N-terminally truncated (96-585) GAD65 (tGAD65) auto antibodies may better delineate type 1 diabetes than full-length GAD65 (fGAD65) autoantibodies. We aimed to compare the diagnostic sensitivity and specificity between fGAD65 and tGAD65 autoantibodies for type 1 diabetes in relation to HLA-DQ. Sera from children and adolescents with newly diagnosed type 1 diabetes (n = 654) and healthy control subjects (n = 605) were analyzed in radiobinding assays for fGAD65 (fGADA), tGAD65 (tGADA), and commercial 1251-GAD65 (RSRGADA) autoantibodies. The diagnostic sensitivity and specificity in the receiver operating characteristic curve did not differ between fGADA and tGADA. At the optimal cutoff, the diagnostic sensitivity for fGADA was lower than tGADA at similar diagnostic specificities. In 619 patients, 64% were positive for RSRGADA compared with 68% for fGADA and 74% for tGADA. Using non-DQ2/non-DQ8 patients as reference, the risk of being diagnosed with fGADA and tGADA was increased in patients with DQ2/2 and DQ2/8. Notably, logistic regression analysis suggested that DQ8/8 patients had an increased risk to be diagnosed with tGADA (P = 0.003) compared with fGADA (P = 0.09). tGADA had a higher diagnostic sensitivity for type 1 diabetes than both fGADA and RSRGADA. As D08/8 patients represent 10-11% of patients with newly diagnosed type 1 diabetes <18 years of age, tGADA analysis should prove useful for disease classification.

N-terminally truncated (96–585) GAD65 (tGAD65) autoantibodies may better delineate type 1 diabetes than full-length GAD65 (fGAD65) autoantibodies. We aimed to compare the diagnostic sensitivity and specificity between fGAD65 and tGAD65 autoantibodies for type 1 diabetes in relation to HLA-DQ. Sera from children and adolescents with newly diagnosed type 1 diabetes (n = 654) and healthy control subjects (n = 605) were analyzed in radiobinding assays for fGAD65 (fGADA), tGAD65 (tGADA), and commercial 125I-GAD65 (RSRGADA) autoantibodies. The diagnostic sensitivity and specificity in the receiver operating characteristic curve did not differ between fGADA and tGADA. At the optimal cutoff, the diagnostic sensitivity for fGADA was lower than tGADA at similar diagnostic specificities. In 619 patients, 64% were positive for RSRGADA compared with 68% for fGADA and 74% for tGADA. Using non-DQ2/non-DQ8 patients as reference, the risk of being diagnosed with fGADA and tGADA was increased in patients with DQ2/2 and DQ2/8. Notably, logistic regression analysis suggested that DQ8/8 patients had an increased risk to be diagnosed with tGADA (P = 0.003) compared with fGADA (P = 0.09). tGADA had a higher diagnostic sensitivity for type 1 diabetes than both fGADA and RSRGADA. As DQ8/8 patients represent 10–11% of patients with newly diagnosed type 1 diabetes <18 years of age, tGADA analysis should prove useful for disease classification.

Background A number of large studies have shown phenotypic differences between first-borns and later-borns among adult men. In this study, we aimed to assess whether birth order was associated with height and BMI in a large cohort of Swedish women.Methods Information was obtained from antenatal clinic records from the Swedish National Birth Register over 20 years (1991-2009). Maternal anthropometric data early in pregnancy (at approximately 10-12 weeks of gestation) were analysed on 13 406 pairs of sisters who were either first-born or second-born (n=26 812).Results Early in pregnancy, first-born women were of BMI that was 0.57 kg/m(2) (2.4%) greater than their second-born sisters (p<0.0001). In addition, first-borns had greater odds of being overweight (OR 1.29; p<0.0001) or obese (OR 1.40; p<0.0001) than second-borns. First-borns were also negligibly taller (+1.2 mm) than their second-born sisters. Of note, there was a considerable increase in BMI over the 18-year period covered by this study, with an increment of 0.11 kg/m(2) per year (p<0.0001).Conclusions Our study corroborates other large studies on men, and the steady reduction in family size may contribute to the observed increase in adult BMI worldwide.

OBJECTIVES:The study aimed to determine the prevalence of hyperglycemia in sick children admitted into the emergency rooms and to investigate its relationship with adverse outcomes.METHODS:A prospective study involving 2 tertiary hospitals in Lagos. Study subjects included all children aged beyond 1 month. An Accu-Chek Active glucometer was used for the bedside blood glucose determination. Hyperglycemia was defined as blood glucose greater than 7.8 mmol/L.RESULTS:A total of 1045 patients were recruited with hyperglycemia being recorded in 135 patients (prevalence rate of 12.9%). Mean age of the hyperglycemic patients was 29.0 ± 31.23 months. Prevalence rates of hyperglycemia among the leading diagnoses were 17.4% in acute respiratory tract infections, 11% in malaria, 15.3% in septicemia, 14.9% in gastroenteritis, and 18.2% in burns. Other conditions include sickle cell anemia, meningitis, and malnutrition. Mortality rate was significantly higher overall in hyperglycemic compared with the normoglycemic patients (15.4% vs 8.0%, P = 0.011). With regard to specific diagnoses, significantly higher mortality rates were recorded in hyperglycemic patients with acute respiratory tract infections (28% vs 8%, P = 0.011) and malaria (21.4% vs 5.0%, P = 0.006) than in their normoglycemic counterparts.CONCLUSIONS:Hyperglycemia is common in ill children admitted to the emergency rooms and is associated with 2 to 4 times higher mortality in common childhood diseases encountered. Blood glucose determination is important in all acutely ill children at presentation. The practice of empirical administration of intravenous glucose in some resource-constrained facilities where blood glucose testing facilities are not readily available should be discouraged.

Background/Aims: We investigated the association between cognition and growth hormone (GH) status and GH treatment in short prepubertal children with broadly ranging GH secretion. Methods: A total of 99 children (age 3-11 years), 41 with GH deficiency (GHD) and 58 with idiopathic short stature (ISS), were randomized to a fixed dose (43 µg/kg/day) or a prediction model-guided individualized dose (17-100 µg/kg/day) and followed up for 24 months. In a longitudinal and mixed within- and between-subjects study, we examined clinical effect size changes, measured by Cohen's d, in full-scale IQ (FSIQ) and secondary IQ indices. Results: Significant increases giving medium effect size in FSIQ (p = 0.001, Cohen's d = 0.63), performance IQ (p = 0.001, Cohen's d = 0.65) and processing speed (p = 0.005, Cohen's d = 0.71) were found in the GH-deficient group. In contrast, perceptual organization only increased in the ISS group (p = 0.001, Cohen's d = 0.53). Baseline IQ was normally distributed with small but significant differences between the groups: GH-deficient children had lower FSIQ (p = 0.042) and lower performance IQ (p = 0.021). Using multiple regression analysis, 40% of the variance in delta processing speed scores (0-24 months) was explained by GHmax and IGF-ISDS at baseline. Conclusion: IQ, specifically fluid intelligence, increased in the GH-deficient children. The pretreatment status of the GH/IGF-I axis was significantly predictive for these changes.

Clitoral size references are useful for diagnosing genital abnormalities. Despite the fact that examining the genitalia is an important aspect of newborn evaluation, few studies have been carried out to determine normal clitoral size in newborn infants. The aim of this study was to establish reference values for clitoral size in Nigerian newborn girls and to compare them with references from other ethnic populations. A total of 244 healthy newborn girls delivered at 28–43 weeks gestation were enrolled in the study, and clitoral lengths and widths were measured at <72 hours. The mean clitoral length was 7.7 mm with a standard deviation of ±1.37 mm, while the mean clitoral width was 4.40 ± 0.89 mm. The clitoral length was significantly longer than those reported for Caucasian (4.00 ± 1.24 mm), Korean (3.82 ± 1.47), Turkish (4.93 ± 1.61) and Japanese (4.30 ± 1.10) babies. The present results make it possible to evaluate clitoral size in Nigerian newborn baby girls in an objective way, to identify genital abnormalities and endocrine disorders. Based on this study, a clitoral length of more than 10 mm would be considered clitoromegaly in a newborn girl in Nigeria.

Responsiveness to GH treatment can be estimated by both growth and ∆IGF-I. The primary aim of the present study was to investigate if mimicking the physiological increase during puberty in GH secretion, by using a higher GH dose could lead to pubertal IGFs in short children with low GH secretion. The secondary aim was to explore the relationship between IGF-I, IGFBP-3 and the IGF-I/IGFBP-3 ratio and gain in height.

AIM:Clitoral size references are useful for diagnosing genital abnormalities. Despite the fact that examining the genitalia is an important aspect of newborn evaluation, few studies have been carried out to determine normal clitoral size in newborn infants. The aim of this study was to establish reference values for clitoral size in Nigerian newborn girls and to compare them with references from other ethnic populations. METHODS:A total of 244 healthy newborn girls delivered at 28-43 weeks gestation were enrolled in the study, and clitoral lengths and widths were measured at <72 hours. RESULTS:The mean clitoral length was 7.7 mm with a standard deviation of ±1.37 mm, while the mean clitoral width was 4.40 ± 0.89 mm. The clitoral length was significantly longer than those reported for Caucasian (4.00 ± 1.24 mm), Korean (3.82 ± 1.47), Turkish (4.93 ± 1.61) and Japanese (4.30 ± 1.10) babies. CONCLUSION:The present results make it possible to evaluate clitoral size in Nigerian newborn baby girls in an objective way, to identify genital abnormalities and endocrine disorders. Based on this study, a clitoral length of more than 10 mm would be considered clitoromegaly in a newborn girl in Nigeria.

Allopregnanolone (AP) is an endogenous neurosteroid. It modulates the effect of γ-amino-butyric acid (GABA) on the GABA type A (GABAA) receptor, which leads to increased receptor activity. Since the GABA-system is mainly inhibitory, increased AP activity leads to modulation of neuronal activity. In vitro studies of GABAA receptor activity and in vivo animal studies of sedation have shown that AP-induced effects can be inhibited by another endogenous steroid, namely isoallopregnanolone (ISO). In this study we investigated if ISO can antagonize AP-induced effects in healthy female volunteers, via measurements of saccadic eye velocity (SEV) and self-rated sedation. With a single-blind cross-over design, 12 women were studied on three separate occasions; given AP alone or AP in combination with one of two ISO doses. Congruent with previous reports, AP administration decreased SEV and induced sedation and these effects were diminished by simultaneous ISO administration. Also, the ISO effect modulation was seemingly stronger for SEV than for sedation. These effects were observed already at an ISO dose exposure that was approximately half of that of AP. In conclusion, ISO antagonized AP-induced decrease in SEV and self-reported sedation, probably in a non-competitive manner.

Background/Aims: Growth hormone (GH) treatment regimens do not account for the pubertal increase in endogenous GH secretion. This study assessed whether increasing the GH dose and/or frequency of administration improves pubertal height gain and adult height (AH) in children with low GH secretion during stimulation tests, i.e. idiopathic isolated GH deficiency. Methods: A multicenter, randomized, clinical trial (No. 88-177) followed 111 children (96 boys) at study start from onset of puberty to AH who had received GH 33 µg/kg/day for ≥1 year. They were randomized to receive 67 µg/kg/day (GH67) given as one (GH67×1; n = 35) or two daily injections (GH33×2; n = 36), or to remain on a single 33 µg/kg/day dose (GH33×1; n = 40). Growth was assessed as heightSDSgain for prepubertal, pubertal and total periods, as well as AHSDS versus the population and the midparental height. Results: Pubertal heightSDSgain was greater for patients receiving a high dose (GH67, 0.73) than a low dose (GH33×1, 0.41, p < 0.05). AHSDS was greater on GH67 (GH67×1, -0.84; GH33×2, -0.83) than GH33 (-1.25, p < 0.05), and heightSDSgain was greater on GH67 than GH33 (2.04 and 1.56, respectively; p < 0.01). All groups reached their target heightSDS. Conclusion: Pubertal heightSDSgain and AHSDS were dose dependent, with greater growth being observed for the GH67 than the GH33 randomization group; however, there were no differences between the once- and twice-daily GH67 regimens.

Background: From a population based study of epilepsy in Swedish children a subgroup designated well-functioning with an epilepsy diagnosis in 1997 was worked up from a medical point of view 10 years later.Aim: To describe the psychological and social outcome in this subgroup.Methods: Thirty-one patients aged 11-22 years and their parents/partners responded to a questionnaire according to Achenbach System of Empirically Based Assessment (ASEBA) to evaluate behavioural and emotional problems, and social competence.Results: Active epilepsy, diagnosed in 32%, was related to attention problems, somatic complaints, and school problems. Polytherapy, used in 16%, was related to attention problems and aggressive behaviour. School problems were found in six of seven children younger than 18 years. Internalizing, externalizing, and 'other' syndromes were found in 29% of the individuals, but a grouping of these syndromes in the clinical range only in two (6.5%), a girl with generalized tonic clonic seizures alone, and a boy with structural focal epilepsy. Both had active epilepsy and were treated with polytherapy. All ten individuals with Rolandic epilepsy were classified as normal. The answers to the ASEBA questionnaire of individuals and parents/partners were inconsistent, and parents generally stated more problems than the individuals.Summary.: This 10-year follow-up study of psychological and social outcome in well-functioning children and adolescents with childhood onset epilepsy shows some emotional, behavioural, and social problems. Thus, early information to increase knowledge about epilepsy and associated psychological co-morbidities in order to decrease risk of low self-esteem, social anxiety, and depression later in life is of importance. (C) 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Children participating in longitudinal type 1 diabetes prediction studies were reported to have less severe disease at diabetes diagnosis. Our aim was to investigate children who from birth participated in the Diabetes Prediction in Skåne (DiPiS) study for metabolic status at diagnosis and then continued to be followed for 2 yr of regular clinical care.

CONTEXT:GH treatment significantly increased adult height (AH) in a dose-dependent manner in short non-GH-deficient children in a randomized, controlled, clinical trial; the mean gain in height SD score (heightSDS) was 1.3 (range 0-3), compared with 0.2 in the untreated group.OBJECTIVE:The objective of the study was to analyze the relationship between IGF-1SDS, IGF binding protein-3 SDS (IGFBP3SDS), and their ratioSDS with a gain in the heightSDS until AH in non-GH-deficient short children.DESIGN AND SETTING:This was a randomized, controlled, multicenter clinical trial.INTERVENTION:The intervention included GH treatment: 33 or 67 μg/kg · d plus untreated controls.SUBJECTS:One hundred fifty-one non-GH-deficient short children were included in the intent-to-treat (ITT) population and 108 in the per-protocol (PP) population; 112 children in the ITT and 68 children in the PP populations had idiopathic short stature (ISS).MAIN OUTCOME MEASURES:Increments from baseline to on-treatment study mean IGF-1SDS (ΔIGF-1SDS), IGFBP3SDS, and IGF-1 to IGFBP3 ratioSDS were assessed in relationship to the gain in heightSDS.RESULTS:Sixty-two percent of the variance in the gain in heightSDS in children on GH treatment could be explained by four variables: ΔIGF-1SDS (explaining 28%), bone age delay, birth length (the taller the better), and GH dose (the higher the better). The lower IGF-1SDS was at baseline, the higher was its increment during treatment. For both the AllPP- and the ISSPP-treated groups, the attained IGF-1SDS study level did not correlate with height gain.CONCLUSION:In short non-GH-deficient children, the GH dose-related increment in IGF-1SDS from baseline to mean study level was the most important explanatory variable for long-term growth response from the peripubertal period until AH, when IGF-1SDS, IGFBP3SDS, and their ratioSDS were compared concurrently.

Children with type 1 diabetes (T1D) risk and islet autoantibodies are recruited to a secondary prevention study. The aims were to determine metabolic control in relation to human leukocyte antigen (HLA) genetic risk and islet autoantibodies in prepubertal children.

Environmental factors, including viral infections, may explain an increasing and fluctuating incidence of childhood type 1 diabetes (T1D). Ljungan virus (LV) isolated from bank voles have been implicated, but it is unclear whether LV contributes to islet autoimmunity, progression to clinical onset, or both, of T1D. The aim was to test whether LV antibodies (LVAb) were related to HLA-DQ and islet autoantibodies in newly diagnosed T1D patients (n=676) and controls (n=309). Patients, 0-18 years of age, diagnosed with T1D in 1996-2005 were analyzed for LVAb, HLA-DQ genotypes, and all seven known islet autoantibodies (GADA, IA-2A, IAA, ICA, ZnT8RA, ZnT8WA, and ZnT8QA). LVAb at 75(th) percentile, defined as cut off, was 90 (range 6-3936) U/mL and 4(th) quartile LVAb were found in 25% (170/676) of which 64% were <10 (n=108, p<0.0001), and 27% were<5 (n=45; p<0.0001) years old. The 4(th) quartile LVAb in children <10 years of age correlated to HLA DQ2/8, 8/8, and 8/X (p<0.0001). Furthermore, in the group with 4(th) quartile LVAb, 55% were IAA positive (p=0.01) and correlation was found between 4(th) quartile LVAb and IAA in children <10 years of age (p=0.035). It is concluded that 1) LVAb were common among the young T1D patients and LVAb levels were higher in the younger age groups; 2) 4(th) quartile LVAb correlated with IAA; and 3) there was a correlation between 4(th) quartile LVAb and HLA-DQ8, particularly in the young patients. The presence of LVAb supports the notion that prior exposure to LV may be associated with T1D.

To evaluate the cost-effectiveness of growth hormone (GH) treatment (Genotropin®) compared with no GH treatment in adults with GH deficiency in a Swedish societal setting.

Objective: The role of adipokines in the regulation of energy substrate production in non-diabetic pregnant women has not been elucidated. We hypothesize that serum concentrations of adiponectin are related to fetal growth via maternal fat mass, insulin resistance and glucose production, and further, that serum levels of leptin are associated with lipolysis and that this also influences fetal growth. Hence, we investigated the relationship between adipokines, energy substrate production, insulin resistance, body composition and fetal weight in non-diabetic pregnant women in late gestation.Study design: Twenty pregnant women with normal glucose tolerance were investigated at 36 weeks of gestation at Uppsala University Hospital. Levels of adipokines were related to rates of glucose production and lipolysis, maternal body composition, insulin resistance, resting energy expenditure and estimated fetal weights. Rates of glucose production and lipolysis were estimated by stable isotope dilution technique.Results: Median (range) rate of glucose production was 805 (653-1337) mu mol/min and that of glycerol production, reflecting lipolysis, was 214 (110-576) mu mol/min. HOMA insulin resistance averaged 1.5 +/- 0.75 and estimated fetal weights ranged between 2670 and 4175 g (-0.2 to 2.7 SDS). Mean concentration of adiponectin was 7.2 +/- 2.5 mg/L and median level of leptin was 47.1 (9.9-58.0) mu g/L. Adiponectin concentrations (7.2 +/- 2.5 mg/L) correlated inversely with maternal fat mass, insulin resistance, glucose production and fetal weight, r = -0.50, p < 0.035, r = -0.77, p < 0.001, r = -0.67, p < 0.002, and r = -0.51, p < 0.032, respectively. Leptin concentrations correlated with maternal fat mass and insulin resistance, r = 0.76, p < 0.001 and r = 0.73, p < 0.001, respectively. There was no correlation between niaternal levels of leptin and rate of glucose production or fetal weight. Neither were any correlations found between levels of leptin or adiponectin and maternal lipolysis or resting energy expenditure.Conclusion: The inverse correlations between levels of maternal adiponectin and insulin resistance as well as endogenous glucose production rates indicate that low levels of adiponectin in obese pregnant women may represent one mechanism behind increased fetal size. Maternal levels of leptin are linked to maternal fat mass and its metabolic consequences, but the data indicate that leptin lacks a regulatory role with regard to maternal lipolysis in late pregnancy. (C) 2012 Elsevier Ireland Ltd. All rights reserved.