Diabetes care practices and outcomes in 40.000 children and adolescents with type 1 diabetes from the SWEET registry during the COVID-19 pandemic.

AIMS: This study aimed to provide a global insight into initiatives in type 1 diabetes care driven by the COVID-19 pandemic and associations with glycemic outcomes. METHODS: An online questionnaire regarding diabetes care before and during the pandemic was sent to all centers (n = 97, 66,985 youth with type 1 diabetes) active in the SWEET registry. Eighty-two responded, and 70 (42,798 youth with type 1 diabetes) had available data (from individuals with type 1 diabetes duration >3 months, aged ≤21 years) for all 4 years from 2018 to 2021. Statistical models were adjusted, among others, for technology use. RESULTS: Sixty-five centers provided telemedicine during COVID-19. Among those centers naive to telemedicine before the pandemic (n = 22), four continued only face-to-face visits. Centers that transitioned partially to telemedicine (n = 32) showed a steady increase in HbA1c between 2018 and 2021 (p < 0.001). Those that transitioned mainly to telemedicine (n = 33 %) improved HbA1c in 2021 compared to 2018 (p < 0.001). CONCLUSIONS: Changes to models of care delivery driven by the pandemic showed significant associations with HbA1c shortly after the pandemic outbreak and 2 years of follow-up. The association appeared independent of the concomitant increase in technology use among youth with type 1 diabetes.

Glycemic Outcome Associated With Insulin Pump and Glucose Sensor Use in Children and Adolescents With Type 1 Diabetes. Data From the International Pediatric Registry SWEET.

OBJECTIVE: Insulin delivery methods, glucose-monitoring modalities, and related outcomes were examined in a large, international, diverse cohort of children and adolescents with type 1 diabetes from the Better Control in Pediatric and Adolescent Diabetes: Working to Create Centers of Reference (SWEET) -Registry. RESEARCH DESIGN AND METHODS: Participants with type 1 diabetes of ≥1 year, aged ≤18 years, and who had documented pump or sensor usage during the period August 2017-July 2019 were stratified into four categories: injections-no sensor (referent); injections + sensor; pump-no sensor; and pump + sensor. HbA1c and proportion of patients with diabetic ketoacidosis (DKA) or severe hypoglycemia (SH) were analyzed; linear and logistic regression models adjusted for demographics, region, and gross domestic product per capita were applied. RESULTS: Data of 25,654 participants were analyzed. The proportions of participants (adjusted HbA1c data) by study group were as follows: injections-no sensor group, 37.44% (8.72; 95% CI 8.68-8.75); injections + sensor group, 14.98% (8.30; 95% CI 8.25-8.35); pump-no sensor group, 17.22% (8.07; 95% CI 8.03-8.12); and pump + sensor group, 30.35% (7.81; 95% CI 7.77-7.84). HbA1c was lower in all categories of participants who used a pump and/or sensor compared with the injections-no sensor treatment method (P < 0.001). The proportion of DKA episodes was lower in participants in the pump + sensor (1.98%; 95% CI 1.64-2.48; P < 0.001) and the pump-no sensor (2.02%; 95% CI 1.64-2.48; P < 0.05) groups when compared with those in the injections-no sensor group (2.91%; 95% CI 2.59-3.31). The proportion of participants experiencing SH was lower in pump-no sensor group (1.10%; 95% CI 0.85-1.43; P < 0.001) but higher in the injections + sensor group (4.25%; 95% CI 3.65-4.95; P < 0.001) compared with the injections-no sensor group (2.35%; 95% CI 2.04-2.71). CONCLUSIONS: Lower HbA1c and fewer DKA episodes were observed in participants using either a pump or continuous glucose monitoring (CGM) or both. Pump use was associated with a lower rate of SH. Across SWEET centers, use of pumps and CGM is increasing. The concomitant use of pump and CGM was associated with an additive benefit.

Determinants of insulin resistance in children exposed to gestational diabetes in utero.

BACKGROUND: The evolution of increased adiposity and cardiometabolic risk in offspring exposed to maternal gestational diabetes (GDM) is not well understood. OBJECTIVE: (a) To evaluate the impact of in utero exposure to GDM and maternal weight status on homeostasis model assessment of insulin resistance (HOMA-IR) in the offspring longitudinally from 1 to 3 years of age and (b) to compare body mass index (BMI) and HOMA-IR in GDM and non-GDM exposed offspring at 1 and 3 years of age. METHODS: A prospective cohort of children born to mothers with and without GDM underwent metabolic characterization between birth and 3 years of age. RESULTS: In the overall cohort, weight gain between birth and 3 years of age was positively associated with HOMA-IR (ß = 0.1491, P = .02), independent of maternal weight status. HOMA-IR was not different between GDM and non-GDM exposed children from 1 to 3 years of age; however, BMI z score was greater in GDM exposed children at 3 years of age. Among non-GDM exposed children, male sex predicted a 35.1% lower HOMA-IR (P = .03). In GDM exposed offspring, a 1 unit increase in maternal insulin sensitivity predicted a 20.8% decrease in HOMA-IR (P = .002). CONCLUSIONS: Overall, weight gain in the first 3 years of life was positively associated with HOMA-IR, while insulin sensitivity of mothers with GDM negatively predicted HOMA-IR in the offspring. Our findings indicate the need to target weight trajectories in early life, as well as maternal factors during gestation to improve metabolic outcomes in the offspring, particularly those exposed to GDM.

Evaluation of anthropometric measures for assessment of cardiometabolic risk in early childhood.

OBJECTIVE: Waist-to-height ratio has been shown to be an important indicator of cardiometabolic risk. There are few studies evaluating this measure against existing measures of adiposity and cardiometabolic markers in early childhood. The objectives were: (i) to determine in young children the ability of waist-to-height ratio, BMI z-score, weight for length, and sum of skin fold thickness to predict cardiometabolic risk and (ii) to examine this association at ages 1, 3 and 5 years. DESIGN: Prospective cohort study. SETTING: A university hospital in Toronto, Ontario. PARTICIPANTS: Infants at 1 (n 406), 3 (n 112) and 5 years of age (n 94) born to mothers with and without gestational diabetes mellitus. RESULTS: Weight for length and BMI z-score demonstrated the strongest correlations with biochemical measures compared to waist-to-height ratio, including leptin (at 5 years, weight for length z-score: ρ = 0·65, P < 0·001; BMI z-score: ρ = 0·67, P < 0·001) and measures of insulin resistance (at 3 years, weight for length z-score: ρ = 0·25, P = 0·02; BMI z-score: ρ = 0·24, P = 0·02). The magnitude of associations between anthropometric measures and biochemical measures strengthened over time. Weight for length and BMI z-scores were moderately correlated with overall measures of fat mass as measured by dual-energy X-ray absorptiometry (ρ = 0·65, P = 0·00; ρ = 0·61, P = 0·01). CONCLUSIONS: Waist-to-height ratio was not superior to existing measures in predicting cardiometabolic risk in young children. BMI z-score is a preferred measure of adiposity between birth and 5 years of age.

Breaking barriers: Adjunctive use of the Ontario Telemedicine Network (OTN) to reach adolescents with obesity living in remote locations.

INTRODUCTION: Implementation of telemedicine has been shown to improve health outcomes, such as body mass index (BMI). However, it is unclear whether telemedicine is useful alongside traditional weight-management programmes for adolescents with complex obesity. The objective was to evaluate implementation of the Ontario Telemedicine Network (OTN), a videoconferencing programme, as an adjunctive tool to face-to-face counselling within the setting of an established interdisciplinary obesity treatment programme. METHODS: Our observational cohort included two groups of adolescents enrolled in a clinical obesity-management programme over a two year period. Adolescents (n = 50) in group 1 attended both in-person and virtual visits (OTN group), and adolescents (n = 50) in group 2 received only in-person visits (comparison group). Within the OTN group, satisfaction survey responses were compared between patients and healthcare professionals. Change in BMI per month, paediatric quality of life scores, session attendance and demographic variables were compared between groups. RESULTS: OTN subjects averaged 4.9 telehealth visits per adolescent over the two year programme. Both OTN and comparison groups had similar changes in BMI (p = 0.757), with increases over time (p = 0.042). Paediatric quality of life scores in both groups improved over time compared to baseline (p < 0.001), with higher scores for children compared to parental-reported child scores (p = 0.008). Both adolescents and healthcare professionals using the OTN were similarly satisfied with their experience. CONCLUSION: Adjunctive use of the OTN within the setting of a weight-management programme is feasible, well accepted by families and healthcare providers, and led to similar outcomes compared to usual care.

Severe Neonatal Cholestasis as an Early Presentation of McCune-Albright Syndrome

McCune-Albright syndrome (MAS) is a rare genetic disorder characterized by café-au-lait macules, polyostotic fibrous dysplasia and multiple endocrinopathies. Liver involvement, although described, is a rare complication. We review the case of a child with MAS whose initial presentation was characterized by severe neonatal cholestasis. The case demonstrates a severe phenotype of persistent cholestasis in MAS requiring liver transplantation. This phenotype has been previously considered to be a more benign feature. This case highlights the importance of consideration of MAS as an uncommon but important cause of neonatal cholestasis. Early diagnosis may allow for prompt recognition and treatment of other endocrinopathies.

Emerging treatments for severe obesity in children and adolescents.

Severe obesity in childhood is increasing in prevalence and is associated with considerable morbidity. Studies into pediatric obesity have focused largely on interventions that do not necessarily target the unique biologic or psychological underpinnings for the weight gain in the individual child or adolescent. Outcomes show modest improvement and are of questionable benefit for patients with severe obesity. Although weight is a commonly used outcome, other psychological and metabolic parameters including normalization of physical activity and eating behaviors should be primary outcome goals. The durability of weight loss is often limited by physiologic systems that are evolutionarily designed to promote weight gain. Drug therapies for children are limited, as is their effect on weight and metabolism. Existing drugs that are incidentally found to cause weight loss through off-target effects are being actively investigated for obesity indications. Bariatric surgery results in the most significant weight reduction, but it is associated with potential morbidity and long term data are not available for adolescents undergoing this procedure. As understanding of the biologic and psychosocial contributors to eating behaviors and body weight regulation increases, multifaceted and targeted behavioral, pharmacological, and surgical treatment algorithms should be developed and applied to target the underlying pathways involved for the individual child or adolescent with severe obesity.

Spondyloocular Syndrome: Novel Mutations in XYLT2 Gene and Expansion of the Phenotypic Spectrum.

Spondyloocular syndrome is an autosomal-recessive disorder with spinal compression fractures, osteoporosis, and cataract. Mutations in XYLT2, encoding isoform of xylosyltransferase, were recently identified as the cause of the syndrome. We report on 4 patients, 2 unrelated patients and 2 siblings, with spondyloocular syndrome and novel mutations in XYLT2. Exome sequencing revealed a homozygous nonsense mutation, NM_022167.3(XYLT2): c.2188C>T, resulting in a premature stop codon (p.Arg730*) in a female patient. The patient presents visual impairment, generalized osteoporosis, short stature with short trunk, spinal compression fractures, and increased intervertebral disc space and hearing loss. We extended our XYLT2 analysis to a cohort of 22 patients with generalized osteoporosis, mostly from consanguineous families. In this cohort, we found by Sanger sequencing 2 siblings and 1 single patient who were homozygous for missense mutations in the XYLT2 gene (p.Arg563Gly and p.Leu605Pro). The patients had osteoporosis, compression fractures, cataracts, and hearing loss. Bisphosphonate treatment in 1 patient resulted in almost complete normalization of vertebral structures by adolescence, whereas treatment response in the others was variable. This report together with a previous study shows that mutations in the XYLT2 gene result in a variable phenotype dominated by spinal osteoporosis, cataract, and hearing loss. © 2016 American Society for Bone and Mineral Research.

Utility of the Oral Glucose Tolerance Test to Assess Glucose Abnormalities in Adolescents with Polycystic Ovary Syndrome.

STUDY OBJECTIVE: The aim of this study was to examine the prevalence of and risk factors for abnormal glucose metabolism in a large population of adolescents with polycystic ovary syndrome (PCOS). DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A retrospective chart review was performed of 360 patients who presented to the pediatric gynecology outpatient clinic for evaluation of PCOS between January 2004 and May 2012. RESULTS: A total of 163 patients fulfilled criteria for a diagnosis of PCOS and had adequate clinical and laboratory data. Twenty-six adolescents (16.0%) had impaired glucose tolerance and 2 patients (1.2%) met criteria for a provisional diagnosis of type 2 diabetes. All 28 subjects with abnormal glucose metabolism were identified using the 2-hour plasma glucose of the oral glucose tolerance test. Conversely, the fasting glucose values only successfully detected 2 patients with hyperglycemia, both of whom also had abnormal 2-hour glucose levels. Adolescents with abnormal glucose metabolism were more likely to have reported a positive family history (P = .02) and had higher body mass index z scores (2.8 ± 1.1 vs 1.8 ± 1.2; P < .01). When patients were classified into normal weight (n = 29) and obese/overweight groups (n = 117), all of the patients with abnormal glucose metabolism were overweight or obese. CONCLUSION: In the largest series to date, we describe a prevalence of abnormal glucose metabolism in adolescent patients with PCOS of 17.2%. Abnormal glucose metabolism is associated with many of the known risk factors for metabolic syndrome. Our results support that the oral glucose tolerance test is a superior diagnostic test to assess abnormal glucose levels in overweight and obese adolescents but that this test might have limited utility in normal weight adolescents with PCOS.