High 1-h glucose in youths with obesity as marker of prediabetes and cardiovascular risk.

PURPOSE: Testing 1-h glucose (1HG) concentration during oral glucose tolerance test is cost-effective to identify individuals at risk of incident type 2 diabetes. Aim of the study was to define 1HG cutoffs diagnostic of incident impaired glucose tolerance (IGT) in youths with obesity, and to evaluate prevalence and association of cutoffs identified in the cohort and from the literature (133 and 155 mg/dl) to cardiovascular disease (CVD) in a population of youths with obesity. METHODS: This is a longitudinal study of 154 youths to identify 1HG cutoffs, and cross-sectional study of 2295 youths to estimate prevalence of high 1HG and association to CVD. Receiver-operating characteristic curves (ROC) were used to establish 1HG cutoffs, and univariate regression analyses to test association of 1HG to blood pressure, lipids and aminotransferases. RESULTS: ROC analysis identified the 1HG cutoff of 159 mg/dl as having diagnostic accuracy of IGT with area under the ROC 0.82 (95% CI 0.66-0.98), sensitivity 0.86% and specificity 0.79%. In the cross-sectional population, prevalence of high 1HG was 36% and 15% for 133 and 155 mg/dl cutoffs, respectively, and 17% for the 159 mg/dl value. All the examined cutoffs were significantly associated with worse lipid profile, liver function test, reduced insulin sensitivity, secretion and disposition index. CONCLUSION: High 1HG is marker of persistent IGT and increased risk of metabolic abnormalities in youths. The 155 mg/dl cutoff is a convenient estimate in young people but longitudinal studies with retinopathy and overt diabetes as end points are advised to verify the 1HG cutoff with the best diagnostic accuracy.

Wrist circumference is a biomarker of adipose tissue dysfunction and cardiovascular risk in children with obesity.

PURPOSE: To evaluate the relationship between wrist circumference, markers of adipose dysfunction, and cardiovascular risk in youths with obesity. METHODS: In this cross-sectional study, we measured body mass composition by dual-energy X-ray absorptiometry, wrist circumference, waist-to-height ratio, fasting blood insulin, glucose, lipid profile, adiponectin, and leptin in 280 children with overweight/obesity and without diabetes (age: 7-18 years). Cardiovascular risk was estimated by "metabolic syndrome score" (MetS score). RESULTS: Study participants had median [25th-75th percentile] wrist circumference of 17.5 [16.7-18.5] cm and waist-to-height ratio of 0.62 [0.59-0.67]. Lower adiponectin-leptin ratio was found among subjects in the upper 50th percentiles of wrist circumference [0.17 (0.09-0.36) vs. 0.38 (0.16-0.79); p < 0.001]. Wrist circumference was independently associated with MetS score (r = 0.5 p < 0.001). Among MetS score components, an independent association between wrist circumference HDLc, triglycerides, and systolic blood pressure was found (r = - 0.253 p < 0.001; r =+ 0.204 p < 0.001; r = + 0.403 p = < 0.001, respectively). The coefficient of determination for MetS score was nominally higher when considering wrist circumference as independent variable (Adj-R2 = 0.30) then when considering body mass index SD (Adj-R2 = 0.28), waist-to-height ratio (Adj-R2 = 0.26) or truncal fat percentage (Adj-R2 = 0.01). The addition of wrist circumference in age and gender adjusted models, accounting to any other anthropometric parameters, resulted in a significant improvement of the Adj-R2 (p < 0.001 for all). CONCLUSIONS: Our study shows that wrist circumference independently relates to adiponectin-leptin ratio and to the prediction of cardiovascular risk, suggesting it as an efficient and adjunctive anthropometric marker of cardiometabolic risk in children with obesity.

25OH vitamin D levels in pediatric patients affected by Prader-Willi syndrome.

PURPOSE: Obesity, insulin resistance, and puberty seem to influence and been inversely associated with 25-hydroxy vitamin D (25OHD) levels. To our knowledge, a study on 25OHD in children and adolescents with Prader-Willi syndrome (PWS), a genetic form of obesity, is not yet available. OBJECTIVE: To analyze the 25OHD values in pediatric PWS subjects in comparison with a control group (CNT), highlighting the possible correlations with IR, BMD, body composition, pubertal stage, and GH therapy (GHT). METHODS: Auxological and laboratory parameters, HOMA-IR, Vitamin D status, and bone density and body composition by DEXA scan were analyzed in 52 PWS and 110 controls (CNT), gender-, age-, and BMI-SD matched. None of them was on calcium or vitamin D. 20 PWS were on growth hormone (GH) therapy and 32 were previously treated. RESULTS AND CONCLUSION: Altogether, PWS had similar values of 25OHD compared to CNT.16 PWS (30.7%) and 27 CNT (24.5%) had low 25OHD levels (< 20 ng/ml) (p = NS). 25OHD of PWS on GHT were comparable to those previously treated. In both groups, univariate analysis showed a negative correlation between 25OHD and fat mass% (FM%). GH therapy and pubertal stage were positively correlated with bone parameters analyzed by DXA. Multivariate regression confirmed only FM% as negative predictor of 25HOD in PWS patients, as previously described. GHT does not seem to influence 25OHD in PWS. CONCLUSION: Our data showed that PWS had similar values of 25OHD compared to CNT. As already described, FM seems to be the only parameter influencing 25OHD levels. Finally, GHT does not seem to influence 25OHD metabolism in PWS.

Early retesting by GHRH + arginine test shows normal GH response in most children with idiopathic GH deficiency.

PURPOSE: Most children with idiopathic isolated GH deficiency (IGHD) normalize GH response to stimulation tests when retested at the completion of growth. The objective of this study was to test the effectiveness of early retesting in challenging the diagnosis of idiopathic IGHD and critically review the diagnostic workup leading to this diagnosis in children with short stature. METHODS: We cross-sectionally retested 38 children with idiopathic IGHD and still on GH treatment. The initial diagnosis of idiopathic IGHD was based on subnormal GH responses to two stimulation tests and normal brain imaging or minor/nonspecific findings at magnetic resonance. The GH response normalization at retesting was considered as the main outcome measure. Clinical features of children who were falsely classified as idiopathic IGHD based on first GH testing were retrospectively analyzed. RESULTS: GH secretion was normal in 36/38 children (95%). Two children showed slightly reduced peak GH responses and normal IGF-I levels. Fourteen children underwent GH retesting before puberty, 24 children during puberty. CONCLUSION: The diagnostic process should be improved to minimize the rate of false positive at GH testing and, in case of unsatisfactory response to GH treatment, the diagnosis of isolated idiopathic GHD should be challenged with early retesting.

Serum insulin-like growth factor-I (IGF-I) reference ranges for chemiluminescence assay in childhood and adolescence. Data from a population of in- and out-patients.

BACKGROUND: Insulin-like growth factor I (IGF-I) measurement is widely used for the diagnosis of disorders of GH secretion and sensitivity, and for monitoring of both GH and IGF-I replacement therapies. However, the lack of appropriate reference values obtained from large and representative samples undermines its practical utility. OBJECTIVE: To establish IGF-I reference values for a commonly used enzyme-labeled chemiluminescent immunometric assay in a large population of children aged 0 to 18 years. DESIGN: Cross-sectional analysis of serum IGF-I levels from samples collected in the two major Italian Children's Hospitals. SUBJECTS AND METHODS: IGF-I was measured using a solid-phase, enzyme-labeled chemiluminescent immunometric assay in 24403 children (50.6% girls) aged 0 to 18 years. Quantile regression coupled to multivariable fractional polynomials was used to produce age- and sex-specific reference values. MAIN OUTCOME MEASURE: Age- and sex-specific IGF-I reference values. RESULTS AND CONCLUSION: Reference values for immunometric assay of IGF-I were produced in a large sample of children and adolescents. Prediction equations were provided to automatize their calculations.

Responses to GHRH plus arginine test are more concordant with IGF-I circulating levels than responses to arginine and clonidine provocative tests.

BACKGROUND/OBJECTIVE: Although pharmacological GH stimulation tests are still considered the gold standard for GH deficiency (GHD) diagnosis, they are burdened by poor specificity. The majority of children diagnosed as having GHD show normal GH responses when re-tested at the end of growth, thus questioning the initial diagnosis. We evaluated the concordance between IGF-I levels and GH responses to provocative tests. METHODS: We analyzed 105 GHRH plus arginine tests, 79 arginine tests, and 124 clonidine tests performed in 192 short children. IGF-I levels ≤-2SD score (SDS) were considered suggestive for high likelihood of GHD. The percentage of positive and negative results for each test was determined and compared with IGF-I levels, clinical follow-up and response to therapy. RESULTS: In children with IGF-I>-2SDS the arginine test showed a concordance rate of 6.9%, the clonidine test of 28.6%, and GHRH plus arginine test of 70%. In children with IGF-I≤-2SDS the concordance was 96.1%, 85.7%, and 46.4%, respectively. The overall concordance was 66.7% for GHRH plus arginine, 42.7% for clonidine, and 27.8% for arginine tests. CONCLUSION: Our results suggest that GHRH plus arginine test provides the best concordance with the assessment of IGF-I levels thus suggesting that the combination of the two procedures may significantly reduce the need of a second provocative test.