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BackgroundHeterogeneity in the rate of β-cell loss in newly diagnosed type 1 diabetes patients is poorly understood and creates a barrier to designing and interpreting disease-modifying clinical trials. Integrative analyses of complementary multi-omics data obtained after the diagnosis of T1D may provide mechanistic insight into the diverse rates of disease progression.MethodsWe collected samples in a pan-European consortium that enabled the concerted analysis of five different omics modalities in data from 97 newly diagnosed patients. In this study we used Multi-Omics Factor Analysis to identify molecular signatures correlating with post-diagnosis decline in β-cell mass measured as fasting C-peptide.ResultsTwo molecular signatures were significantly correlated with fasting C-peptide levels. One signature showed a correlation to neutrophil degranulation, cytokine signaling, lymphoid and non-lymphoid cell interactions and G-protein coupled receptor signaling events that were inversely associated with rapid decline in β-cell function. The second signature was related to translation and viral infection were inversely associated with change in β-cell function. In addition, the immunomics data revealed a Natural Killer cell signature associated with rapid β-cell decline.ConclusionFeatures that differ between individuals with slow and rapid decline in β-cell mass could be valuable in staging and prediction of the rate of disease progression and thus enable smarter (shorter and smaller) trial designs for disease modifying therapies, as well as offering biomarkers of therapeutic effect.FundingThis work is funded by the Innovative Medicine Initiative 2 Joint Undertaking (IMI2 JU) under grant agreement N° 115797 (INNODIA) and N° 945268 (INNODIA HARVEST). This Joint Undertaking receives support from the Union’s Horizon 2020 research and innovation program and ‘EFPIA’, ‘JDRF’ and ‘The Leona M. and Harry B. Helmsley Charitable Trust’.

Aims/hypothesis We hypothesised that adolescents with type 1 diabetes with a urinary albumin/creatinine ratio (ACR) in the upper tertile of the normal range (high ACR) are at greater risk of three-step diabetic retinopathy progression (3DR) independent of glycaemic control. Methods This was a prospective observational study in 710 normoalbuminuric adolescents with type 1 diabetes from the non-intervention cohorts of the Adolescent Cardio-Renal Intervention Trial (AdDIT). Participants were classified as ‘high ACR’ or ‘low ACR’ (lowest and middle ACR tertiles) using baseline standardised log10 ACR. The primary outcome, 3DR, was determined from centrally graded, standardised two-field retinal photographs. 3DR risk was determined using multivariable Cox regression for the effect of high ACR, with HbA1c, BP, LDL-cholesterol and BMI as covariates; diabetes duration was the time-dependent variable. Results At baseline mean ± SD age was 14.3 ± 1.6 years and mean ± SD diabetes duration was 7.2 ± 3.3 years. After a median of 3.2 years, 83/710 (12%) had developed 3DR. In multivariable analysis, high ACR (HR 2.1 [1.3, 3.3], p=0.001), higher mean IFCC HbA1c (HR 1.03 [1.01, 1.04], p=0.001) and higher baseline diastolic BP SD score (HR 1.43 [1.08, 1.89], p=0.01) were independently associated with 3DR risk. Conclusions/interpretation High ACR is associated with greater risk of 3DR in adolescents, providing a target for future intervention studies. Trial registration isrctn.org ISRCTN91419926. Graphical abstract

Identifying genetic determinants for longitudinal changes in albumin excretion in individuals with type 1 diabetes may help identify those that are predisposed to renal, retinal and cardiovascular complications. Most studies have focussed on genetic predisposition to diabetic kidney disease and used cross-sectional measurements of urinary albumin excretion, but with limited success. Here, we utilise the wealth of longitudinal data and bio-samples collected from cohorts of childhood-onset type 1 diabetes followed over the last 30 years to describe a novel trajectory phenotype quantifying urinary albumin excretion changes during childhood and adolescence. We conducted a genome-wide association study and fine-mapping analysis for albumin excretion in 1584 individuals, finding one signal for cross-sectional albumin excretion close toGALNTL6(rs150766792), which validated in a previous independent study, and a novel genome-wide significant signal for albumin excretion trajectory in theCDH18gene region (rs145715205). Our trajectory phenotype quantifies albumin progression and offers a complementary measure to an albumin excretion phenotype based on a single measurement (i.e. most recent data collection) or an average of repeated measurements in longitudinal studies. It can be used to identify genetic or other risk factors which predict better or worse prognosis, thus facilitating the development of new preventive and therapeutic approaches.

Peer reviewed: True, The aim of this systematic review was to report the evidence on optimal prandial timing of insulin bolus in youths with type 1 diabetes. A systematic search was performed including studies published in the last 20 years (2002-2022). A PICOS framework was used in the selection process and evidence was assessed using the GRADE system. Up to one third of children and adolescents with type 1 diabetes injected rapid-acting insulin analogues after a meal. Moderate-high level quality studies showed that a pre-meal bolus compared with a bolus given at the start or after the meal was associated with a lower peak blood glucose after one to two hours, particularly after breakfast, as well as with reduced HbA1c, without any difference in the frequency of hypoglycemia. There were no differences related to the timing of bolus in total daily insulin and BMI, although these results were based on a single study. Data on individuals' treatment satisfaction were limited but did not show any effect of timing of bolus on quality of life. In addition, post-prandial administration of fast-acting analogues was superior to rapid-acting analogues on post-prandial glycemia. There was no evidence for any difference in outcomes related to the timing of insulin bolus across age groups in the two studies. In conclusion, prandial insulin injected before a meal, particularly at breakfast, provides better post-prandial glycemia and HbA1c without increasing the risk of hypoglycemia, and without affecting total daily insulin dose and BMI. For young children who often have variable eating behaviors, fast-acting analogues administered at mealtime or post-meal could provide an additional advantage.

An increased albumin-creatinine ratio within the normal range can identify adolescents at higher risk of developing adverse cardio-renal outcomes as they progress into adulthood. Utilizing a parallel randomized controlled trial and observational cohort study, we characterized the progression of vascular phenotypes throughout this important period and investigated the effect of ACE (angiotensin-converting enzyme) inhibitors and statins in high-risk adolescents. Endothelial function (flow-mediated dilation and reactive hyperemia index) and arterial stiffness (carotid-femoral pulse wave velocity) were assessed in 158 high-risk participants recruited to a randomized, double-blind placebo-controlled 2×2 factorial trial (randomized, placebo-controlled trial) of ACE inhibitors and/or statins in adolescents with type 1 diabetes (AdDIT [Adolescent Type 1 Diabetes cardio-renal Intervention Trial]). Identical measures were also assessed in 215 lower-risk individuals recruited to a parallel observational study. In the randomized, placebo-controlled trial, high-risk patients randomized to ACE inhibitors had improved flow-mediated dilation after 2 to 4 years of follow-up (mean [95% CI]: 6.6% [6.0–7.2] versus 5.3% [4.7–5.9]; P =0.005), whereas no effect was observed following statin use (6.2% [5.5–6.8] versus 5.8% [5.1–6.4]; P =0.358). In the observational study, patients classed as high-risk based on albumin-creatinine ratio showed evidence of endothelial dysfunction at the end of follow-up (flow-mediated dilation=4.8% [3.8–5.9] versus 6.3% [5.8–6.7] for high-risk versus low-risk groups; P =0.015). Neither reactive hyperemia index nor pulse wave velocity were affected by either treatment ( P >0.05 for both), but both were found to increase over the duration of follow-up (0.07 [0.03–0.12]; P =0.001 and 0.5 m/s [0.4–0.6]; P Registration— URL: https://www.clinicaltrials.gov ; Unique identifier NCT01581476.

Purpose of review Individuals with type 1 diabetes (T1D) have excess cardiovascular risk and reduced life expectancy. Adolescence is the time when the first signs of vascular complications appear and a critical window for interventions. This article reviews recent evidence on cardiometabolic risk factors and their management in youth with T1D. Recent findings Adolescents with T1D show early signs of vascular complications, as a result of several cardiometabolic risk factors. Poor glycemic control is one of the main risk factors and the main target of treatment. However, only a minority of adolescents with T1D reaches recommended targets for glycemic control. Hypertension, dyslipidemia, smoking, alcohol use, obesity and insulin resistance are other common cardiometabolic risk factors in this age group. Recent data confirm that screening for these risk factors is suboptimal and use of pharmacological interventions for hypertension and dyslipidemia remains low. Data on adjunctive noninsulin agents to improve glycemic control and other cardiometabolic risk factors are still lacking in this age group. Summary Vascular complications and the associated mortality remain a major issue for youth with T1D. Better screening strategies for cardiometabolic risk factors and interventions are required to improve the long-term prognosis of youth with T1D.

AIMS: We aimed to estimate the prevalence of Diabetic peripheral neuropathy (DPN) and Cardiac autonomic neuropathy (CAN) in youth with type 1 diabetes; identify key risk factors; identify the most useful tests for the diagnostic evaluation of DPN and CAN; identify key treatment options for DPN and CAN. METHODS: A systematic search was performed including studies published in the last 15 years. PICO framework was used in the selection process and evidence was assessed using the GRADE system. RESULTS: A total of 758 studies were identified and a final number of 49 studies were included in this systematic review. According to moderate-high level quality studies, the prevalence of probable DPN, ranged between 13.5 and 62%; subclinical DPN between 22 and 88%; confirmed DPN between 2.6 and 11%. The Michigan Neuropathy Screening Instrument was the tool with higher sensitivity and specificity for detecting DPN, which needs to be confirmed by nerve conduction velocity. The prevalence of CAN was 4-39%. Specific treatment options for DPN or CAN in patients younger than 25 years are not available. Key risk factors for DPN and CAN are hyperglycemia/HbA1c, age, diabetes duration, the presence of other microvascular complications, waist/height ratio, lipid profile and blood pressure. For CAN, additional risk factors were cigarette smoking, BMI and total daily insulin. CONCLUSIONS: Prevalence of neuropathy in youth with type 1 diabetes varies depending on different screening methods and characteristics of the study populations. However, the assessed studies confirmed a relatively high prevalence of subclinical neuropathy, reiterating the importance of early identification of risk factors to prevent this complication.

Long-term complications of type 1 diabetes (T1D) include microvascular complications and macrovascular disease. Despite the important advances in the treatment of T1D of the last decades, these complications still represent the leading cause of morbidity and mortality in patients with T1D. Extensive evidence indicates that structural and functional alterations of the kidney, retina, nerves and large arteries occur already in the first years after the onset of diabetes. We performed a comprehensive review of the available evidence on screening, diagnosis, prevention and treatment of vascular complications of T1D. In particular, we focused on three major challenges related to long-term complications of T1D: 1) finding of new biomarkers and diagnostic methods able to identify early signs of complications; 2) identifying specific risk factors for the development of these complications; 3) identifying and implementing new therapeutic strategies able to prevent the development and progression of vascular complications.

• Introduction: Type 1 diabetes (T1D) is a chronic autoimmune disease, characterised by progressive destruction of the insulin-producing β cells of the pancreas. One immunosuppressive agent that has recently shown promise in the treatment of new-onset T1D subjects aged 12-45 years is ATG, Thymoglobuline®, encouraging further exploration in lower age groups. Methods and analysis: MELD-ATG is a phase 2, multi-centre, randomised, double-blind, placebo-controlled, multi-arm parallel-group trial in participants 5-25 years diagnosed with T1D within 3–9 weeks of planned treatment day 1. A total of 114 participants will be recruited sequentially into seven different cohorts with the first cohort of 30 participants being randomised to placebo, 2.5 mg/kg, 1.5 mg/kg, 0.5 mg/kg and 0.1 mg/kg ATG total dose in a 1:1:1:1:1 allocation ratio. The next six cohorts of 12-15 participants will be randomised to placebo, 2.5 mg/kg, and one or two selected middle ATG total doses in a 1:1:1:1 or 1:1:1 allocation ratio, as dependent on the number of middle doses, given intravenously over 2 consecutive days. The primary objective will be to determine the changes in stimulated C-peptide response over the first 2 hours of a mixed meal tolerance test (MMTT) at 12 months for 2.5mg/kg ATG arm versus the placebo. Conditional on finding a significant difference at 2.5 mg/kg, a minimally effective dose will be sought. Secondary objectives include the determination of the effects of a particular ATG treatment dose on 1) stimulated C-peptide, 2) HbA1c, 3) daily insulin dose, 4) time in range by intermittent continuous glucose monitoring (CGM) measures, 5) fasting and stimulated dry blood spot (DBS) C-peptide measurements. Ethics and dissemination: MELD-ATG received first regulatory and ethical approvals in Belgium in September 2020 and from the German and UK regulators as of February 2021. The publication policy is set in the INNODIA grant agreement (www.innodia.eu)., Union’s Horizon 2020 research and innovation program EFPIA JDRF The Leona M. and Harry B. Helmsley Charitable Trust

ImportancePresenting with diabetic ketoacidosis (DKA) at onset of type 1 diabetes (T1D) remains a risk. Following a 2011 systematic review, considerable additional articles have been published, and the review required updating.ObjectiveTo evaluate factors associated with DKA at the onset of T1D among pediatric patients.Evidence ReviewIn this systematic review, PubMed, Embase, Scopus, CINAHL, Web of Science, and article reference lists were searched using the population, intervention, comparison, outcome search strategy for primary research studies on DKA and T1D onset among individuals younger than 18 years that were published from January 2011 to November 2021. These studies were combined with a 2011 systematic review on the same topic. Data were pooled using a random-effects model.FindingsA total of 2565 articles were identified; 149 were included, along with 46 from the previous review (total 195 articles). Thirty-eight factors were identified and examined for their association with DKA at T1D onset. Factors associated with increased risk of DKA were younger age at T1D onset (P P = .004), and family history of T1D (OR, 0.46; 95% CI, 0.37-0.57; P P P P Conclusions and RelevanceIn this study, age younger than 2 years at T1D onset, belonging to an ethnic minority population, delayed diagnosis or misdiagnosis, and presenting during the COVID-19 pandemic were associated with increased risk of DKA. Factors associated with decreased risk of DKA included greater knowledge of key signs or symptoms of DKA, such as a family history of T1D or participation in screening programs. Future work should focus on identifying and implementing strategies related to these factors to reduce risk of DKA among new patients with T1D.

Objectives: To determine differences in body composition and glucose metabolism according to childhood growth outcomes in a population-based sample of children born small for gestational age (SGA). Methods: A single-centre study of 259 children born SGA identified through hospital records and contacted when aged 4–7 years. Questionnaire data on pre/perinatal history and growth parameters during childhood was collected from the parents, and in a subgroup of 150 children face-to-face assessments were performed, including anthropometric parameters, lean and fat mass, blood pressure, fasting glucose, and C-peptide. Results: Based on the questionnaires, few children had formal clinic follow-up of growth, but 7% of the cohort showed a height and weight of 2, p = 0.04), trunk-to-limb fat mass ratio (0.63 ± 0.14 vs. 0.56 ± 0.08, p = 0.002), systolic blood pressure SDS (0.09 ± 0.71 vs. –0.32 ± 0.63, p = 0.008), fasting glucose (4.5 ± 0.5 vs. 4.3 ± 0.5 mmol/L, p = 0.03), and C-peptide (306 ± 116 vs. 256 ± 112 pmol/L, p = 0.08). Among children with weight catch-up growth, those with less height gain had a lower limb lean mass index (4.25 ± 0.48 vs. 4.48 ± 0.56 kg/m2, p = 0.02) and fat mass index (1.57 ± 0.59 vs. 1.83 ± 0.77 kg/m2, p = 0.04). Conclusions: Within this population-based sample of SGA children, catch-up growth in weight was associated with higher abdominal fat mass, blood pressure and glycemia; furthermore, in these children, less height gain was associated with reduced limb lean and fat mass.

Diabetes vascular complications, including cardiovascular disease, diabetic nephropathy and retinopathy, have a negative effect on the long-term prognosis of young people with type 1 diabetes mellitus (T1DM). Poor glycaemic control and consequent increased HbA1c levels are major risk factors for the development of vascular complications. HbA1c levels are the main focus of current management strategies; however, the recommended target is rarely achieved in adolescents. Thus, a clear need exists for improved biomarkers to identify high-risk young people early and to develop new intervention strategies. Evidence is accumulating that early increases in urinary albumin excretion could be predictive of adolescents with T1DM who are at an increased risk of developing vascular complications, independent of HbA1c levels. These findings present an opportunity to move towards the personalized care of adolescents with T1DM, which takes into consideration changes in albumin excretion and other risk factors in addition to HbA1c levels.

Cardiovascular disease (CVD) remains the main cause of morbidity and mortality in individuals with type 1 diabetes (T1D). Adolescence appears to be a critical time for the development of early subclinical manifestations of CVD, with these changes likely driven by a deterioration in glycemic control during the progression through puberty, combined with the emergence of numerous other traditional cardiometabolic risk factors (e.g., hypertension, dyslipidemia, smoking, alcohol use, obesity, etc.) which emerge at this age. Although hemoglobin A1C has long been the primary focus of screening and treatment strategies, glycemic control remains poor in youth with T1D. Furthermore, screening for cardiovascular risk factors—which are often elevated in youth with T1D—is suboptimal, and use of pharmacological interventions for hypertension and dyslipidemia remains low. As such, there is a clear need not only for better screening strategies for CVD risk factors in youth, but also early interventions to reduce these, if future CVD events have to be prevented. Accumulating evidence has recently suggested that early increases in urinary albumin excretion, even within the normal range, may identify adolescents with T1D who are at an increased risk of complications, and results from pharmacological intervention with statins and ACE inhibitors in these individuals have been encouraging. These data join a growing evidence highlighting the need for a whole-life approach to prevention starting from childhood if efforts to improve CVD outcomes and related mortality in T1D are to be maintained.

IntroductionThe Global Platform for the Prevention of Autoimmune Diabetes-SINT1A Study is designed as a randomised, placebo-controlled, double-blind, multicentre, multinational, primary prevention study aiming to assess whether daily administration of Bifidobacterium infantis from age 7 days to 6 weeks until age 12 months to children with elevated genetic risk for type 1 diabetes reduces the cumulative incidence of beta-cell autoantibodies in childhood.Methods and analysisInfants aged 7 days to 6 weeks from Germany, Poland, Belgium, UK and Sweden are eligible for study participation if they have a >10.0% expected risk for developing multiple beta-cell autoantibodies by age 6 years as determined by genetic risk score or family history and HLA genotype. Infants are randomised 1:1 to daily administration of B. infantis EVC001 or placebo until age 12 months and followed for a maximum of 5.5 years thereafter. The primary outcome is the development of persistent confirmed multiple beta-cell autoantibodies. Secondary outcomes are (1) Any persistent confirmed beta-cell autoantibody, defined as at least one confirmed autoantibody in two consecutive samples, including insulin autoantibodies, glutamic acid decarboxylase, islet tyrosine phosphatase 2 or zinc transporter 8, (2) Diabetes, (3) Transglutaminase autoantibodies associated with coeliac disease, (4) Respiratory infection rate in first year of life during supplementation and (5) Safety. Exploratory outcomes include allergy, antibody response to vaccines, alterations of the gut microbiome or blood metabolome, stool pH and calprotectin.Ethics and disseminationThe study was approved by the local ethical committees of the Technical University Munich, Medical Faculty, the Technische Universität Dresden, the Medizinische Hochschule Hannover, the Medical University of Warsaw, EC Research UZ Leuven and the Swedish ethical review authority. The results will be disseminated through peer-reviewed journals and conference presentations and will be openly shared after completion of the study.Trial registration numberNCT04769037.

Microvascular complications of type 1 diabetes, which primarily include diabetic kidney disease, retinopathy, and neuropathy, are characterized by damage to the microvasculature of the kidney, retina, and neurons. The pathogenesis of these complications is multifactorial, and several pathways are implicated. These complications are often silent during their early stages, and once symptoms develop, there might be little to be done to cure them. Thus, there is a strong need for novel biomarkers to identify individuals at risk of microvascular complications at an early stage and guide the implementation of new therapeutic options for preventing their development and progression. Recent advancements in proteomics, metabolomics, and other 'omics' have led to the identification of several potential biomarkers of microvascular complications. However, biomarker discovery has met several challenges and, up to now, there are no new biomarkers that have been implemented into clinical practice. This highlights the need for further work in this area to move towards better diagnostic and prognostic approaches.

Objective To determine the potential role of cardiovascular autonomic dysfunction in the development of renal complications in young people with type 1 diabetes (T1D). Methods In this prospective study, 199 children and adolescents recruited to the Oxford Regional Prospective Study underwent assessment of autonomic function ~5 years after diagnosis, and were subsequently followed with longitudinal assessments of HbA1c and urine albumin-creatinine ratio (ACR) over 8.6 ± 3.4 years. Autonomic function was assessed with 4 standardized tests of cardiovascular reflexes: heart rate (HR) response to (1) Valsalva Maneuver, (2) deep breathing, (3) standing, and (4) blood pressure (BP) response to standing. Linear mixed models were used to assess the association between autonomic parameters and future changes in ACR. Results Independent of HbA1c , each SD increase in HR response to Valsalva Maneuver predicted an ACR increase of 2.16% [95% CI: 0.08; 4.28] per year (P = .04), while each SD increase in diastolic BP response to standing predicted an ACR increase of 2.55% [95% CI: 0.37; 4.77] per year (P = .02). The effect of HR response to standing on ACR reached borderline significance (-2.07% [95% CI: -4.11; 0.01] per year per SD increase, P = .051). Conclusions In this cohort of young people with T1D, enhanced cardiovascular reflexes at baseline predicted future increases in ACR. These results support a potential role for autonomic dysfunction in the pathogenesis of diabetic nephropathy.

Childhood obesity is commonly associated with early signs of endothelial dysfunction, characterized by impairment of insulin signaling and vascular Nitric Oxide (NO) availability. However, the underlying mechanisms remain to be established. Hence, we tested the hypothesis that endothelial insulin-stimulated NO production and availability was impaired and related to Endoplasmic Reticulum (ER) in human umbilical vein endothelial cells (HUVECs) cultured with plasma obtained from pre-pubertal obese (OB) children. OB children (N = 28, age: 8.8 ± 2.2; BMI z-score: 2.15 ± 0.39) showed impaired fasting glucose, insulin and HOMA-IR than normal weight children (CTRL; N = 28, age: 8.8 ± 1.7; BMI z-score: 0.17 ± 0.96). The in vitro experiments showed that OB-plasma significantly impaired endothelial insulin-stimulated NO production and bioavailability compared to CTRL-plasma. In parallel, in HUVECs OB-plasma increased GRP78 and activated PERK, eIF2α, IkBα and ATF6 (all ER stress markers). Moreover, OB-plasma increased NF-κB activation and its nuclear translocation. Notably, all these effects proved to be significantly restored by using PBA and TUDCA, known ER stress inhibitors. Our study demonstrate for the first time that plasma from obese children is able to induce in vitro endothelial insulin resistance, which is characterized by reduced insulin-stimulated NO production and bioavailability, endothelial ER stress and increased NF-κB activation., Graphical abstract Image 1, Highlights • Plasma from obese children induce in vitro endothelial insulin resistance (IR). • The mechanism involved is the reduced insulin-stimulated NO bioavailability. • In this experimental condition ER stress is associated to endothelial IR. • The additional effect is the increased endothelial inflammation.

OBJECTIVE Suboptimal adherence to insulin treatment is a main issue in adolescents with type 1 diabetes. However, to date, there are no available data on adherence to adjunct noninsulin medications in this population. Our aim was to assess adherence to ACE inhibitors and statins and explore potential determinants in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS There were 443 adolescents with type 1 diabetes recruited into the Adolescent Type 1 Diabetes Cardio-Renal Intervention Trial (AdDIT) and exposed to treatment with two oral drugs—an ACE inhibitor and a statin—as well as combinations of both or placebo for 2–4 years. Adherence was assessed every 3 months with the Medication Event Monitoring System (MEMS) and pill count. RESULTS Median adherence during the trial was 80.2% (interquartile range 63.6–91.8) based on MEMS and 85.7% (72.4–92.9) for pill count. Adherence based on MEMS and pill count dropped from 92.9% and 96.3%, respectively, at the first visit to 76.3% and 79.0% at the end of the trial. The percentage of study participants with adherence ≥75% declined from 84% to 53%. A good correlation was found between adherence based on MEMS and pill count (r = 0.82, P < 0.001). Factors associated with adherence were age, glycemic control, and country. CONCLUSIONS We report an overall good adherence to ACE inhibitors and statins during a clinical trial, although there was a clear decline in adherence over time. Older age and suboptimal glycemic control at baseline predicted lower adherence during the trial, and, predictably, reduced adherence was more prevalent in subjects who subsequently dropped out.

Diabetes vascular complications, including cardiovascular disease, diabetic nephropathy and retinopathy, have a negative effect on the long-term prognosis of young people with type 1 diabetes mellitus (T1DM). Poor glycaemic control and consequent increased HbA

Aim Perinatal factors seem to influence the onset of puberty, but there is limited information on the potential effect of large size at birth on pubertal growth. This study evaluated pubertal growth in children born large for gestational age (LGA) compared to children born appropriate for gestational age (AGA). Methods Longitudinal growth data collected from 70 children – 40 AGA and 30 LGA – were analysed. The ages at take-off, peak height velocity, final height and pubertal growth spurts were calculated using the Preece–Baines model I. Results Large for gestational age children showed an earlier age at take-off compared to AGA children (10.1 ± 1.2 versus 11.0 ± 1.4 years, p = 0.007), whereas the age at peak height velocity and at final height was similar. LGA children showed a longer growth spurt duration (2.5 ± 1 versus 1.5 ± 1.2 years, p < 0.001) and total pubertal duration (5.3 ± 1.2 versus 4.6 ± 1.2 years, p = 0.036) than AGA children. Results were similar when stratified by sex. Conclusion Being born LGA was associated with an earlier pubertal take-off and longer growth duration. These unique findings, due to the lack of studies on pubertal growth patterns in LGA children, might lead the way to novel research and a different approach to LGA children at the onset of pubertal growth.

Copyright © 2016 Termedia & Banach Introduction: Egg allergy is one of the most common food allergies in children. Egg white, including ovomucoid (OVM or Gal d 1) and ovalbumin (OVA or Gal d 2), is the major source of allergens. The aim of this study was to assess the role of Gal d 1 and Gal d 2 in predicting the risk of anaphylaxis caused by eggs in children, and to compare this new diagnostic tool with established methods of allergen-specific IgE detection. Material and methods: One hundred and forty-eight children were divided into 2 groups according to a positive (group A, 33 children) or negative (group B, 115 children) history of anaphylaxis after ingestion/contact with eggs. All patients underwent an allergological evaluation by measurements of specific IgE against egg white: Gal d 1 and Gal d 2. Results: Higher levels of Gal d 1, Gal d 2 and IgE against egg white were detected in group A compared to group B (p < 0.001). Although the area under the curve was similar for Gal d 1 and Gal d 2, egg white specific IgE showed a better sensitivity (85%) for a cut-off value ≥ 0.975 kUA/l, while Gal d 1 and Gal d 2 demonstrated a better specificity (90% and 80%, respectively) for cut-off values ≥ 1.460 kUA/l and ≥ 2.310 kUA/l, respectively. Conclusions: Egg white specific IgE showed a similar ability as Gal d 1 and Gal d 2 in differentiating children at risk for egg anaphylaxis, although Gal d 1 and Gal d 2 showed a better specificity.

Aims High-density lipoprotein (HDL) function may be altered in patients with chronic disease, transforming the particle from a beneficial vasoprotective molecule to a noxious pro-inflammatory equivalent. Adolescents with Type 1 diabetes often have elevated HDL, but its vasoprotective properties and relationship to endothelial function have not been assessed. Methods and results Seventy adolescents with Type 1 diabetes (age 10-17 years) and 30 age-matched healthy controls supplied urine samples for the measurement of early renal dysfunction (albumin:creatinine ratio; ACR), blood samples for the assessment of cardiovascular risk factors (lipid profiles, HDL functionality, glycaemic control, and inflammatory risk score), and had their conduit artery endothelial function tested using flow-mediated dilation (FMD). HDL-c levels (1.69 ± 0.41 vs. 1.44 ± 0.29mmol/L; P < 0.001), and glycated haemoglobin (HbA1c) (8.4 ± 1.2 vs. 5.4 ± 0.2%; P < 0.001) were increased in all patients compared with controls. However, increased inflammation and HDL dysfunction were evident only in patients who also had evidence of early renal dysfunction (mean ± standard deviation for high-ACR vs. low-ACR and healthy controls: inflammatory risk score 11.3 ± 2.5 vs. 9.5 ± 2.4 and 9.2 ± 2.4, P < 0.01; HDL-mediated nitric-oxide bioavailability 38.0 ± 8.9 vs. 33.3 ± 7.3 and 25.0 ± 7.7%, P < 0.001; HDL-mediated superoxide production 3.71 ± 3.57 vs. 2.11 ± 3.49 and 1.91 ± 2.47nmol O2 per 250 000 cells, P < 0.05). Endothelial function (FMD) was impaired only in those who had both a high inflammatory risk score and high levels of HDL-c (P < 0.05). Conclusion Increased levels of HDL-c commonly observed in individuals with Type 1 diabetes may be detrimental to endothelial function when accompanied by renal dysfunction and chronic inflammation. © The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.

High-density lipoprotein (HDL) function may be altered in patients with chronic disease, transforming the particle from a beneficial vasoprotective molecule to a noxious pro-inflammatory equivalent. Adolescents with Type 1 diabetes often have elevated HDL, but its vasoprotective properties and relationship to endothelial function have not been assessed.Seventy adolescents with Type 1 diabetes (age 10-17 years) and 30 age-matched healthy controls supplied urine samples for the measurement of early renal dysfunction (albumin:creatinine ratio; ACR), blood samples for the assessment of cardiovascular risk factors (lipid profiles, HDL functionality, glycaemic control, and inflammatory risk score), and had their conduit artery endothelial function tested using flow-mediated dilation (FMD). HDL-c levels (1.69 ± 0.41 vs. 1.44 ± 0.29mmol/L; P 0.001), and glycated haemoglobin (HbA1c) (8.4 ± 1.2 vs. 5.4 ± 0.2%; P 0.001) were increased in all patients compared with controls. However, increased inflammation and HDL dysfunction were evident only in patients who also had evidence of early renal dysfunction (mean ± standard deviation for high-ACR vs. low-ACR and healthy controls: inflammatory risk score 11.3 ± 2.5 vs. 9.5 ± 2.4 and 9.2 ± 2.4, P 0.01; HDL-mediated nitric-oxide bioavailability 38.0 ± 8.9 vs. 33.3 ± 7.3 and 25.0 ± 7.7%, P 0.001; HDL-mediated superoxide production 3.71 ± 3.57 vs. 2.11 ± 3.49 and 1.91 ± 2.47nmol O2 per 250 000 cells, P 0.05). Endothelial function (FMD) was impaired only in those who had both a high inflammatory risk score and high levels of HDL-c (P 0.05).Increased levels of HDL-c commonly observed in individuals with Type 1 diabetes may be detrimental to endothelial function when accompanied by renal dysfunction and chronic inflammation.