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The article focuses on the concerns about the environmental endocrine toxicity by endocrine disrupting chemicals, which have captured the attention of many national and international health organizations in Great Britain. In fact, the European Commission has identified endocrine disrupting chemicals as an important public health issue and is currently supporting a number of research initiatives. Coordination of targeted toxicological studies is needed in order to provide several information about the concerns.

The article presents a position statement from the International Society for Pediatric and Adolescent Diabetes (ISPAD) on type 1 diabetes (T1D) in schools. Topics discussed include the importance of the role of schools in effective management of T1D; the emotional burden diabetes places on the students and their families; and the importance of maintaining blood glucose levels to a certain level.

Diabet. Med. Aims Using compartment modelling, we assessed the time delay between blood glucose and sensor glucose measured by the Guardian® RT continuous glucose monitoring system in young subjects with Type 1 diabetes (T1D). Methods Twelve children and adolescents with T1D treated by continuous subcutaneous insulin infusion (male/female 7/5; age 13.1 ± 4.2 years; body mass index 21.9 ± 4.3 kg/m2; mean ± sd) were studied over 19 h in a Clinical Research Facility. Guardian® RT was calibrated every 6 h and sensor glucose measured every 5 min. Reference blood glucose was measured every 15 min using a YSI 2300 STAT Plus Analyser. A population compartment model of sensor glucose–blood glucose kinetics was adopted to estimate the time delay, the calibration scale and the calibration shift. Results The population median of the time delay was 15.8 (interquartile range 15.2, 16.5) min, which was corroborated by correlation analysis between blood glucose and 15-min delayed sensor glucose. The delay has a relatively low intersubject variability, with 95% of individuals predicted to have delays between 10.4 and 24.3 min. Population medians (interquartile range) for the scale and shift are 0.800 (0.777, 0.823) (unitless) and 1.66 (1.47, 1.84) mmol/l, respectively. Conclusions In young subjects with T1D, the total time delay associated with the Guardian® RT system was approximately 15 min. This is twice that expected on physiological grounds, suggesting a 5- to 10-min delay because of data processing. Delays above 25 min are rarely to be observed. [ABSTRACT FROM AUTHOR]

Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes mellitus (TIDM). Mortality is predominantly related to the occurrence of cerebral oedema; only a minority of deaths in DKA are attributed to other causes. Cerebral oedema occurs in about 0.3-1% of all episodes of DKA, and its aetiology, pathophysiology, and ideal method of treatment are poorly understood. There is debate as to whether physicians treating DKA can prevent or predict the occurrence of cerebral oedema, and the appropriate site(s) for children with DKA to be managed. There is agreement that prevention of DKA and reduction of its incidence should be a goal in managing children with diabetes. [ABSTRACT FROM AUTHOR]

The article provides an answer to the question on whether angiotensin converting enzyme inhibitors should be used in children with type 1 diabetes and microalbuminuria.

Study Question: Are maternal serum phthalate metabolite, phenol and paraben concentrations measured at 10-17 weeks of gestation associated with male infant genital developmental outcomes, specifically cryptorchidism, anogenital distance (AGD), penile length and testicular descent distance, at birth and postnatally?Summary Answer: Maternal serum bisphenol A (BPA) concentration at 10-17 weeks of gestation was positively associated with congenital or postnatally acquired cryptorchidism, and n-propyl paraben (n-PrP) concentration was associated with shorter AGD from birth to 24 months of age.What Is Known Already: Male reproductive disorders are increasing in prevalence, which may reflect environmental influences on foetal testicular development. Animal studies have implicated phthalates, BPA and parabens, to which humans are ubiquitously exposed. However, epidemiological studies have generated conflicting results and have often been limited by small sample size and/or measurement of chemical exposures outside the most relevant developmental window.Study Design, Size, Duration: Case-control study of cryptorchidism nested within a prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at 10-17 postmenstrual weeks of gestation from a single UK maternity unit between 2001 and 2009 and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 330 mothers of 334 male infants (30 with congenital cryptorchidism, 25 with postnatally acquired cryptorchidism and 279 unmatched controls) were included in the present analysis.Participants/materials, Setting, Methods: Maternal blood was collected at enrolment, and serum levels of 16 phthalate metabolites, 9 phenols (including BPA) and 6 parabens were measured using liquid chromatography/tandem mass spectrometry. Logistic regression was used to model the association of cryptorchidism with serum chemical concentrations, adjusting for putative confounders. Additionally, offspring AGD, penile length and testicular descent distance were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between serum chemical levels and these outcomes were tested using linear mixed models.Main Results and the Role Of Chance: Maternal serum BPA concentration was associated with offspring all-type cryptorchidism both when considered as a continuous exposure (adjusted odds ratio per log10 μg/l: 2.90, 95% CI 1.31-6.43, P =  0.009) and as quartiles (phet =  0.002). Detection of n-PrP in maternal serum was associated with shorter AGD (by 0.242 standard deviations, 95% CI 0.051-0.433, P =  0.01) from birth to 24 months of age; this reduction was independent of body size and other putative confounders. We did not find any consistent associations with offspring outcomes for the other phenols, parabens, and phthalate metabolites measured.Limitations, Reasons For Caution: We cannot discount confounding by other demographic factors or endocrine-disrupting chemicals. There may have been misclassification of chemical exposure due to use of single serum measurements. The cohort was not fully representative of pregnant women in the UK, particularly in terms of smoking prevalence and maternal ethnicity.Wider Implications Of the Findings: Our observational findings support experimental evidence that intrauterine exposure to BPA and n-PrP during early gestation may adversely affect male reproductive development. More evidence is required before specific public health recommendations can be made.Study Funding/competing Interest(s): This work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), Newlife the Charity for Disabled Children, the Mothercare Group Foundation, Mead Johnson Nutrition and the National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre. Visiting Fellowship (J.M.): Regional Programme 'Jiménez de la Espada' for Research Mobility, Cooperation and Internationalization, Seneca Foundation-Science and Technology Agency for the Region of Murcia (No. 20136/EE/17). K.O. is supported by the Medical Research Council (UK) (Unit Programme number: MC_UU_12015/2). The authors declare no conflict of interest. [ABSTRACT FROM AUTHOR]

Study Question: What is the relationship between maternal paracetamol intake during the masculinisation programming window (MPW, 8-14 weeks of gestation) and male infant anogenital distance (AGD), a biomarker for androgen action during the MPW?Summary Answer: Intrauterine paracetamol exposure during 8-14 weeks of gestation is associated with shorter AGD from birth to 24 months of age.What Is Already Known: The increasing prevalence of male reproductive disorders may reflect environmental influences on foetal testicular development during the MPW. Animal and human xenograft studies have demonstrated that paracetamol reduces foetal testicular testosterone production, consistent with reported epidemiological associations between prenatal paracetamol exposure and cryptorchidism.Study Design, Size, Duration: Prospective cohort study (Cambridge Baby Growth Study), with recruitment of pregnant women at ~12 post-menstrual weeks of gestation from a single UK maternity unit between 2001 and 2009, and 24 months of infant follow-up. Of 2229 recruited women, 1640 continued with the infancy study after delivery, of whom 676 delivered male infants and completed a medicine consumption questionnaire.Participants/materials, Setting, Method: Mothers self-reported medicine consumption during pregnancy by a questionnaire administered during the perinatal period. Infant AGD (measured from 2006 onwards), penile length and testicular descent were assessed at 0, 3, 12, 18 and 24 months of age, and age-specific Z scores were calculated. Associations between paracetamol intake during three gestational periods (<8 weeks, 8-14 weeks and >14 weeks) and these outcomes were tested by linear mixed models. Two hundred and twenty-five (33%) of six hundred and eighty-one male infants were exposed to paracetamol during pregnancy, of whom sixty-eight were reported to be exposed during 8-14 weeks. AGD measurements were available for 434 male infants.Main Results and the Role Of Chance: Paracetamol exposure during 8-14 weeks of gestation, but not any other period, was associated with shorter AGD (by 0.27 SD, 95% CI 0.06-0.48, P = 0.014) from birth to 24 months of age. This reduction was independent of body size. Paracetamol exposure was not related to penile length or testicular descent.Limitations, Reasons For Caution: Confounding by other drugs or endocrine-disrupting chemicals cannot be discounted. The cohort was not fully representative of pregnant women in the UK, particularly in terms of maternal ethnicity and smoking prevalence. There is likely to have been misclassification of paracetamol exposure due to recall error.Wider Implications Of the Findings: Our observational findings support experimental evidence that intrauterine paracetamol exposure during the MPW may adversely affect male reproductive development.Study Funding/competing Interests: This work was supported by a European Union Framework V programme, the World Cancer Research Fund International, the Medical Research Council (UK), the Newlife Foundation for Disabled Children, the Evelyn Trust, the Mothercare Group Foundation, Mead Johnson Nutrition, and the National Institute for Health Research Cambridge Comprehensive Biomedical Research Centre. The authors declare no conflict of interest. [ABSTRACT FROM AUTHOR]

Abnormal foetal testis development has been proposed to underlie common disorders of the male reproductive system such as cryptorchidism, hypospadias, reduced semen quality and testicular germ cell tumour, which are regarded as components of a 'testicular dysgenesis syndrome'. The increasing trends and geographical variation in their incidence have been suggested to result from in utero exposure to environmental chemicals acting as endocrine disruptors. In rodents, the anogenital distance ( AGD), measured from the anus to the base of genital tubercle, is a sensitive biomarker of androgen exposure during a critical embryonic window of testis development. In humans, several epidemiological studies have shown alterations in AGD associated with prenatal exposure to several chemicals with potential endocrine disrupting activity. However, the link between AGD and androgen exposure in humans is not well-defined. This review focuses on the current evidence for such a relationship. As in rodents, a clear gender difference is detected during foetal development of the AGD in humans which is maintained thereafter. Reduced AGD in association with clinically relevant outcomes of potential environmental exposures, such as cryptorchidism or hypospadias, is in keeping with AGD as a marker of foetal testicular function. Furthermore, AGD may reflect variations in prenatal androgen exposure in healthy children as shorter AGD at birth is associated with reduced masculine play behaviour in preschool boys. Several studies provide evidence linking shorter AGD with lower fertility, semen quality and testosterone levels in selected groups of adults attending andrology clinics. Overall, the observational data in humans are consistent with experimental studies in animals and support the use of AGD as a biomarker of foetal androgen exposure. Future studies evaluating AGD in relation to reproductive hormones in both infants and adults, and to gene polymorphisms, will help to further delineate the effect of prenatal and postnatal androgen exposures on AGD. [ABSTRACT FROM AUTHOR]

Aims To evaluate safety, efficacy and glucose turnover during closed-loop with meal announcement using reduced prandial insulin boluses in adolescents with type 1 diabetes ( T1D). Methods We conducted a randomized crossover study comparing closed-loop therapy with standard prandial insulin boluses versus closed-loop therapy with prandial boluses reduced by 25%. Eight adolescents with T1D [3 males; mean (standard deviation) age 15.9 (1.5) years, glycated haemoglobin 74 (17) mmol/mol; median (interquartile range) total daily dose 0.9 (0.7, 1.1) IU/kg/day] were studied on two 36-h-long visits. In random order, subjects received closed-loop therapy with either standard or reduced insulin boluses administered with main meals (50-80 g carbohydrates) but not with snacks (15-30 g carbohydrates). Stable-label tracer dilution methodology measured total glucose appearance ( Ra_total) and glucose disposal ( Rd). Results The median (interquartile range) time spent in target (3.9-10 mmol/l) was similar between the two interventions [74 (66, 84)% vs 80 (65, 96)%; p = 0.87] as was time spent above 10 mmol/l [21.8 (16.3, 33.5)% vs 18.0 (4.1, 34.2)%; p = 0.87] and below 3.9 mmol/l [0 (0, 1.5)% vs 0 (0, 1.8)%; p = 0.88]. Mean plasma glucose was identical during the two interventions [8.4 (0.9) mmol/l; p = 0.98]. Hypoglycaemia occurred once 1.5 h post-meal during closed-loop therapy with standard bolus. Overall insulin delivery was lower with reduced prandial boluses [61.9 (55.2, 75.0) vs 72.5 (63.6, 80.3) IU; p = 0.01] and resulted in lower mean plasma insulin concentration [186 (171, 260) vs 252 (198, 336) pmol/l; p = 0.002]. Lower plasma insulin was also documented overnight [160 (136, 192) vs 191 (133, 252) pmol/l; p = 0.01, pooled nights]. Ra_total was similar [26.3 (21.9, 28.0) vs 25.4 (21.0, 29.2) µmol/kg/min; p = 0.19] during the two interventions as was Rd [25.8 (21.0, 26.9) vs 25.2 (21.2, 28.8) µmol/kg/min; p = 0.46]. Conclusions A 25% reduction in prandial boluses during closed-loop therapy maintains similar glucose control in adolescents with T1D whilst lowering overall plasma insulin levels. It remains unclear whether closed-loop therapy with a 25% reduction in prandial boluses would prevent postprandial hypoglycaemia. [ABSTRACT FROM AUTHOR]

Background: The feasibility, safety, and efficacy of prolonged use of an artificial beta cell (closed-loop insulin-delivery system) in the home setting have not been established.Methods: In two multicenter, crossover, randomized, controlled studies conducted under free-living home conditions, we compared closed-loop insulin delivery with sensor-augmented pump therapy in 58 patients with type 1 diabetes. The closed-loop system was used day and night by 33 adults and overnight by 25 children and adolescents. Participants used the closed-loop system for a 12-week period and sensor-augmented pump therapy (control) for a similar period. The primary end point was the proportion of time that the glucose level was between 70 mg and 180 mg per deciliter for adults and between 70 mg and 145 mg per deciliter for children and adolescents.Results: Among adults, the proportion of time that the glucose level was in the target range was 11.0 percentage points (95% confidence interval [CI], 8.1 to 13.8) greater with the use of the closed-loop system day and night than with control therapy (P<0.001). The mean glucose level was lower during the closed-loop phase than during the control phase (difference, -11 mg per deciliter; 95% CI, -17 to -6; P<0.001), as were the area under the curve for the period when the glucose level was less than 63 mg per deciliter (39% lower; 95% CI, 24 to 51; P<0.001) and the mean glycated hemoglobin level (difference, -0.3%; 95% CI, -0.5 to -0.1; P=0.002). Among children and adolescents, the proportion of time with the nighttime glucose level in the target range was higher during the closed-loop phase than during the control phase (by 24.7 percentage points; 95% CI, 20.6 to 28.7; P<0.001), and the mean nighttime glucose level was lower (difference, -29 mg per deciliter; 95% CI, -39 to -20; P<0.001). The area under the curve for the period in which the day-and-night glucose levels were less than 63 mg per deciliter was lower by 42% (95% CI, 4 to 65; P=0.03). Three severe hypoglycemic episodes occurred during the closed-loop phase when the closed-loop system was not in use.Conclusions: Among patients with type 1 diabetes, 12-week use of a closed-loop system, as compared with sensor-augmented pump therapy, improved glucose control, reduced hypoglycemia, and, in adults, resulted in a lower glycated hemoglobin level. (Funded by the JDRF and others; AP@home04 and APCam08 ClinicalTrials.gov numbers, NCT01961622 and NCT01778348.). [ABSTRACT FROM AUTHOR]

The triple-tracer (TT) dilution technique has been proposed to be the gold standard method to measure postprandial glucose appearance. However, validation against an independent standard has been missing. We addressed this issue and also validated the simpler dual-tracer (DT) technique. Sixteen young subjects with type 1 diabetes (age 19.5 ± 3.8 yr, BMI 23.4 ± 1.5 kg/m2, HbA1c 8.7 ± 1.7%, diabetes duration 9.0 ± 6.9 yr, total daily insulin 0.9 ± 0.2 U kg-1 day-1, mean ± SD) received a variable intravenous 20% dextrose infusion enriched with [U-13C]glucose over 8 h to achieve postprandial-resembling glucose excursions while intravenous insulin was administered to achieve postprandialresembling levels of plasma insulin. Primed [6,6-2H2]glucose was infused in a manner that mimicked the expected endogenous glucose production and [U-13C; 1,2,3,4,5,6,6-2H7]glucose was infused in a manner that mimicked the expected glucose appearance from a standard meal. Plasma glucose enrichment was measured by gas chromatography- mass spectrometry. The intravenous dextrose infusion served as an independent standard and was reconstructed using the TT and DT techniques with the two-compartment Radziuk/Mari model and an advanced stochastic computational method. The difference between the infused and reconstructed dextrose profile was similar for the two methods (root mean square error 6.6 ± 1.9 vs. 8.0 ± 3.5 μmol kg-1 min-1, TT vs. DT, P = NS, paired t-test). The TT technique was more accurate in recovering the overall dextrose infusion (100 ± 9 and 92 ± 12%; P = 0.02). The root mean square error associated with the mean dextrose infusion profile was 2.5 and 3.3 μmol kg-1 min-1 for the TT and DT techniques, respectively. We conclude that the TT and DT techniques combined with the advanced computational method can measure accurately exogenous glucose appearance. The TT technique tends to outperform slightly the DT technique, but the latter benefits from reduced experimental and computational complexity. [ABSTRACT FROM AUTHOR]

Background: As most children with acute lymphoblastic leukaemia (ALL) achieve long-term survival, minimising late effects of treatment is a priority. Acute lymphoblastic leukaemia survivors treated historically with protocols including cranial irradiation demonstrate increased weight gain.Methods: We retrospectively studied all 134 patients treated on the MRC/UKALL97 protocol (without cranial irradiation as standard therapy) at a single centre, with 77 inclusions. Height-, weight- and body mass index (BMI) standard-deviation scores (SDS) were recorded at diagnosis and annually until 3 years out (YO) from end of treatment (EoT); changes across time were explored using a univariate model (significance P ≤ 0.001 to account for multiple comparisons).Results: Whole-group height SDS was lower from 1 year into treatment until 2 YO, whereas weight- and BMI-SDS remained higher until 3 YO. In females, height-SDS was lower until EoT, but higher weight- and BMI-SDS persisted until 3 YO. In males, height-SDS was lower at EoT and at 2 YO; differences in BMI-SDS had resolved by 2 YO. By WHO criteria, more patients were overweight or obese at 3 YO than at diagnosis (P=0.01).Conclusion: Survivors of childhood ALL, particularly females, exhibit adverse changes in height-, weight- and BMI-SDS, which arise during treatment and persist into follow-up. Patients should be supported with appropriate dietary and lifestyle advice during ALL treatment and follow-up, which may minimise these changes and reduce associated long-term morbidity. [ABSTRACT FROM AUTHOR]

Diabet. Med. 27, 480–484 (2010) Aims We assessed an extended interruption of subcutaneous insulin delivery during overnight closed-loop glucose control in children and adolescents with Type 1 diabetes (T1D). Methods In seven young subjects with T1D [age 14.2 ± 2.1 years, diabetes duration 6.9 ± 4.0 years, glycated haemoglobin (HbA1c) 8.0 ± 1.5%, body mass index (BMI) 21.4 ± 4.0 kg/m2, total daily insulin dose 0.9 ± 0.2 units/kg/day; mean ± sd) participating in overnight closed-loop glucose control studies, insulin delivery was interrupted for at least 90 min on the basis of predicted hypoglycaemia, low prevailing glucose levels or a too-steep decline in glucose levels. Results Insulin delivery was interrupted for 165 (105, 210) min [median, interquartile range (IQR)]. Plasma glucose was 6.2 ± 3.2 mmol/l at the time of interruption and 5.5 ± 2.0 mmol/l 105 min later ( P = 0.15, paired t-test). Plasma glucose declined during the first hour of the interruption at a rate of 0.02 ± 0.03 mmol/l per min and reached a nadir of 5.2 ± 2.7 mmol/l; 105 min after the interruption, plasma glucose was increasing at a rate of 0.01 ± 0.03 mmol/l per min. When insulin delivery restarted, plasma glucose was 6.4 ± 2.2 mmol/l and peaked at 7.9 ± 2.1 mmol/l in 60 min ( P = 0.01). Physiological levels of plasma insulin were measured throughout with a nadir of 119 ± 78 pmol/l. Conclusions A prolonged interruption of insulin delivery during overnight closed-loop glucose control to prevent hypoglycaemia was not associated with an increased risk of hyperglycaemia in young people with T1D. [ABSTRACT FROM AUTHOR]

Background Reduced insulin sensitivity and increased fat mass have been reported in children and adults with congenital adrenal hyperplasia (CAH). To understand the potential mechanisms underlying these differences, we assessed insulin sensitivity and body composition in children with classical or nonclassical (late-presenting) CAH compared with normal controls. Subjects and methods Thirty-seven children with CAH (26 classical and 11 nonclassical) median (range) age 9·4 year (0·5–15·8) were compared with 41 healthy control children age 11·0 year (3·2–17·1). All children had an overnight fasting blood sample and body composition assessed by DEXA. Pubertal children (14 CAH and 19 controls) also had an oral glucose tolerance test. Classical and nonclassical CAH groups were each compared with controls, adjusting for age, gender and pubertal status. Results Classical CAH children had more fat mass than controls ( P = 0·03), while nonclassical CAH children had more lean mass ( P = 0·006) and higher systolic blood pressure ( P = 0·003) than control children. Among pubertal children, nonclassical CAH children had higher mean insulin (0–120 min; P = 0·04), stimulated insulin (0–30 min; P = 0·02), 120 min insulin ( P = 0·004) and 120 min glucose levels ( P = 0·03) than controls, but no difference in disposition index. Discussion Greater body fat in classical (early-presenting) CAH children could reflect the effects of lifetime glucocorticoid therapy. In contrast, the greater lean mass and parameters of insulin resistance in nonclassical (late-presenting) CAH children likely indicate the adverse metabolic effects of prolonged postnatal androgen excess. [ABSTRACT FROM AUTHOR]

Aims The long-acting insulin analogue glargine reduces nocturnal hypoglycaemia and stabilizes morning blood glucose levels in patients with Type 1 diabetes (T1DM) on multiple injection therapy. However, young children may not tolerate such intensive insulin regimens. We investigated the effects of glargine in various three-injections-daily insulin combinations on 24-h glucose control in prepubertal children. Methods Seventeen T1DM prepubertal children (10 boys), median age 10.2 years (range 6.0–12.4), glycated haemoglobin (HbA1c) 8.8% (6.8–11.5) were recruited to a randomized, open-label, cross-over study. After a 2-week run-in period (with NPH pre-bed), every child underwent three different 3-week treatment blocks in random order. All treatment blocks included glargine pre-bed, but used different morning insulins: block 1, soluble only; block 2, soluble + NPH; block 3, aspart + NPH. Continuous glucose monitoring was performed for 3 days at the end of the run-in and each treatment block. Results Compared with the run-in period on NPH, the three glargine treatment blocks were associated with lower ( P < 0.0001) and less variable ( P < 0.05) pre-breakfast glucose levels, and with an 8–15% reduction in total daily insulin dose ( P < 0.0001). Risk of nocturnal hypoglycaemia detected by continuous glucose monitoring varied significantly between the three glargine treatment blocks, and was lowest when children were given aspart + NPH in the morning (block 3). Conclusion Insulin glargine pre-bed can be used in three-injections-daily regimens in prepubertal children to lower and stabilize pre-breakfast glucose levels. However, to avoid the risk of nocturnal hypoglycaemia, the pre-bed glargine dose should be lowered by giving a further long-acting insulin, such as NPH, in the morning. [ABSTRACT FROM AUTHOR]

Abstract Aims The long duration of action of soluble insulin given in the evening could contribute to the high prevalence of nocturnal hypoglycaemia seen in young children with Type 1 diabetes mellitus (T1DM). We examined whether replacing soluble insulin with insulin lispro reduced this risk in children on a three times daily insulin regimen. Methods Open crossover study comparing insulin lispro vs. soluble insulin in 23 (16 boys) prepubertal children (age 7–11 years) with T1DM on three injections/day; long-acting isophane insulin remained identical. At the end of each 4-month treatment arm, an overnight 15-min venous sampled blood glucose profile was performed. Results Despite similar blood glucose levels pre-evening meal (lispro vs. soluble: mean ± se 6.5 ± 1.0 vs. 7.1 ± 1.1 mmol/l, P = 0.5), post-meal (18.00–22.00 h) blood glucose levels were lower on insulin lispro (area under curve 138 ± 12 vs. 170 ± 13 mmol min-1 l-1 , P = 0.03). In contrast, in the early night (22.00–04.00 h) the prevalence of low blood glucose levels (< 3.5 mmol/l) was lower on lispro (8% of blood glucose levels) than on soluble insulin (13%, P = 0.01). In the early morning (04.00–07.00 h) mean blood glucose and prevalence of low levels were no different between the two treatment groups, and fasting (07.00 h) blood glucose levels were similar (6.1 ± 0.8 vs. 6.3 ± 0.9 mmol/l, P = 0.8). At the end of each treatment arm there were no differences in HbA1c (lispro vs. soluble 8.6% vs. 8.4%, P = 0.3), or in insulin doses (mean, range 0.97, 0.68–1.26 vs. 0.96, 0.53–1.22 U/kg per day, P = 0.2). Conclusions The shorter duration of action of insulin lispro given before the evening meal may reduce the prevalence of early nocturnal hypoglycaemia without compromising HbA1c in young children with T1DM. [ABSTRACT FROM AUTHOR]

Background: Soft tissue measurements from the hand reveal lower second to fourth finger digit ratios (2D:4D) in males compared with females. The relatively longer 4th finger observed in males may be related to increased fetal exposure to androgens influencing the expression of Hox genes.Methods: We have measured 2D:4D ratios in 69 healthy females [median age 9.3 (range 1.9-17) years], 77 control males [median age 13.86 (2.1-20.3) years] and in 66 females with classical virilizing congenital adrenal hyperplasia (CAH) (median age 8.5 (1.1-16.2) years] who are known to be exposed to high concentrations of androgens in utero. Measurements were determined from X-rays of the left hand using vernier callipers. Intra-observer variability in measurement technique was 0.01%.Results: Control males had a significantly lower mean (SD) 2D:4D ratio [0.918 (0.029)] compared with female patients [0.927 (0.029), ANOVA P = 0.02]. No difference in 2D:4D ratio was observed between CAH females [0.925 (0.021)] and control females [0.927 (0.029)]. In contrast, 2D:4D ratio in males were significantly lower compared with CAH females (P = 0.03).Conclusions: 2D:4D ratios determined directly from radiographs of the left hand confirm significant differences between males and females. However, female patients with virilizing CAH do not have a male digit ratio pattern suggesting that in the left hand digit ratio development is not influenced by in-utero exposure to androgens. [ABSTRACT FROM AUTHOR]

Concordance with growth hormone (GH) therapy in 75 children was objectively assessed using data on GP prescriptions over 12 months. 23% missed >2 injections! week. Lower concordance was associated with longer duration on GH therapy (p<0.005), lack of choice of delivery device (p<0.005) and short prescription durations (p<0.005), and predicted lower height velocities (p<0.05). [ABSTRACT FROM AUTHOR]