New liquid chromatography tandem mass spectrometry reference data for estradiol show mini-puberty in both sexes and typical pre-pubertal and pubertal patterns.

CONTEXT: Reliable estradiol (E2) reference intervals (RIs) are crucial in pediatric endocrinology. OBJECTIVES: This study aims to develop a sensitive ultra-performance liquid chromatographic tandem mass spectrometry (UPLC-MS/MS) method for E2 in serum, to establish graphically represented RI percentiles and annual RIs for both sexes, and to perform a systematic literature comparison. METHODS: First, a UPLC-MS/MS method for E2 was developed. Second, graphically represented RI percentiles and annual RIs covering 0-18 years were computed (cohort of healthy children [1181 girls and 543 boys]). Subsequently, RIs were compared with published data by systematic searches. RESULTS: Lower limit of quantification was 11 pmol/L, indicating high sensitivity. Estradiol first peaked during mini-puberty in both sexes (girls up to 192 pmol/L; boys up to 225 pmol/L). As could be expected, girls showed higher pubertal E2 (up to 638 pmol/L). However, boys' RIs (up to 259 pmol/L) overlapped considerably. We found 4 studies in the literature that also used LC-MS/MS to determine E2 and published RIs for the complete pediatric age range. Reference intervals varied considerably. Pre-pubertal and pubertal phases were present in all studies. Higher E2 during the time of mini-puberty in both sexes was documented in 3 studies including ours. CONCLUSIONS: Variability of RIs for E2 between studies illustrates the importance of laboratory-specific RIs despite using a LC-MS/MS reference method. In boys, the striking E2 peak during mini-puberty as well as high pubertal E2 without phenotypic estrogenization in regular male puberty indicates that the role of E2 in children and, especially in boys, requires better functional understanding.

Cardiorespiratory fitness in adolescents and young adults with Klinefelter syndrome - a pilot study.

Background: Klinefelter syndrome (KS) may be associated with a wide spectrum of phenotypic changes including endocrine, metabolic, cognitive, psychiatric and cardiorespiratory pathologies in adults. However, in adolescence the clinical phenotype of KS is not well described, especially regarding physical fitness. The present study reports on cardiorespiratory function in adolescents and young adults with KS. Methods: Adolescents and young adults with KS were recruited in a cross-sectional pilot study. Biochemical parameters of fitness including hormonal status, a body impedance analysis, the grip strength, the amount of physical activity at home for 5 days via trackbands and anamnestic parameters were assessed. In addition, participants underwent an incremental symptom-limited cardiopulmonary exercise test (CPET) on a bicycle ergometer. Results: Nineteen participants with KS aged 15.90 ± 4.12 years (range: 9.00 - 25.00) participated in the study. Pubertal status was Tanner 1 (n = 2), Tanner 2 - 4 (n = 7) and Tanner 5 (n = 10). Seven participants received testosterone replacement therapy. Mean BMI z-score was 0.45 ± 1.36 and mean fat mass was 22.93% ± 9.09. Grip strength was age-appropriate or above normal. 18 participants underwent CPET with subnormal results for maximum heart rate (z-score -2.84 ± 2.04); maximum workload (Wattmax; z score -1.28 ± 1.15) and maximum oxygen uptake per minute (z- score -2.25 ± 2.46). Eight participants (42.1%) met the criteria for chronotropic insufficiency (CI). Data from track-bands showed sedentary behavior for 81.15% ± 6.72 of the wear time. Conclusion: A substantial impairment of cardiopulmonary function can be detected in this group of boys to young adults with KS, including chronotropic insufficiency in 40%. The track-band data suggest a predominantly sedentary lifestyle, despite normal muscular strength as assessed via grip strength. Future studies need to investigate the cardiorespiratory system and its adaption to physical stress in a larger cohort and in more detail. It is feasible that the observed impairments contribute to the avoidance of sports in individuals with KS and may contribute to the development of obesity and the unfavorable metabolic phenotype.

Childhood obesity is associated with changes in the serum metabolite profile.

OBJECTIVE: The human serum metabolite profile is reflective of metabolic processes, including pathophysiological changes characteristic of diseases. Therefore, investigation of serum metabolite concentrations in obese children might give new insights into biological mechanisms associated with childhood obesity. METHODS: Serum samples of 80 obese and 40 normal-weight children between 6 and 15 years of age were analyzed using a mass spectrometry-based metabolomics approach targeting 163 metabolites. Metabolite concentrations and metabolite ratios were compared between obese and normal-weight children as well as between children of different pubertal stages. RESULTS: Metabolite concentration profiles of obese children could be distinguished from those of normal-weight children. After correction for multiple testing, we observed 14 metabolites (glutamine, methionine, proline, nine phospholipids, and two acylcarnitines, p < 3.8 × 10⁻4) and 69 metabolite ratios (p < 6.0 × 10⁻6) to be significantly altered in obese children. The identified metabolite markers are indicative of oxidative stress and of changes in sphingomyelin metabolism, in ß-oxidation, and in pathways associated with energy expenditure. In contrast, pubertal stage was not associated with metabolite concentration differences. CONCLUSION: Our study shows that childhood obesity influences the composition of the serum metabolome. If replicated in larger studies, the altered metabolites might be considered as potential biomarkers in the generation of new hypotheses on the biological mechanisms behind obesity.

SDCCAG8 obesity alleles and reduced weight loss after a lifestyle intervention in overweight children and adolescents.

Genome-wide association analyses (GWAS) contributed to the detection of a number of single-nucleotide polymorphisms (SNPs) associated with obesity. However, little is known about the impact of the obesity-risk alleles on weight loss-related phenotypes after lifestyle interventions. A recent meta-analysis of GWAS reported five genomic loci near or in the genes FTO, MC4R, TMEM18, SDCCAG8, TNKS/MSRA that were associated with obesity in children and adolescents. Here, we analyzed the effect of the 10 SNPs representative of the five loci on measures of weight loss and cardiometabolic risk after a 1-year lifestyle intervention in 401 children and adolescents (mean age 10.74 years; 55.4% female; mean BMI 27.42 kg/m(2), mean BMI-standard deviation score (SDS) 2.37). For confirmation of one locus genotyping of three intronic SNPs in SDCCAG8 was performed in 626 obese adults who completed the 10-week hypoenergetic diet program. Intronic variants of SDCCAG8, which are associated with early onset obesity, are associated with reduced weight loss after a 1-year lifestyle intervention in overweight children and adolescents even after adjusting for age, sex, baseline measurement, or multiple testing (all P < 10(-6)). However, our results could not be confirmed in 626 obese adults undertaking a hypoenergetic diet intervention.

Effect of lifestyle intervention on features of polycystic ovarian syndrome, metabolic syndrome, and intima-media thickness in obese adolescent girls.

CONTEXT: Polycystic ovarian syndrome (PCOS) is associated with cardiovascular risk factors (CRF). Lifestyle intervention is regarded as therapy of choice even if studies in adolescent girls with PCOS are scarce. OBJECTIVE: Our objective was to analyze the impact of lifestyle intervention on menses irregularities, hyperandrogenemia, CRF, and intima-media thickness (IMT) in adolescent girls with PCOS. PATIENTS: Patients included 59 obese girls with PCOS aged 12-18 yr. INTERVENTION: Intervention was a 1-yr lifestyle intervention based on nutrition education, exercise training, and behavior therapy. MAIN OUTCOME MEASURES: Menses cycles, IMT, waist circumference, blood pressure, fasting lipids, insulin, glucose, testosterone, dehydroepiandrosterone sulfate, androstenedione, and SHBG were evaluated. RESULTS: In contrast to the 33 girls without weight loss, the 26 girls reducing their body mass index during the lifestyle intervention (by a mean of -3.9 kg/m(2)) improved most CRF and decreased their IMT (by a mean of -0.01 cm). Testosterone concentrations decreased (by a mean of -0.3 nmol/liter) and SHBG concentrations increased (by a mean of +8 ng/ml) significantly in girls with weight loss in contrast to girls with increasing weight. The prevalence of amenorrhea (-42%) and oligoamenorrhea (-19%) decreased in the girls with weight loss. The changes in insulin in the 1-yr follow-up were significantly correlated to changes in testosterone (r = 0.38; P = 0.002) and SHBG (r = -0.35; P = 0.048). A linear regression model with changes in IMT as dependent variable demonstrated a significant association with changes in blood pressure and weight status but not with changes in testosterone. CONCLUSIONS: Weight loss due to lifestyle intervention is effective to treat menses irregularities, normalize androgens, and improve CRF and IMT in obese adolescent girls with PCOS.

Obesity in children and adolescents: relationship to growth, pubarche, menarche, and voice break.

OBJECTIVE: The relationships between obesity, pubertal development, and height are controversial. Therefore, we compared the prevalence of pubarche, menarche, and voice break between a large collective of obese and normal-weight children and adolescents aged 10-16 years. METHODS: We assessed weight, height, pubarche, menarche, and voice break in 1383 obese German children and in 6615 children of a representative national German cohort aged 10-16 years. In all obese children, gonadotropins were determined and birth weight data were collected. RESULTS: Independently of gender, the height standard deviation score (SDS) was significantly greater (0.3-1.0) in obese children <14 years compared to the reference cohort. Independently of age, the percentage of obese boys with pubarche was significantly lower compared to age-matched normal-weight boys. In girls <13 years, the prevalence of obese girls with pubarche was significantly lower compared to age-matched normal-weight girls. In boys > or =11 years, the percentage of obese boys with change of voice was significantly lower compared to age-matched normal-weight boys. In girls > or =11 years, the prevalence of obese girls with menarche was significantly lower compared to age-matched normal-weight girls. Birth weight had no impact on pubarche in the obese children. Luteinizing hormone was > 0.3 IU/L in 86% of the children > or =10 years with pubarche. CONCLUSIONS: Obese children are taller than normal-weight children up to the age of 14 years. Since obese children demonstrated pubarche, menarche, and voice break later than their normal-weight peers, the increase in height in obese children does not seem to be attributable to earlier onset of puberty.

Relationship between MTNR1B (melatonin receptor 1B gene) polymorphism rs10830963 and glucose levels in overweight children and adolescents.

AIMS: The G-allele of the single nucleotide polymorphism (SNP) rs10830963 in MTNR1B (melatonin receptor 1B gene) is associated with type 2 diabetes mellitus and glucose levels in adults. The aim of this study was to analyze whether there is an allele-dosage effect on glucose metabolism in overweight children and to explore if changes in glucose metabolism in a lifestyle intervention do also depend on genotype. METHODS: We genotyped rs10830963 in 1118 overweight children and adolescents [mean age 10.7 yr, mean body mass index (BMI) 27.8 kg/m2]; 340 of these individuals completed a 1-yr lifestyle intervention (mean age 10.7 yr, mean BMI 27.9 kg/m2). The degree of overweight [BMI-SDS (standard deviation score)], fasting insulin, glucose, homeostasis model assessment for insulin resistance (HOMA-IR), and quantitative insulin sensitivity check index (QUICKI) were measured before and after intervention. RESULTS: We showed a significant relationship between rs10830963 and basal glucose levels [ß:1.101, 95% confidence interval (CI) 0.316-1.886 mg/dL per risk allele; p = 0.006] by linear regression adjusted for age, age(2), and sex. There was no effect of the allele on insulin or indices of insulin resistance or sensitivity. After the 1-yr lifestyle intervention, we observed a significant reduction of BMI-SDS as well as an improvement of HOMA-IR and QUICKI, but no evidence for an association between rs10830963 genotype and changes of glucose levels. CONCLUSIONS: The G-allele of rs10830693 in the MTNR1B gene was significantly related to glucose levels, while an impact of this genetic variant on the changes in glucose metabolism in children participating in a lifestyle intervention was not observable.

Longitudinal association between IGFBP-1 levels and parameters of the metabolic syndrome in obese children before and after weight loss.

BACKGROUND: Insulin-like growth factor binding protein 1 (IGFBP-1) is a marker of insulin resistance. We hypothesized that IGFBP-1 is associated with the metabolic syndrome (MetS), which is related to insulin resistance. METHODS: We examined 51 obese Caucasian children (mean age 12.1 ? 2.3, 55% male, mean body mass index [BMI] 31.8 ? 4.8 kg/m(2)). Anthropometrical markers, pubertal stage, hepatic ultrasound, waist circumference, blood pressure, fasting serum IGFBP-1, IGFBP-3, IGF-I, adiponectin, leptin, transaminases, glucose, insulin, triglycerides, and HDL-cholesterol concentrations were determined at onset and the end of the one-year lifestyle intervention. RESULTS: In contrast to IGF-I and IGFBP-3, IGFBP-1 correlated significantly to most parameters of the MetS in cross-sectional (waist circumference: r = -0.45, triglycerides: r = -0.29; insulin: r = -0.31; HOMA: r = -0.30) and longitudinal analyses (? triglycerides: r = ?0.22; ? Insulin: r = ?0.25; ? HOMA: r = ?0.62). The association between changes of HOMA and changes of IGFBP-1 was stronger than the associations between changes of leptin or adiponectin, and changes of HOMA. The risk for the MetS was inversely related to IGFBP-1 levels (odds ratio:-0.05 per additional IGFBP-1 unit; 95% confidence interval: -0.08 up to -0.02; p = 0.019) in a multiple logistic regression analyses adjusted to BMI, pubertal stage, age, and gender. The nine obese children with the MetS had significantly lower IGFBP-1 levels (1.6 ? 1.3 ngm/l) than the 42 obese children without the MetS (4.0 ? 3.8 ng/ml). The eleven obese children with fatty liver assessed by ultrasound had significantly lower IGFBP-1 levels (1.5 ? 1.3 ngm/l) than the 40 obese children without fatty liver (4.2 ? 4.1 ng/ml). CONCLUSION: The strong relationships between IGFBP-1, insulin resistance, and the MetS suggest that IGFBP-1 might be a promising marker for these entities in obesity. This study is registered at clinicaltrials.gov (NCT00435734).

Body mass index patterns over 5 y in obese children motivated to participate in a 1-y lifestyle intervention: age as a predictor of long-term success.

BACKGROUND: Long-term outcome after lifestyle interventions in obese children is largely unknown but important to improving intervention. OBJECTIVE: The aim was to identify predictors of long-term changes in body mass index (BMI) after lifestyle intervention. DESIGN: Annual changes in the BMI SD score (BMI-SDS) over 5 y in 663 obese children (aged 4-16 y) motivated to participate in an outpatient lifestyle intervention were analyzed. Child-specific longitudinal curves based on multilevel growth curve models (MLMs) over 5 y were estimated depending on patient characteristics (age and sex). RESULTS: The mean decrease in BMI-SDS was 0.36 (95% CI: 0.33, 0.39) at the end of the 1-y intervention and 0.46 (95% CI: 0.36, 0.55) 4 y after the intervention. Change in BMI-SDS in the intervention period predicted long-term outcome after 5 y (P < 0.001). MLMs identified age but not sex as a predictor of the outcome: the youngest children (<8 y) at the onset of the intervention had the greatest decrease in BMI-SDS over 5 y, and the oldest children (>13 y) had the least decrease in BMI-SDS (P < 0.05). Whereas there was a larger reduction in BMI-SDS during the intervention in children aged 8-10 y than in children aged 11-12 y, long-term decrease in BMI-SDS was greater in 11-12-y-old children (P < 0.001). CONCLUSIONS: Younger age was associated with the best long-term outcome after participation in the lifestyle intervention, which supports the need for early intervention in childhood obesity. Children aged 8-10 y may need modified intervention, because BMI-SDS increased more in the older children in the long term. However, mean BMI-SDS was significantly lower 4 y after the end of the intervention than at baseline in all age groups. This study was registered at clinicaltrials.gov as NCT00435734.

Former small for gestational age (SGA) status is associated to changes of insulin resistance in obese children during weight loss.

OBJECTIVE: Former small for gestational age (SGA) children are at risk of both obesity and insulin resistance. Longitudinal studies are required to assess a possible relationship between former SGA status and insulin resistance independent of weight status. We hypothesized that obese children with former appropriate for gestational age (AGA) status improve their insulin resistance during weight loss more effectively compared to obese children with former SGA status. METHODS: A 1-yr longitudinal follow-up study design was adopted in the primary care setting and 341 obese children [8% SGA, mean age 10.5 +/- 0.1 yr, body mass index (BMI) 27.7 +/- 0.2, BMI-standard deviation score (SDS) 2.47 +/- 0.02] were taken for the study. Outpatient 1-yr intervention was based on exercise, behavior and nutrition therapy. We measured insulin resistance index following the Homeostasis model assessment model (HOMA), blood pressure, lipids, glucose, and insulin in all children before and after the 1-yr intervention. RESULTS: In a multiple linear regression analysis adjusted for age, gender, and pubertal stage, changes of HOMA were significantly related to changes of BMI-SDS (-2.55 per loss of 1 BMI-SDS unit; p < 0.001) and SGA status (+2.05 for SGA children; p < 0.001). Changes of BMI-SDS together with gender and age explained 10% of the variance of changes of HOMA, while SGA status explained an additional 4%. After adjustment for age, sex, pubertal stage, and BMI-SDS, former SGA status was not significantly related to any other considered cardiovascular risk factor. CONCLUSIONS: Change of weight status predicted change of HOMA in obese children participating in a lifestyle intervention. Changes of HOMA were also predicted by former SGA status supporting that former SGA status influences insulin resistance.

Association between androgens, intima-media thickness and the metabolic syndrome in obese adolescent girls.

BACKGROUND: While an association between androgens and the metabolic syndrome (MS) is well established in obese women, studies concerning this relationship are scarce in obese adolescent girls. Therefore, we analysed the relationships between androgens, MS and intima-media thickness (IMT) in this age-group. METHODS: In 160 obese girls (aged 12-18 years, mean BMI: 32.6 +/- 5.0 kg/m((2))), androgens [testosterone, dehydroepiandrosterone sulphate (DHEA-S), androstenedione], SHBG and the components of MS (waist circumference, blood pressure (BP), lipids, uric acid, insulin, glucose, 2 h glucose in oral glucose tolerance test (oGTT)) were studied. Furthermore, IMT was determined in a subgroup of 71 randomly chosen girls. RESULTS: Testosterone correlated significantly to systolic BP (r = 0.20), diastolic BP (r = 0.24), 2 h glucose in oGTT (r = 0.30), triglycerides (r = 0.19), uric acid (r = 0.17), waist circumference (r = 0.25) and IMT (r = 0.54). These relationships (except for waist circumference and uric acid) were independent of BMI and insulin resistance index homeostasis model assessment. In contrast to testosterone, DHEA-S, androstenedione and SHBG showed no or weaker correlations to any parameter of MS. The 48 girls with MS demonstrated significantly higher testosterone (1.8 +/- 0.7 nmol/l; P = 0.025) and DHEA-S (4.7 +/- 2.3 micromol/l; P = 0.008) concentrations as compared with the 112 girls without MS (mean testosterone 1.5 +/- 0.7 nmol/l, mean DHEA-S 3.6 +/- 2.3 micromol/l). CONCLUSIONS: Testosterone was significantly related to MS and its components in obese adolescent girls independently of BMI and insulin resistance. As IMT was significantly associated with testosterone, this supports the clinical relevance of this finding.

Risk factors for impaired glucose tolerance in obese children and adolescents.

AIM: To investigate which obese children have an increased risk for impaired glucose tolerance (IGT), a risk factor for later diabetes. METHODS: We studied 169 European untreated obese children and adolescents with normal glucose tolerance at baseline. Waist circumference, fasting glucose, lipids, blood pressure, pubertal stage, 2 h glucose in oral glucose tolerance test (oGTT), and HbA1c were determined at baseline and 1 year later. RESULTS: One year after baseline, 19 (11.2%) children demonstrated IGT, 4 (2.4%) children had impaired fasting glucose, no (0%) child suffered from diabetes, and 146 (86%) children still showed normal glucose tolerance. At baseline, the children with IGT and with normal glucose tolerance in a one-year follow-up did not differ significantly in respect of any analyzed parameter, apart from pubertal stage. The children developing IGT entered puberty significantly more frequently (37% vs 3%, P < 0.001). One year after baseline, the children with IGT demonstrated significantly increased waist circumference, blood pressure values, insulin and triglyceride concentrations, and insulin resistance index HOMA. The children remaining in the normal glucose tolerance status 1 year after baseline did not demonstrate any significant changes. CONCLUSION: During the study period of 1 year, more than 10% of the obese children with normal glucose tolerance converted to IGT. Repeated screening with oGTT seems meaningful in obese children entering puberty or demonstrating increased insulin resistance, waist circumference, blood pressure, or triglyceride concentrations.

Leptin concentrations are a predictor of overweight reduction in a lifestyle intervention.

OBJECTIVE: Leptin resistance is discussed to be involved in the genesis of obesity. Therefore, we hypothesized that leptin levels were negatively associated with degree of weight loss in obese children participating in a lifestyle intervention. METHODS: We studied 248 obese children aged 8-14 years attending the "Obeldicks" lifestyle intervention (mean age 10.6+/-0.2 years, 53% female, 48% pubertal, mean body mass index (BMI) 27.8+/-0.3 kg/m2, and mean standard deviation score [SDS]-BMI 2.43+/-0.03). Baseline leptin concentrations were correlated with change of weight status, waist circumference, and percentage body fat, as calculated from skinfold measurements in the one-year intervention by Pearson correlation and multiple linear regression analyses. Furthermore, the relationship between leptin and cardiovascular risk factors (insulin, insulin resistance index HOMA, blood pressure, lipids, and glucose) were analyzed. RESULTS: A total of 212 children (85%) reduced their overweight, 9 children (4%) dropped out, and 27 children (11%) did not reduce their overweight in the lifestyle intervention "Obeldicks". The mean reduction of SDS-BMI was 0.34+/-0.02. The reduction of SDS-BMI (r=- 0.27), waist circumference (r=- 0.64), and percentage body fat (r=- 0.26) were significantly negatively associated with baseline leptin levels both in univariate analyses and in multiple regression analyses, adjusted to baseline age, BMI, gender and pubertal stage. Baseline leptin concentrations were significantly associated with BMI, pubertal stage, gender, waist circumference, and insulin, but not to any other cardiovascular risk factors in multiple regression analyses. CONCLUSIONS: The finding that baseline leptin concentrations were significantly negatively correlated with the degree of weight loss in a lifestyle intervention supports the hypothesis of leptin resistance in obesity. This study is registered at clinicaltrials.gov (NCT00435734).

Lifestyle intervention in obese children is associated with a decrease of the metabolic syndrome prevalence.

BACKGROUND: Weight loss is the appropriate approach to reduce the obesity-related health risk. However, the effect of lifestyle interventions on the metabolic syndrome prevalence has been rarely studied in obese children. METHODS: We analyzed changes of weight status, 2h glucose levels from oral glucose tolerance tests (oGTT), fasting glucose, lipids, blood pressure, and the prevalence of metabolic syndrome in relation to a 1-year outpatient lifestyle intervention in 288 obese children (45% male; mean age 12.5 years, mean SDS-BMI 2.48). These data were compared to 186 obese children without intervention with similar distributions of age, gender, and weight status. RESULTS: Lifestyle intervention led to a significant decrease of SDS-BMI (mean -0.22; 95%CI -0.18 to -0.26), while SDS-BMI increased significantly in children without intervention (mean +0.15; 95%CI +0.13 to +0.18). Children with lifestyle intervention had a significant decrease of metabolic syndrome prevalence (from 19% to 9%; definition according to IDF) and an improvement of waist circumference, blood pressure, and 2h glucose values in the oGTT in contrast to obese children without intervention. The degree of weight loss was significantly associated with the amount of improvement of the components of the metabolic syndrome. Particularly, the children with a SDS-BMI reduction >0.5 showed an improvement of all components of the metabolic syndrome. CONCLUSIONS: Lifestyle intervention led to weight loss and an improvement of the metabolic syndrome and its components. Degree of weight loss was associated with the improvement of the prevalence of metabolic syndrome and its components.

Small for gestational age status is associated with metabolic syndrome in overweight children.

OBJECTIVE: Small for gestational age (SGA) children are at risk of both later obesity and metabolic syndrome (MetS). However, it is unknown whether obesity or SGA status leads to MetS in these subjects. We hypothesized that overweight children with former SGA status had more present components of the MetS than overweight children with former appropriate for gestational age (AGA) status. METHODS: We analyzed 803 overweight children (4% SGA, mean age 11+/-0.1 years, body mass index (BMI) 27.3+/-0.2, SDS-BMI 2.32+/-0.02) concerning blood pressure, lipids, glucose, and insulin. Oral glucose tolerance tests (oGTT) were performed in all 35 former SGA children and 147 randomly chosen former non-SGA children. RESULTS: After adjustment for age, sex, pubertal stage, and BMI-SDS, former SGA status was significantly related to blood pressure, triglyceride, insulin, and 2 h glucose levels in oGTT. The MetS prevalence was more than doubled in overweight former SGA subjects (40% MetS) compared with overweight former AGA subjects (17% MetS). The corresponding adjusted odds ratio was 4.08 (95% confidence interval 1.48 to 11.22) for SGA compared with AGA children. CONCLUSIONS: Overweight former SGA children had an increased risk for the components of the MetS compared with overweight former AGA children. Therefore, SGA status seems to be a risk factor for the MetS independently of weight status. Particularly overweight children with former SGA status should be screened for the MetS.

Parental diabetes, pubertal stage, and extreme obesity are the main risk factors for prediabetes in children and adolescents: a simple risk score to identify children at risk for prediabetes.

OBJECTIVES: The current worldwide increase of prediabetes defined as impaired fasting glucose or impaired glucose tolerance and type 2 diabetes mellitus (T2DM) coincides the increase of obesity. However, it is unclear that which children have an increased risk and should be screened for prediabetes. METHODS: We studied 437 overweight children and adolescents to identify risk factors for prediabetes. A risk score for prediabetes was calculated using logistic regression. This score was examined in a second, independent cohort of 567 overweight children and adolescents. History of T2DM in parents and grandparents, degree of overweight, age, pubertal stage, birth weight, hypertension, dyslipidemia, acanthosis nigricans, and abdominal obesity were considered as potential risk factors. RESULTS: The frequency of prediabetes was 6% in sample 1 and 17% in sample 2. The strongest association was observed for history of parental diabetes with an adjusted odds ratio (aOR) of 9.5 [95% confidence interval (CI) 2.5-36.4] in sample 1 and 6.3 (95% CI 3.7-10.7) in sample 2, followed by pubertal stage with an aOR of 5.5 (95% CI 0.7-45.4) in sample 1 and 6.2 (95% CI 2.4-15.6) in sample 2, and by extreme obesity with an aOR of 5.0 (95% CI 1.7-15.3) in sample 1 and 3.3 (95% CI 2.0-5.4) in sample 2. CONCLUSIONS: The main risk factors for prediabetes were parental diabetes, pubertal stage, and extreme obesity. Screening for prediabetes seems meaningful in subjects with either a parental history of diabetes or a combination of extreme obesity and pubertal stage and detected nearly 90% of the overweight children and adolescents with prediabetes.