 17 normal adolescents (p<0.0001 and p<0.002, respectively). None of the subjects had impaired fasting glucose or diabetes, while 4 obese patients had impaired glucose tolerance (4%). CONCLUSIONS: Impaired glucose tolerance is still rare whereas insulin-resistance is already detectable in more than 40% of obese children and adolescents in Southern Italy. Our observations confirm that metabolic risk factors can be found at a very early age and strengthen the case for implementing programmes for prevention and treatment of childhood obesity.

Unexplained bilateral occipital calcification and reduced vision.

An eight year-old girl, investigated because of convulsions, was found to have isolated bilateral presumably cortical and subcortical calcification, reduced visual acuity and prolonged visual evoked response latencies. There were no clinical manifestations of a phakomatosis.