European Society For Paediatric Endocrinology Research Articles

Managing Children and Adolescents with Type 1 Diabetes and Coexisting Celiac Disease: Real-World Data from a Global Survey.

Celiac disease (CD) is among the diseases most commonly associated with type 1 diabetes (T1D). This study aimed to evaluate the worldwide practices and attitudes of physicians involved in pediatric diabetes care regarding diagnosing and managing CD in children with T1D. The 30-item survey was conducted between July and December 2023 aimed at targeting pediatricians with special interest in T1D and CD. It was shared by the JENIOUS - young investigators group of the International Society of Pediatric and Adolescent Diabetes (ISPAD) - and the YES - early career group of the European Society for Pediatric Endocrinology (ESPE). Overall, 180 physicians (67.8% female) from 25 countries responded. Among respondents, 62.2% expected sustaining optimal glycemic control in children with T1D and CD (T1D + CD) to be more difficult than in children with T1D alone. Majority (81.1%) agreed that more specific guidelines are needed. The follow-up routine for patients with T1D + CD differed, and one-quarter of physicians scheduled more frequent follow-up checkups for these patients. Seventy percent agreed multidisciplinary outpatient clinics for their follow-up is needed. In the multivariate ordinal logistic regression model, a statistically significant predictor of a higher degree of practice according to ISPAD 2022 guidelines was a higher level of country income (OR = 3.34; p < 0.001). These results showed variations in physicians' practices regarding managing CD in children with T1D, emphasizing the need for more specific guidelines and intensive education of physicians in managing this population, especially in lower-income countries. Our data also suggest the implementation of multidisciplinary outpatient clinics for their follow-up.

Clinical practice guidelines for the care of girls and women with Turner syndrome.

Turner syndrome (TS) affects 50 per 100 000 females. TS affects multiple organs through all stages of life, necessitating multidisciplinary care. This guideline extends previous ones and includes important new advances, within diagnostics and genetics, estrogen treatment, fertility, co-morbidities, and neurocognition and neuropsychology. Exploratory meetings were held in 2021 in Europe and United States culminating with a consensus meeting in Aarhus, Denmark in June 2023. Prior to this, eight groups addressed important areas in TS care: (1) diagnosis and genetics, (2) growth, (3) puberty and estrogen treatment, (4) cardiovascular health, (5) transition, (6) fertility assessment, monitoring, and counselling, (7) health surveillance for comorbidities throughout the lifespan, and (8) neurocognition and its implications for mental health and well-being. Each group produced proposals for the present guidelines, which were meticulously discussed by the entire group. Four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with systematic review of the literature. The guidelines project was initiated by the European Society for Endocrinology and the Pediatric Endocrine Society, in collaboration with members from the European Society for Pediatric Endocrinology, the European Society of Human Reproduction and Embryology, the European Reference Network on Rare Endocrine Conditions, the Society for Endocrinology, and the European Society of Cardiology, Japanese Society for Pediatric Endocrinology, Australia and New Zealand Society for Pediatric Endocrinology and Diabetes, Latin American Society for Pediatric Endocrinology, Arab Society for Pediatric Endocrinology and Diabetes, and the Asia Pacific Pediatric Endocrine Society. Advocacy groups appointed representatives for pre-meeting discussions and the consensus meeting.

Comparison of WHO 2006 Growth Standards and Synthetic Indian References in Assessing Growth in Normal Children and Children with Growth-Related Disorders.

A good screening tool, such as a growth chart, should distinguish between children with normal growth and those with perturbed growth. Suitability of synthetic Indian growth references for diagnosing growth-related disorders for under-five children has not been evaluated. To assess the validity of World Health Organization (WHO) 2006 standards vs synthetic Indian references (2019) (by comparing weight, height, body mass index (BMI), standard deviation scores (SDS) and the composite index of anthropometric failure (CIAF)) in differentiating normal children and children with growth-related disorders. Records of 2188 children (0-60 months) attending a tertiary centre paediatric outpatient department (OPD) were retrospectively studied; 1854 children were healthy and 334 were diagnosed with growth-related disorders as per the European Society for Paediatric Endocrinology (ESPE) classification. The anthropometric parameters converted to Z-scores for weight-for-age (WAZ), height-for-age (HAZ), BMI-for-age (BAZ) and a CIAF were computed using WHO and synthetic charts; Student's t-test was used for assessing differences and Youden's index for validity. Disease status of children and anthropometric failure on WAZ, HAZ, BAZ and CIAF on both WHO and synthetic charts had a significant association (P-value <0.05). WAZ, HAZ on both charts and CIAF on synthetic chart had a fair to moderate agreement (Kappa statistics) with disease status as per diagnosis (P-value <0.05). The sensitivity and negative predictive value for all anthropometric parameters were higher for synthetic charts. Indian charts were more sensitive for diagnosing growth-related disorders from birth to 60 months of age when compared to WHO growth standards.

Klinefelter: Which Sexuality?

Klinefelter syndrome (KS) was described by Klinefelter, Reifenstein, and Albright in 1942, who described 9 adult males with gynecomastia, small and firm testes, azoospermia, and increased serum FSH with functional Leydig cells. In 1959, using cytogenetics, Jacobs and Strong described the existence of an extra X chromosome in a male with Klinefelter syndrome The International Consensus Conference organized by the Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology in 2006 included KS in disorders of sexual development. Klinefelter syndrome is also characterized by a genetic dysfunction of the entire gonad that affects germ cells from early fetal life and Sertoli and Leydig cells from mid-puberty. Today we know much more. In this article, we have delved into the social, relational, and sexual quality of life of patients with KS, going beyond fertility studies.

X-Linked Hypophosphatemia at the European Society of Pediatric Endocrinology Meeting 2022

AbstractRickets, a growth plate disorder, is classified into calcipenic and phosphopenic types based on the etiology. Phosphopenic rickets can be further classified into fibroblast growth factor 23 (FGF23) mediated and non-FGF23 mediated. FGF-23 has a phosphaturic effect which results in hypophosphatemia and, therefore, the accumulation of hypertrophied chondrocytes, leading to rachitic changes in the bones. One of the most common causes of inherited hypophosphatemic rickets is X-linked hypophosphatemia (XLH), mainly due to a mutation in the PHEX gene that ends in the extended release of FGF-23. During the 60th annual meeting of the European Society for Pediatric Endocrinology, held in Rome between September 15 and 19, 2022, approximately 15 presentations were made either as free communication or poster. In addition, there was a dedicated satellite symposium focusing on XLH. This article has been prepared mainly to share knowledge and updates discussed during the meeting about hypophosphatemic rickets, as we feel this disease is still to be focused on in the MENA region, since there are some gaps in the recognition and management of FGF23 hypophosphatemic rickets and osteomalacia.

Pubertal induction and transition to adult sex hormone replacement in patients with congenital pituitary or gonadal reproductive hormone deficiency: an Endo-ERN clinical practice guideline

An Endo-European Reference Network guideline initiative was launched including 16 clinicians experienced in endocrinology, pediatric and adult and 2 patient representatives. The guideline was endorsed by the European Society for Pediatric Endocrinology, the European Society for Endocrinology and the European Academy of Andrology. The aim was to create practice guidelines for clinical assessment and puberty induction in individuals with congenital pituitary or gonadal hormone deficiency. A systematic literature search was conducted, and the evidence was graded according to the Grading of Recommendations, Assessment, Development and Evaluation system. If the evidence was insufficient or lacking, then the conclusions were based on expert opinion. The guideline includes recommendations for puberty induction with oestrogen or testosterone. Publications on the induction of puberty with follicle-stimulation hormone and human chorionic gonadotrophin in hypogonadotropic hypogonadism are reviewed. Specific issues in individuals with Klinefelter syndrome or androgen insensitivity syndrome are considered. The expert panel recommends that pubertal induction or sex hormone replacement to sustain puberty should be cared for by a multidisciplinary team. Children with a known condition should be followed from the age of 8 years for girls and 9 years for boys. Puberty induction should be individualised but considered at 11 years in girls and 12 years in boys. Psychological aspects of puberty and fertility issues are especially important to address in individuals with sex development disorders or congenital pituitary deficiencies. The transition of these young adults highlights the importance of a multidisciplinary approach, to discuss both medical issues and social and psychological issues that arise in the context of these chronic conditions.

Screening of Islet Autoantibodies for Children in the General Population: A Position Statement Endorsed by the European Society for Paediatric Endocrinology.

Type 1 diabetes (T1D) is the most frequent chronic autoimmune disease in childhood and adolescence, its incidence is increasing particularly in toddlers and preschool children, and up to 60% of young patients present with diabetic ketoacidosis (DKA), a severe and life-threatening complication. So far, the majority of screening efforts have been performed in the at-risk group, i.e., relatives of people with T1D; anyhow, around 90% of young patients who eventually develop T1D do not have a family history. Some studies in Europe and the USA have clearly shown that a public health screening of children (with positive autoantibodies) is effective in reducing the prevalence of DKA by more than 10 times, decreasing the rate of hospitalization and its costs, providing psychological, emotional, and social support to children and their families. In addition, several treatments and trials are available for children with stage 2 and stage 3 T1D. There is still room for improvement of sensitivity, specificity, positive and negative predictive value in a population screening program; anyhow, there is vivid debate on the opportunity for a screening program in the general population of children at risk for developing T1D. This paper, endorsed by the European Society for Paediatric Endocrinology (ESPE), discusses the issues of a screening program in the general population with the hope that uncertainties and difficulties in this field will be overcome by better screening methods, improved cost-effectiveness, reliable treatments for secondary prevention, and relevant delay in clinically evident T1D in children and adolescents.

60th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE)

60th Annual Meeting of the European Society for Paediatric Endocrinology (ESPE)

An interpretation of "congenital hypothyroidism: a 2020-2021 consensus guidelines update-an ENDO-European Reference Network initiative endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology".

Congenital hypothyroidism is one of the common diseases causing delayed intelligence development and growth retardation in children. In 2021, the ENDO-European Reference Network updated the practice guidelines for the diagnosis and management of congenital hypothyroidism. The guidelines give a comprehensive and detailed description of the screening, diagnosis, and management of congenital hypothyroidism in neonates. This article gives an interpretation of the guidelines in order to provide a reference for clinicians in China.

Congenital hypothyroidism: A 2020-2021 consensus guidelines update-An ENDO-European Reference Network initiative endorsed by the European Society for Pediatric Endocrinology and the European Society for Endocrinology

These updated ENDO-European Reference Network (ENDO-ERN), European Society for Paediatric Endocrinology (ESPE) and European Society for Endocrinology (ESE) guidelines for congenital hypothyroidism will serve as comprehensive review of the literature providing recommendations to all aspects of the disease.

Consensus guidelines of congenital hypothyroidism by the European Society for pediatric endocrinology and the European Society for Endocrinology: key points and comments

Congenital hypothyroidism is an actual clinical problem in pediatric practice. Previous clinical guidelines were published in 2014. The presented clinical recommendations are based on articles published from January 2013 to early 2020. The consensus guidelines include such sections as results of neonatal screening, diagnostics and criteria for treatment, lifelong follow-up, genetics of congenital hypothyroidism, family genetic counselling. The key points of new congenital hypothyroidism guidelines were commented by pediatric endocrinologists of Russians.

Disorders of Sex Development.

Disorders of Sex Development.

Congenital Hypothyroidism: A Review of 2020 European Society for Pediatric Endocrinology and the European Society for Endocrinology Consensus Guidelines

Congenital Hypothyroidism: A Review of 2020 European Society for Pediatric Endocrinology and the European Society for Endocrinology Consensus Guidelines

Greetings From the Editor of Clinical Thyroidology

Clinical ThyroidologyVol. 33, No. 1 Greetings from the EditorFree AccessGreetings From the Editor of Clinical ThyroidologyAngela M. LeungAngela M. LeungSearch for more papers by this authorPublished Online:13 Jan 2021https://doi.org/10.1089/ct.2021;33.4-5AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail DEAR COLLEAGUES,Happy New Year to all, and welcome to our first issue of 2021. As we begin this year, we are delighted to announce some new additions to our editorial board. I believe that healthy turnover and the ability to hear fresh perspectives commenting on the hottest topics in the clinical thyroid literature is critical to the rigor of the journal. Thus, I'm pleased to introduce the following individuals as the newest members of our editorial board, each representing a distinct area of expertise within thyroidology: Drs. Juan P. Brito, Ulla Feldt-Rasmussen, Gary L. Francis, Spyridoula Maraka, Donald S.A. McLeod, Lilah F. Morris-Wiseman, Naykky Singh Ospina, Jesse D. Pasternak, and Erivelto Volpi.This year's first issue begins with paired reviews on the topic of congenital hypothyroidism. Drs. Catherine E. Kerr and Gary L. Francis summarize the recently updated guidelines on congenital hypothyroidism published by the European Society for Pediatric Endocrinology and the European Society for Endocrinology, while Drs. Yanrui Huang and Haixia Guan review findings from the Regional Newborn Screening Laboratory of Lombardy, the only laboratory that has been using differential blood-spot TSH cutoffs for newborn screening of congenital hypothyroidism. Regarding the common condition of primary hypothyroidism, Dr. Daniel Toft summarizes a recent systematic review and meta-analysis showing that more than one third of all users of thyroid hormone therapy remain euthyroid after discontinuing the medication, suggesting substantial overtreatment of hypothyroidism.One of our newest editorial board members, Dr. Erivelto Volpi, discusses the experience of a multicenter Italian cohort studying the efficacy of radio-frequency and laser therapy for the treatment of cytologically benign thyroid nodules. This special piece from the expert perspective of Dr. Volpi is part of a collaborative highlight on ablative techniques for thyroid nodules covered recently across the American Thyroid Association's publications program (Thyroid, Video Endocrinology, and Clinical Thyroidology). In his first review for this journal, Dr. Jesse Pasternak reviews a recent study and shares his personal experience highlighting the promise of translaryngeal ultrasound for assessing the vocal cords prior to thyroid surgery.In the area of thyroid cancer, Dr. Tyler Drake reviews a study exploring the pros and cons of considering a terminology change regarding low-risk papillary thyroid cancers. Drs. Yasuhiro Ito, Naoyoshi Onoda, and Akira Miyauchi review a study examining the serum neutrophil-to-lymphocyte ratio as a promising predictor of tumor activity and worsened prognosis in patients with radioiodine-refractory thyroid cancers. Drs. Gunnar Moen and Martin Biermann examine the use of 18F-FDG–PET/CT versus PET/MR imaging, as demonstrated in a recent study from Italy, in localizing suspected persistent and recurrent differentiated thyroid cancer. Finally, I'm pleased that this issue also includes a case report of a young patient with NUT carcinoma of the thyroid, a rare and aggressive thyroid malignancy due to NUT or NUTM1 gene rearrangements that predominantly arises from head, neck, and thoracic structures.As always, thank you to all our readers who are connecting with us through our social media platforms. I invite everyone to join the conversations regarding the content covered in each month's issue and other related topics:Twitter:https://twitter.com/clinicalthyroid (@clinicalthyroid)Facebook:https://www.facebook.com/ThyroidAssociationLinkedIn:https://www.linkedin.com/company/american-thyroid-associationYoutube:https://www.youtube.com/user/thyroidorgAlso, remember that most of the material covered in Clinical Thyroidology is also translated into shorter lay summaries in our sister journal, Clinical Thyroidology for the Public [CTFP] (https://www.thyroid.org/patient-thyroid-information/ct-for-patients), that is edited by Dr. Alan Farwell and his team each month. The summaries in CTFP may be of use to patients and the public who are interested in reading more about recently published studies in the clinical thyroid literature.I hope that each issue provides helpful reviews, commentaries, editorials, and perspectives regarding how best to treat patients with thyroid disease. Guidelines for submitting Letters to the Editor and select Guest Editorials that cover timely and innovative aspects of clinical thyroid disease management may be found at https://home.liebertpub.com/publications/clinical-thyroidologyand174/623/for-authors.Thank you again for your interest in Clinical Thyroidology. Please feel free to send me any questions or comments at clinicalthyroidology@thyroid.org. We are very much looking forward to another great year of bringing you the top highlights in the clinical thyroid literature.Warmest regards,Angela M. Leung, MD, MScEditor-in-Chief, Clinical ThyroidologyFiguresReferencesRelatedDetails Volume 33Issue 1Jan 2021 InformationCopyright 2021 American Thyroid Association, Inc.To cite this article:Angela M. Leung.Greetings From the Editor of Clinical Thyroidology.Clinical Thyroidology.Jan 2021.4-5.http://doi.org/10.1089/ct.2021;33.4-5Published in Volume: 33 Issue 1: January 13, 2021PDF download

MON-102 Serum Concentrations of FT4 and TSH in the First Six Months of L-Thyroxine Treatment in Infants with Congenital Hypothyroidism: Target Attainment Rates Should Be Improved

Levo-Thyroxine (L-T4) is the medication of choice for treating congenital hypothyroidism (CH). Adequate L-T4 treatment is essential for early neurodevelopment in affected patients. Both under- and overtreatment with L-T4 were associated with long-term adverse neurological outcomes. Based on clinical experience, initial L-T4 dosing does not always result in optimal TSH and FT4 concentrations in all CH patients. The purposes of this study were 1) to quantify FT4 and TSH target attainment rates (TAR) in the first six months of L-T4 treatment in infants with CH, 2) to compare characteristics of patients with FT4 concentrations “OUT of” versus “IN” the target range at first time of monitoring.A multicenter retrospective analysis was conducted in infants born between 1995 and 2018. TSH and FT4 TARs were defined according to the most recent guidelines of the European Society for Paediatric Endocrinology (ESPE), as the percentage of concentrations “in” and “in the upper half” of the corresponding laboratory age-specific reference range for TSH and FT4, respectively.We analyzed a total of 208 TSH and 186 FT4 serum concentrations from 60 patients during the first 6 months of L-T4 treatment. The pretreatment FT4 and TSH serum concentrations (mean±SD) were 8.3±5.7 pmol/L and 338±248 mU/L, respectively. CH severity according to ESPE guidelines was severe, moderate and mild for 32%, 27% and 32% of the patients. Postnatal age (PNA) (mean±SD) at start of treatment was 10±12 days. Starting dose of L-T4 (mean±SD) for severe, moderate and mild CH were 10±4, 10±3, and 7±4 µg/kg/day, respectively. Over the study period, TSH TARs of 63% did not further improve between the first monitoring (mean at 17 days of treatment) and fourth monitoring (mean at 4 months of treatment), while FT4 TARs increased from 22% to 45% paralleled with a decrease of too high FT4 values from 55% to 21%.Comparing patients with FT4 concentrations “OUT of” versus “IN” the target range at first time monitoring (16 versus 18 days after starting treatment; p=0.45), they did not differ in pretreatment FT4 concentrations (p=0.2). In contrast, patients who had FT4 concentrations “OUT of” versus “IN” the target range received first dose of L-T4 at an earlier median PNA (7 versus 16 days; p=0.008), had higher pretreatment mean TSH concentrations (364 versus 181 mU/L; p=0.02) and received a higher mean initial L-T4 dose (10.3 versus 7.1 µg/kg/day; p=0.01).First, our results show that FT4 and TSH target ranges were not reached in all patients in the first six months of treatment. Second, our data suggest that TARs could be improved by individualizing initial L-T4 dosing not only according to pretreatment FT4 but also to pretreatment TSH concentrations. L-T4 dosing optimization is needed in this population.

Observational study of disorders of sex development in Yaounde, Cameroon.

Introduction According to the current classification of the Lawson Wilkins Pediatric Endocrine Society (LWPES) and the European Society for Pediatric Endocrinology (ESPE) of Disorders of Sex Development (DSD), etiologies vary around the world. Ethnic or genetic diversity probably explains this variability. We therefore conducted the present study on etiologies of DSDs in a country from central Africa. Methods We carried out an observational retrospective study at the Pediatric Endocrinology Unit of the Mother and Child Centre of the Chantal Biya Foundation in Yaounde, Cameroon from May 2013 to December 2019. All patients diagnosed with a DSD were included, and incomplete files excluded. Results We included 80 patients diagnosed with DSD during the study period. The 46,XX DSD were the most frequent in our study population (n = 41, 51.25%), with congenital adrenal hyperplasia (CAH) as the main diagnosis. The 46,XY DSD accounted for 33.75% and sex chromosome DSD group represented 15% of the study population. Conclusions DSDs are not an exceptional diagnosis in a Sub-Saharan context. 46,XX DSD are the most prevalent diagnosis in our setting. The diagnosis of all these affections is late compared to other centers, justifying advocacy for neonatal screening of DSDs in our context.

Carlo Acerini - raging against the dying of the light.

Carlo Acerini - raging against the dying of the light.

Dynamic Alterations in Linear Growth and Endocrine Parameters in Children with Obesity Compared to Normal-Weight Children from Infancy to Adolescence

Background: Obesity can affect growth and development of children but there is uncertainty regarding the dynamics and potential causes. We assessed the growth dynamics of children with obesity from infancy to adolescence and evaluated associated endocrine and metabolic changes. Methods: In the population-based LIFE Child and the obesity-enriched Leipzig Obesity Childhood Cohorts encompassing 7,961 children (35,134 measurements), we compared (parental-height-corrected) height, growth velocities and serum hormone levels between normal-weight and children with obesity aged 0 to 20 years. Findings: Children with obesity were significantly taller than normal-weight children, independently of parental height, reaching a maximum difference of 7·6 cm at age 6-7 years. Already at birth, children with obesity were up to 0·5 cm taller and had slightly increased growth velocities of up to 0·9 cm/y (+1·1 SDS) in early childhood. During puberty, children with obesity showed a catch-down in height, with an almost blunted growth spurt particularly in boys. The reduction in pubertal growth velocity by 30% coincided with a decrease in levels of insulin-like growth factor-1 (IGF-1) (by 17%) and testosterone (by 61%) in boys, as well as with reductions in estradiol (by 44%) in girls with obesity. Interpretation: Children with obesity are taller in early childhood with catch-down growth in puberty. The blunted pubertal growth spurt is paralleled by reduced serum levels of IGF-1 and sex hormones. Funding: German Research Foundation, European Union, European Regional Development Fund, Free State of Saxony, German Federal Ministry of Education and Research, and European Society for Pediatric Endocrinology. Declaration of Interest: The authors have nothing to declare. Ethical Approval: The study was approved by the ethics committee of the University of Leipzig (NCT02550236, NCT02208141, NCT01605123).

Trajectories of changes in glucose tolerance in a multiethnic cohort of obese youths: an observational prospective analysis

Type 2 diabetes is preceded by a prediabetic stage of impaired glucose tolerance that affects 10-23% of youth and is expected to double over the next decade. The natural history of impaired glucose tolerance and the determinants of β-cell dynamic response have never been investigated longitudinally in young people. We aimed to investigate the clinical and metabolic determinants of longitudinal glucose tolerance changes and β-cell function in a multiethnic cohort of obese youth. We followed up prospectively a multiethnic cohort of overweight and obese (body-mass index >85th percentile) adolescents with baseline normal glucose tolerance (plasma glucose <140 mg/dL) or impaired glucose tolerance (plasma glucose 140-199 mg/dL) at the Yale Pediatric Obesity Clinic (CT, USA). All participants underwent a 3-h oral glucose tolerance test at baseline and after 2 years to estimate insulin secretion (oral disposition index) in the context of body insulin sensitivity. As part of standard care at the clinic, all participants received dietary advice and underwent dietary assessment every 5-6 months. No structured lifestyle or pharmacological intervention was administered. Between January, 2010, and December, 2016, 526 adolescents (mean age 12·7 years, range 10·6-14·2) were enrolled to our study. At baseline, 364 had normal and 162 had impaired glucose tolerance. Median follow-up was 2·9 years (IQR 2·7-3·1). 105 (65%) of 162 with impaired glucose tolerance at baseline reverted to normal glucose tolerance at follow-up, 44 (27%) had persistent impaired glucose tolerance, and 13 (8%) progressed to type 2 diabetes. A feature of reversion to normal glucose tolerance was a roughly four-fold increase in the oral disposition index (from median 0·94 [IQR 0·68-1·35] at baseline to 3·90 [2·58-6·08] at follow-up; p<0·0001) and a significantly higher oral disposition index at follow-up compared with participants who maintained normal glucose tolerance across the study period (median 3·90 [IQR 2·58-6·08] vs 1·59 [1·12-2·23]; p<0·0001). By contrast, a decrease in insulin secretion was seen in participants who had persistent impaired glucose tolerance (median 1·31 [IQR 1·01-1·85]; p<0·0001) or who progressed to type 2 diabetes (0·20 [0·12-0·58]; p<0·0001), compared with participants who maintained normal glucose tolerance across the study period. Non-Hispanic white ethnic origin conferred five times the odds of reversion to normal glucose tolerance compared with non-Hispanic black ethnic origin (OR 5·06, 95% CI 1·86-13·76; p=0·001), with a two times greater annual increase in the oral disposition index (β 2·32, 95% CI 0·05-4·60; p=0·045). Impaired glucose tolerance is highly reversible in obese adolescents. Ethnic origin is the main clinical modifier of the dynamic β-cell response to prediabetic hyperglycaemia and, thus, determines the reversibility of impaired glucose tolerance, or its persistence. Therapeutic interventions for impaired glucose tolerance should target the specific mechanisms underpinning glucose tolerance changes in high-risk ethnic groups. National Institutes of Health (National Institute of Child Health and Human Development, National Center for Research Resources, and National Institute of Diabetes and Digestive and Kidney Diseases), American Diabetes Association, International Society for Pediatric and Adolescent Diabetes, Robert Leet Patterson and Clara Guthrie Patterson Trust, European Society for Pediatric Endocrinology, American Heart Association, and the Allen Foundation.

Type 1 Diabetes in Children and Adolescents.

Type 1 Diabetes in Children and Adolescents.