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Summary: Background: Closed-loop insulin delivery systems have the potential to address suboptimal glucose control in children and adolescents with type 1 diabetes. We compared safety and efficacy of the Cambridge hybrid closed-loop algorithm with usual care over 6 months in this population. Methods: In a multicentre, multinational, parallel randomised controlled trial, participants aged 6–18 years using insulin pump therapy were recruited at seven UK and five US paediatric diabetes centres. Key inclusion criteria were diagnosis of type 1 diabetes for at least 12 months, insulin pump therapy for at least 3 months, and screening HbA1c levels between 53 and 86 mmol/mol (7·0–10·0%). Using block randomisation and central randomisation software, we randomly assigned participants to either closed-loop insulin delivery (closed-loop group) or to usual care with insulin pump therapy (control group) for 6 months. Randomisation was stratified at each centre by local baseline HbA1c. The Cambridge closed-loop algorithm running on a smartphone was used with either (1) a modified Medtronic 640G pump, Medtronic Guardian 3 sensor, and Medtronic prototype phone enclosure (FlorenceM configuration), or (2) a Sooil Dana RS pump and Dexcom G6 sensor (CamAPS FX configuration). The primary endpoint was change in HbA1c at 6 months combining data from both configurations. The primary analysis was done in all randomised patients (intention to treat). Trial registration ClinicalTrials.gov, NCT02925299. Findings: Of 147 people initially screened, 133 participants (mean age 13·0 years [SD 2·8]; 57% female, 43% male) were randomly assigned to either the closed-loop group (n=65) or the control group (n=68). Mean baseline HbA1c was 8·2% (SD 0·7) in the closed-loop group and 8·3% (0·7) in the control group. At 6 months, HbA1c was lower in the closed-loop group than in the control group (between-group difference −3·5 mmol/mol (95% CI −6·5 to −0·5 [–0·32 percentage points, −0·59 to −0·04]; p=0·023). Closed-loop usage was low with FlorenceM due to failing phone enclosures (median 40% [IQR 26–53]), but consistently high with CamAPS FX (93% [88–96]), impacting efficacy. A total of 155 adverse events occurred after randomisation (67 in the closed-loop group, 88 in the control group), including seven severe hypoglycaemia events (four in the closed-loop group, three in the control group), two diabetic ketoacidosis events (both in the closed-loop group), and two non-treatment-related serious adverse events. There were 23 reportable hyperglycaemia events (11 in the closed-loop group, 12 in the control group), which did not meet criteria for diabetic ketoacidosis. Interpretation: The Cambridge hybrid closed-loop algorithm had an acceptable safety profile, and improved glycaemic control in children and adolescents with type 1 diabetes. To ensure optimal efficacy of the closed-loop system, usage needs to be consistently high, as demonstrated with CamAPS FX. Funding: National Institute of Diabetes and Digestive and Kidney Diseases.

Background: Highly consistent positive associations are reported between infancy growth and later obesity risk. However, it is unclear whether infancy growth parameters beyond body weight add to the prediction of later obesity risk. Aim: To assess whether infancy length and skinfold thicknesses add to infancy weight in the prediction of childhood adiposity. Subjects and methods: This analysis included 254 children with available data on infant growth from birth to 24 months and childhood adiposity at age 6–11 years measured by DXA. Multilevel linear regression was used to examine the predictors of childhood percent body fat (%BF), with adjustment for sex and age at follow-up visit. Results: Birth weight and weight gain (modelled as changes in z-score) between 0–3 months and 3–24 months showed independent positive relationships with childhood %BF. The addition of gains in infant length and skinfolds between 0–3 months, but not 3–24 months, improved overall model prediction, from 18.7% to 20.7% of the variance in childhood %BF (likelihood ratio test, p

BACKGROUND: Aromatase catalyses the conversion of androgens to estrogens and thus variation in the aromatase gene could contribute to female syndromes of androgen excess, such as precocious pubarche (PP) and polycystic ovarian syndrome (PCOS). METHODS: Two groups, one case–control containing girls from Barcelona, Spain with PP (n=186) or healthy controls (n=71), and the other a population study of young women from Oxford, UK, who volunteered for a study of normal women's health (n=109), were genotyped at four aromatase gene haplotype-tag single nucleotide polymorphisms (SNP). Clinical features and hormone concentrations relevant to hyperandrogenism were compared across haplotypes or genotypes. RESULTS: Distributions of aromatase haplotypes (P<0.0001) and aromatase SNP_50 genotype (P=0.001) were significantly different between PP girls and Spanish controls. The AGGG haplotype was associated with an odds ratio (95% confidence interval) of 0.5 (0.3–0.9) (P=0.005) for the presence of PP compared to GAGG. In 84 post-pubertal PP girls, aromatase haplotype was associated with functional ovarian hyperandrogenism (P<0.05), independently of insulin sensitivity. In the Oxford population, SNP_50 was associated with variation in PCOS symptom score (P=0.008) and circulating testosterone concentrations (P=0.02). CONCLUSIONS: This study suggests that common variation at the aromatase gene (and not just rare loss-of-function mutations) is associated with androgen excess in girls and young women. [ABSTRACT FROM AUTHOR]