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In vivo corneal confocal microscopy (CCM) is a novel, rapid, and non-invasive technique that identifies early small fiber damage and can predict the progression and development of clinical neuropathy in adults with type 1 diabetes. However, its usefulness in children is not well established. This study compared corneal confocal microscopy with neuropathic symptoms, signs, and objective measures of neuropathy for the diagnosis of diabetic neuropathy in children with type 1 diabetes.A total of 83 children with type 1 diabetes and 83 healthy participants of similar age underwent assessment of neuropathy symptoms, signs, nerve conduction studies, quantitative sensory and autonomic function testing, and in vivo CCM.Only of 3/83 (4%) children with type 1 diabetes had subclinical neuropathy. However, corneal nerve fiber density (p = 0.001), branch density (p = 0.006), fiber length (p = 0.002), tibial motor nerve amplitude and conduction velocity, and sural sensory nerve amplitude and conduction velocity (all p 0.004) were lower in participants with type 1 diabetes than in the controls. Vibration, cooling, and warm perception thresholds and deep breathing heart rate variability were not found to be different (all p 0.05) between children with type 1 diabetes and healthy controls. Multivariate regression analysis identified a possible association between body mass index and decreased corneal nerves.Decreased corneal nerves and abnormal nerve conduction were found in children with type 1 diabetes. CCM may allow rapid objective detection of subclinical diabetic neuropathy in children and adolescents with type 1 diabetes.

Introduction The lack of attention to transgender and gender diverse (TGD) people in undergraduate medical education (UME) is a point of concern, particularly among medical students. A project was undertaken to develop a UME curriculum framework for teaching the healthcare needs of TGD people. Methods Using a modified Delphi methodology, four rounds of surveys were presented to an expert stakeholder group that included content experts, generalist physicians, UME teaching faculty, and medical students. Questions covered what content should be taught, who should teach the content, and how much time should be dedicated for this teaching. Once the Delphi process was complete, feedback on the provisional framework was sought from members of the TGD community to ensure it represented their needs and perspectives. Results 71 panel members and 56 community members participated in the study. Core values included the scope of the framework, and topics such as inclusivity, and safety in practice and in teaching. The framework included terminology, epidemiology, medical and surgical treatment, mental health, sexual and reproductive health, and routine primary care. There was also guidance on who should teach, time to be allocated, and the learning environment. Discussion There is a clear need to train tomorrow’s doctors to provide competent and respectful healthcare services to and for TGD patients. Although local factors will likely shape the way in which this framework will be implemented in different contexts, this paper outlines a core UME-level curriculum framework for Canada and, potentially, for use in other parts of the world. Supplementary Information The online version of this article (10.1007/s40037-021-00692-7) contains supplementary material, which is available to authorized users.

Objective: The beta-cell stress hypothesis suggests that increased insulin demand contributes to the development of type 1 diabetes. In the TRIGR trial we set out to assess the profile of plasma glucose and HbA1c before the diagnosis of clinical diabetes compared to nondiabetic children. Research Design and Methods: A cohort of children (N = 2159) with an affected first-degree relative and increased HLA risk were recruited 2002-2007 and followed until 2017. To study the relationship between plasma glucose/HbA1c and the development of autoantibodies or clinical disease Kaplan-Meir curves were developed. Mixed models were constructed for plasma glucose and HbA1c separately. Results: A family history of type 2 diabetes was related to an increase in plasma glucose (p < 0.001). An increase in glucose from the previous sample predicted clinical diabetes (p < 0.001) but not autoantibodies. An increase of HbA1c of 20% or 30% from the previous sample predicted the development of any autoantibody (p < 0.003 resp < 0.001) and the development of diabetes (p < 0.002 resp < 0.001. Participants without autoantibodies had lower HbA1c (mean 5.18%, STD 0.24; mean 33.08 mmol/mol, STD 2.85) than those who progressed to clinical disease (5.31%, 0.42; 34.46 mmol/mol, 4.68; p < 0.001) but higher than those who developed any autoantibody (5.10%, 0.30; 32.21 mmol/mol, 3.49; p < 0.001), or multiple autoantibodies (5.11%, 0.35; 32.26 mmol/mol, 3.92; p < 0.003). Conclusions: A pronounced increase in plasma glucose and HbA1c precedes development of clinical diabetes, while the association between plasma glucose or HbA1c and development of autoantibodies is complex. Increased insulin demand may contribute to development of type 1 diabetes. Funding Agencies|Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [HD040364, HD042444, HD051997]; Special Statutory Funding Program for Type 1 Diabetes Research; Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR); Juvenile Diabetes Research Foundation InternationalJuvenile Diabetes Research Foundation; Academy of FinlandAcademy of FinlandEuropean Commission; Commission of the European CommunitiesEuropean Commission [QLK1-2002-00372]; EFSD/JDRF/Novo Nordisk Focused Research Grant

To evaluate the incremental impact of resistance training on HbA1c, fitness, body composition and cardiometabolic risk factors in aerobically-active people with type 1 diabetes.The Resistance Exercise in Already-active Diabetic Individuals (READI) trial (NCT00410436) was a four-centre randomized parallel-group trial. After a 5-week run-in period with diabetes management optimization, 131 aerobically-active individuals with type 1 diabetes were randomized to resistance exercise (n = 71, intervention - INT) or control (n = 60, CON) for 22 additional weeks. Both groups maintained their aerobic activities and were provided dietary counselling throughout. Exercise training was three times per week at community-based facilities. The primary outcome was HbA1c, and secondary outcomes included fitness (peak oxygen consumption, muscle strength), body composition (anthropometrics, dual-energy X-ray absorptiometry, computed tomography) and cardiometabolic risk markers (lipids, apolipoproteins). Assessors were blinded to group allocation.There were no significant differences in HbA1c change between INT and CON. Declines in HbA1c [INT: 7.75 ± 0.10% (61.2 ± 1.1 mmol/mol) to 7.55 ± 0.10% (59 ± 1.1 mmol/mol); CON: 7.70 ± 0.11% (60.7 ± 1.2 mmol/mol) to 7.57 ± 0.11% (59.6 ± 1.3 mmol/mol); intergroup difference in change -0.07 [95% CI -0.31, 0.18]. Waist circumference decreased more in INT than CON after six months (p = 0.02). Muscular strength increased more in INT than in CON (p 0.001). There were no intergroup differences in hypoglycemia or any other variables.Adding resistance training did not impact glycemia, but it increased strength and reduced waist circumference, in aerobically active individuals with type 1 diabetes.

Objective The COVID‐19 pandemic has led to significant public health measures that have resulted in decreased acute pediatric care utilization. We evaluated whether the rate of severe presentations of new onset type 1 diabetes (DM1), such as, diabetic ketoacidosis (DKA) has changed since the COVID‐19 public health measures were enacted. Research Design and Methods A retrospective chart review of children less than 18 years of age presenting with new onset DM1 during the pandemic period of March 17, 2020 to August 31, 2020 was conducted at two tertiary care pediatric hospitals in Alberta, Canada. Rates of DKA and severe DKA were compared to the same time period in the year 2019 (pre‐pandemic control). Results The number of children presenting with newly diagnosed DM1 was similar during the pandemic year of 2020 compared with 2019 (107 children in 2020 vs. 114 in 2019). The frequency of DKA at DM1 onset was significantly higher in the pandemic period (68.2% vs 45.6%; p

Youth with type 1 diabetes are at high risk for loss to follow-up during the transition from paediatric to adult diabetes care. Our aim was to assess the effect of a communication technology enhanced transition coordinator intervention compared with usual care on clinic attendance among transitioning youth with type 1 diabetes. In this open label, pragmatic clinical trial of youth with type 1 diabetes, aged 17–18 years, transitioning from paediatric to adult diabetes care, the intervention group received support from a transition coordinator who used communication technology and the control group received usual care. The primary outcome was the proportion of individuals that did not attend at least one routine clinic visit in adult diabetes care within 1 year after transfer. Secondary outcomes included diabetes-related clinical outcomes and quality of life measures. There were no baseline differences in age, sex, HbA1c and number of follow-up visits, emergency department visits and diabetic ketoacidosis admissions in the 1 year prior to transition between the usual care (n = 101) and intervention (n = 102) groups. In the year following transfer, 47.1% in the usual care group vs 11.9% in the intervention group did not attend any outpatient diabetes appointments (p

Objective Despite the significant morbidity and mortality associated with pheochromocytoma and paraganglioma, little is known about their epidemiology. The primary objective was to determine the incidence of pheochromocytoma and paraganglioma in an ethnically diverse population. A secondary objective was to develop and validate algorithms for case detection using laboratory and administrative data. Design Population-based cohort study in Alberta, Canada from 2012 to 2019. Methods Patients with pheochromocytoma or paraganglioma were identified using linked administrative databases and clinical records. Annual incidence rates per 100 000 people were calculated and stratified according to age and sex. Algorithms to identify pheochromocytoma and paraganglioma, based on laboratory and administrative data, were evaluated. Results A total of 239 patients with pheochromocytoma or paraganglioma (collectively with 251 tumors) were identified from a population of 5 196 368 people over a period of 7 years. The overall incidence of pheochromocytoma or paraganglioma was 0.66 cases per 100 000 people per year. The frequency of pheochromocytoma and paraganglioma increased with age and was highest in individuals aged 60–79 years (8.85 and 14.68 cases per 100 000 people per year for males and females, respectively). An algorithm based on laboratory data (metanephrine >two-fold or normetanephrine >three-fold higher than the upper limit of normal) closely approximated the true frequency of pheochromocytoma and paraganglioma with an estimated incidence of 0.54 cases per 100 000 people per year. Conslusion The incidence of pheochromocytoma and paraganglioma in an unselected population of western Canada was unexpectedly higher than rates reported from other areas of the world.

Objectives: Biallelic pathogenic variants in CYPA24A1 and SLC34A1 are causes of idiopathic infantile hypercalcemia. Pathogenic variants in both may also give rise to hypercalciuria with nephrocalcinosis or nephrolithiasis without previous hypercalcemia (renal group). Our objective was to examine the frequency of CYP24A1 or SLC34A1 variants in children with early hypercalcemia or late-onset hypercalciuria. Method: Forty-one children from 7 centers across Canada were recruited. Local investigations were undertaken. The serum was evaluated by liquid chromatography tandem-mass spectrometry for the ratio of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3, (25-OH-D3:24,25-(OH)2D3), an elevation pathognomonic for the loss of function of the CYP24A1 enzyme. Mutational analyses were undertaken. Family cascade screening was performed if pathogenic variants were detected in probands. Results: Twenty-nine children had early-onset hypercalcemia; none had elevated 25-OH-D3:24,25-(OH)2D3 or variants. Interestingly, 2 of 12 in the renal group had elevated 25-OH-D3:24,25-(OH)2D3 and presented as preadolescents. In case 1, cascade testing revealed a sibling and parent with asymptomatic pathogenic variants in CYP24A1. Four CYP24A1 pathogenic variants were identified in these 2 probands: 3 have been described in European populations, and 1 is a rare variant in exon 7 (c931delC) that is likely pathogenic. No SLC34A1 pathogenic variants were detected. Conclusion: In Canada, pathogenic variants in CYP24A1 appear to manifest with late-onset hypercalciuria and its sequelae. The 25-OH-D3:24,25-(OH)2D3 ratio is an excellent tool for screening for biallelic pathogenic variants in CYP24A1. We confirm that cascade testing is important for these variants.

Aims/hypothesis The aim of this work was to examine the relationship between family history of type 1 diabetes, birthweight, growth during the first 2 years and development of multiple beta cell autoantibodies in children with a first-degree relative with type 1 diabetes and HLA-conferred disease susceptibility. Methods In a secondary analysis of the Trial to Reduce IDDM in the Genetically at Risk (TRIGR), clinical characteristics and development of beta cell autoantibodies were compared in relation to family history of type 1 diabetes (mother vs father vs sibling) in 2074 children from families with a single affected family member. Results Multiple autoantibodies (>= 2 of 5 measured) developed in 277 (13%) children: 107 (10%), 114 (16%) and 56 (18%) born with a mother, father or sibling with type 1 diabetes, respectively (p < 0.001). The HR for time to multiple autoimmunity was 0.54 (95% CI 0.39, 0.75) in offspring of affected mothers (n = 107/1046,p < 0.001) and 0.81 (95% CI 0.59, 1.11) (n = 114/722,p = 0.19) in offspring of affected fathers, compared with participants with a sibling with type 1 diabetes (comparator groupn = 56/306). The time to the first autoantibody present (to insulin, GAD, tyrosine phosphatase-related insulinoma-associated 2 molecules, islet cell or zinc transporter 8) was similar in the three groups. Height velocity (zscore/year) in the first 24 months was independently associated with developing multiple antibodies in the total cohort (HR 1.31 [95% CI 1.01, 1.70],p = 0.04). A higher birthweight in children born to an affected mother vs affected father or an affected sibling was not related to the risk of multiple autoimmunity. Conclusions/interpretation The risk of developing multiple autoantibodies was lower in children with maternal type 1 diabetes. For the whole group, this risk of developing multiple autoantibodies was independent of birthweight but was greater in those with increased height velocity during the first 2 years of life. However, the risk associated with paternal type 1 diabetes was not linked to differences in birthweight or early growth. Funding Agencies|University of Helsinki; Helsinki University Central Hospital; Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD) [HD040364, HD042444, HD051997]; Special Statutory Funding Program for Type 1 diabetes Research; Canadian Institutes of Health ResearchCanadian Institutes of Health Research (CIHR); JDRF InternationalJuvenile Diabetes Research Foundation; Finnish Academy of SciencesAcademy of Finland; Commission of the European Communities (specific RTD programme `Quality of Life and management of Living Resources) [QLK1-2002-00372]; EFSD/JDRF/Novo Nordisk Focused Research Grant

Objective We previously highlighted the problem of frequent false positives in 24 hour urine normetanephrine(UNM) measurements owing to reference intervals that are inappropriately low for the population being screened for pheochromocytoma. Using a large population database, we devised new age-stratified reference intervals for the 24 hour UNM test that were higher compared to previous. However, it was uncertain as to whether this would compromise test sensitivity for true pheochromocytoma cases. Design and Methods: Retrospective analysis of all pheochromocytoma cases from a recently constructed provincial registry. All confirmed cases had their diagnostic UNM results retrospectively re-analysed according to the newly proposed UNM reference intervals to determine the percentage and phenotype of cases that might have been theoretically missed with the new reference range. Results After excluding pediatric and non-secretory head and neck paragangliomas, there were 60 confirmed pheochromocytoma cases. Using prior reference intervals, 51/60 (85%) had an abnormally high UNM. Of the 9 with normal UNM, 4 had a high urine metanephrine(UMN), 5 had normal levels of both UNM and UMN such that 55/60 had abnormal test results, representing the historical combined test sensitivity of 92%. Using the proposed reference interval, 43/60 (72%) had high UNM results. Of the 17 with normal UNM, 12 had high UMN, 5 had normal levels of both UNM and UMN. Therefore, 55/60 patients had had elevations in either UNM or UMN, corresponding to an identical combined test sensitivity of 92%. Conclusions Reference intervals for UNM derived from actual clinical population screening data are higher than in traditional healthy volunteers. Use of these more appropriate reference intervals can significantly reduce the false positive rate without compromising test sensitivity for true pheochromocytoma.

BACKGROUND AND OBJECTIVES Referrals of transgender and gender-diverse (trans) youth to medical clinics for gender-affirming care have increased. We described characteristics of trans youth in Canada at first referral visit. METHODS Baseline clinical and survey data (2017–2019) were collected for Trans Youth CAN!, a 10-clinic prospective cohort of n = 174 pubertal and postpubertal youth RESULTS Of youth, 137 were transmasculine (assigned female) and 37 transfeminine (assigned male); 69.0% were aged 14 to 15, 18.8% Indigenous, 6.6% visible minorities, 25.7% from immigrant families, and 27.1% low income. Most (66.0%) were gender-aware before age 12. Only 58.1% of transfeminine youth lived in their gender full-time versus 90.1% of transmasculine (P < .001). Although transmasculine youth were more likely than transfeminine youth to report depressive symptoms (21.2% vs 10.8%; P = .03) and anxiety (66.1% vs 33.3%; P < .001), suicidality was similarly high overall (past-year ideation: 34.5%, attempts: 16.8%). All were in school; 62.0% reported strong parental gender support, with parents the most common support persons (91.9%). Two-thirds of families reported external gender-related stressors. Youth had met with a range of providers (68.5% with a family physician). At clinic visit, 62.4% were prescribed hormonal suppression or hormone therapy, most commonly depot leuprolide acetate. CONCLUSIONS Trans youth in Canada attending clinics for hormonal suppression or gender-affirming hormones were generally healthy but with depression, anxiety, and support needs.

Aims: To evaluate access to screening tools for monogenic diabetes in paediatric diabetes centres across the world and its impact on diagnosis and clinical outcomes of children and youth with genetic forms of diabetes. Methods: 79 centres from the SWEET diabetes registry including 53,207 children with diabetes participated in a survey on accessibility and use of diabetes related antibodies, c-peptide and genetic testing. Results: 73, 63 and 62 participating centres had access to c-peptide, antibody and genetic testing, respectively. Access to antibody testing was associated with higher proportion of patients with rare forms of diabetes identified with monogenic diabetes (54 % versus 17 %, p = 0.01), lower average whole clinic HbA1c (7.7[Q1,Q2: 7.3-8.0]%/61[56-64]mmol/mol versus 9.2[8.6-10.0]%/77[70-86]mmol/mol, p < 0.001) and younger age at onset (8.3 [7.3-8.8] versus 9.7 [8.6-12.7] years p < 0.001). Additional access to c-peptide or genetic testing was not related to differences in age at onset or HbA1c outcome. Conclusions: Clinical suspicion and antibody testing are related to identification of different types of diabetes. Implementing access to comprehensive antibody screening may provide important information for selecting individuals for further genetic evaluation. In addition, worse overall clinical outcomes in centers with limited diagnostic capabilities indicate they may also need support for individualized diabetes management. info:eu-repo/semantics/publishedVersion

OBJECTIVE Corneal nerve fiber length (CNFL) has been shown in research studies to identify diabetic peripheral neuropathy (DPN). In this longitudinal diagnostic study, we assessed the ability of CNFL to predict the development of DPN. RESEARCH DESIGN AND METHODS From a multinational cohort of 998 participants with type 1 and type 2 diabetes, we studied the subset of 261 participants who were free of DPN at baseline and completed at least 4 years of follow-up for incident DPN. The predictive validity of CNFL for the development of DPN was determined using time-dependent receiver operating characteristic (ROC) curves. RESULTS A total of 203 participants had type 1 and 58 had type 2 diabetes. Mean follow-up time was 5.8 years (interquartile range 4.2–7.0). New-onset DPN occurred in 60 participants (23%; 4.29 events per 100 person-years). Participants who developed DPN were older and had a higher prevalence of type 2 diabetes, higher BMI, and longer duration of diabetes. The baseline electrophysiology and corneal confocal microscopy parameters were in the normal range but were all significantly lower in participants who developed DPN. The time-dependent area under the ROC curve for CNFL ranged between 0.61 and 0.69 for years 1–5 and was 0.80 at year 6. The optimal diagnostic threshold for a baseline CNFL of 14.1 mm/mm2 was associated with 67% sensitivity, 71% specificity, and a hazard ratio of 2.95 (95% CI 1.70–5.11; P < 0.001) for new-onset DPN. CONCLUSIONS CNFL showed good predictive validity for identifying patients at higher risk of developing DPN ∼6 years in the future.

Type 1 diabetes is a common chronic illness in childhood. Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes. Early recognition of symptoms of diabetes and immediate initiation of treatment are important factors in preventing DKA at first presentation. We describe the numbers of children presenting with DKA at initial diagnosis across eight Canadian paediatric centres during the COVID-19 pandemic (March 15, 2020 to July 31, 2020) and compare this to the same time period in 2019. Comparing the pre-COVID to the COVID-19 time period, presentation in DKA increased from 36.4% to 55.0% (P

Biallelic pathogenic variants in CYPA24A1 and SLC34A1 are causes of idiopathic infantile hypercalcemia. Pathogenic variants in both may also give rise to hypercalciuria with nephrocalcinosis or nephrolithiasis without previous hypercalcemia (renal group). Our objective was to examine the frequency of CYP24A1 or SLC34A1 variants in children with early hypercalcemia or late-onset hypercalciuria.Forty-one children from 7 centers across Canada were recruited. Local investigations were undertaken. The serum was evaluated by liquid chromatography tandem-mass spectrometry for the ratio of 25-hydroxyvitamin D3 to 24,25-dihydroxyvitamin D3, (25-OH-D3:24,25-(OH)2D3), an elevation pathognomonic for the loss of function of the CYP24A1 enzyme. Mutational analyses were undertaken. Family cascade screening was performed if pathogenic variants were detected in probands.Twenty-nine children had early-onset hypercalcemia; none had elevated 25-OH-D3:24,25-(OH)2D3 or variants. Interestingly, 2 of 12 in the renal group had elevated 25-OH-D3:24,25-(OH)2D3 and presented as preadolescents. In case 1, cascade testing revealed a sibling and parent with asymptomatic pathogenic variants in CYP24A1. Four CYP24A1 pathogenic variants were identified in these 2 probands: 3 have been described in European populations, and 1 is a rare variant in exon 7 (c931delC) that is likely pathogenic. No SLC34A1 pathogenic variants were detected.In Canada, pathogenic variants in CYP24A1 appear to manifest with late-onset hypercalciuria and its sequelae. The 25-OH-D3:24,25-(OH)2D3 ratio is an excellent tool for screening for biallelic pathogenic variants in CYP24A1. We confirm that cascade testing is important for these variants.

This cohort study assesses the risk of diabetic ketoacidosis at the diagnosis of type 1 diabetes among children who participated in the Trial to Reduce Insulin-Dependent Diabetes Mellitus in the Genetically at Risk (TRIGR).

OBJECTIVE The aim of this study was to investigate the frequency of newly diagnosed type 1 diabetes without evidence of autoimmunity and the respective frequencies of ketoacidosis in children, adolescents, and young adults during the coronavirus disease 2019 (COVID-19) pandemic in Germany compared with the previous decade. RESEARCH DESIGN AND METHODS Based on data from the German Diabetes Prospective Follow-up Registry (DPV), we compared data from 715 children, adolescents, and young adults, newly diagnosed with type 1 diabetes during the COVID-19 pandemic in Germany between 1 March and 30 June 2020, with data from 5,428 children, adolescents, and young adults of the same periods from 2011 to 2019. Adjusted differences and relative risks (RRs) of negative β-cell autoantibody test results and diabetic ketoacidosis were estimated using multivariable log-binomial regression analysis. An upper noninferiority test (margin 1%) was applied to evaluate whether the autoantibody-negativity rate in 2020 was not higher than that in 2011 to 2019. RESULTS The estimated frequencies of autoantibody negativity in 2020 and 2011–2019 were 6.6% (95% CI 5.1–8.4) and 7.2% (95% CI 6.5–8.0), respectively, with an absolute difference of −0.68% (90% CI −2.07 to 0.71; Pupper noninferiority = 0.023). The increase of the estimated frequency of diabetic ketoacidosis during the COVID-19 pandemic was similar between autoantibody-negative and -positive type 1 diabetes (adjusted RRs 1.28 [95% CI 0.80–2.05] and 1.57 [1.41–1.75], respectively). CONCLUSIONS This study found no evidence that the COVID-19 pandemic leads to a significantly increased number of new cases with autoantibody-negative type 1 diabetes in children, adolescents, and young adults. In addition, autoantibody-negative type 1 diabetes showed no particular susceptibility to ketoacidosis, neither before nor during the pandemic.

Pediatric diabetes 22(3), 455-462 (2021). doi:10.1111/pedi.13185, Published by Wiley-Blackwell, Oxford [u.a.]

Youth with type 1 diabetes are at high risk for loss to follow-up during the transition from paediatric to adult diabetes care. Our aim was to assess the effect of a communication technology enhanced transition coordinator intervention compared with usual care on clinic attendance among transitioning youth with type 1 diabetes.In this open label, pragmatic clinical trial of youth with type 1 diabetes, aged 17-18 years, transitioning from paediatric to adult diabetes care, the intervention group received support from a transition coordinator who used communication technology and the control group received usual care. The primary outcome was the proportion of individuals that did not attend at least one routine clinic visit in adult diabetes care within 1 year after transfer. Secondary outcomes included diabetes-related clinical outcomes and quality of life measures.There were no baseline differences in age, sex, HbAOur intervention was successful in improving clinic attendance among transitioning youth with type 1 diabetes. Importantly, this programme used simple, readily accessible communication technologies, which increases the sustainability and transferability of this strategy.isrctn.org ISRCTN13459962.

Background and Aims When youth with diabetes transition from pediatric to adult diabetes care, they are at high risk for loss to follow up and worsening glucose control. We aimed to gain insight on how to improve the transition of youth with type 1 diabetes from pediatric to adult diabetes care from the patients' and parents' perspective. Methods We conducted focus groups in youth with type 1 diabetes in transition from pediatric to adult diabetes care and their parents, in Calgary, Alberta, between June and August 2014. Eligibility criteria included: (a) type 1 diabetes; (b) aged 15 to 25 years; (c) have or had received care at the pediatric hospital; and, (d) either pre or post‐transfer; or, (e) parents of recently transferred youth. Purposive sampling was used, and the theoretical framework used was the Integrated Behaviour Model. Participants were asked about positive, negative, or challenging experiences related to diabetes and transition, solutions to challenges, and tools and strategies to improve and better support transition. Thematic analysis was conducted after focus groups were recorded and transcribed. Results Three focus groups were conducted: pre‐transfer youth with diabetes (4 females and 3 males; median age 17.5 years, IQR 1.3 years); post‐transfer young adults with diabetes (2 females and 2 males; median age 23.5 years, IQR 1.2 years); and parents of recently transferred young adults with diabetes (n = 3). Main themes were: (a) communication technology; (b) the need for more transition and diabetes education and preparation during transition; and, (c) the importance and need for social and peer support. Conclusion This study describes specific areas that may improve diabetes transfer and transition from pediatric to adult diabetes care. This information can help inform clinical care delivery for transition and the development of programs, strategies, and interventions to improve transition care.

Objectives To describe clinical presentation and long-term outcomes in a large cohort of children diagnosed with thiamine-responsive megaloblastic anemia (TRMA)-related diabetes. Methods Data from the Diabetes Patienten Verlaufsdokumentation (DPV) and Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference (SWEET) registries were used to identify cases. Complementary information was collected through a chart review of each case. Descriptive analyses with medians and interquartile ranges and numbers (proportions) were tabulated. Results We identified 23 cases (52% male) in the 2 registries. Eighteen (78%) had genetic confirmation of TRMA. Median age at diabetes onset was 1.4 (quartiles 0.8 to 3.6) years and median age at initiation of thiamine treatment was 5.9 (2.4 to 12.4) years. At their most recent visit, patients’ median age was 14.3 (8.1 to 17.5) years, glycated hemoglobin level was 6.9% (6.1% to 7.9%), insulin dose was 0.9 (0.4 to 1.2) units/kg per day and thiamine dose was 200 (100 to 300) mg/day. Three patients were not treated with insulin or antidiabetic drugs. There was no difference in diabetes outcomes in patients with initiation of thiamine ≤1 year after diabetes onset compared to patients with initiation of thiamine >1 year after diabetes onset. Conclusions This is the longest case series of pediatric TRMA-related diabetes reported to date. Diabetes onset often occurs several years before initiation of thiamine supplementation. Early initiation of thiamine (within 1 year of diabetes onset) was not linked to improved diabetes outcome. However, the role of thiamine in pancreatic function needs further assessment. Patients with TRMA-related diabetes maintained good glycemic control even after 9 years (median) of follow up.

OBJECTIVES: Growth hormone (GH) therapy is an effective treatment in addressing growth failure in children with GH deficiency (GHD). It has also been increasingly used in non-GH deficient (nGHD) conditions. We sought to report the growth response of GHD and nGHD patients who received GH therapy at a tertiary care center. METHODS: Data was collected from health records of patients followed in the endocrinology clinic at Alberta Children’s Hospital, Calgary, Canada, from 2005 to 2019, and used to analyze clinical responses based on indication for GH treatment. RESULTS: A total of 167 patient records (87 males and 80 females) were used for analysis. The average age at the start of GH therapy was 7.3 years (range 0.25 to 16.98 yrs). 74 patients were in the GHD group while 93 were nGHD. Of the patients in the nGHD group, the most common diagnosis were: idiopathic short stature (ISS)(n=45), Turner syndrome (TS)(n=26), and Prader Willi Syndrome (PWS)(n=8). The mean height velocity (HV) in year 1 was highest in the GHD group at 11.68 cm/year (n= 62, sd = 5.93), followed by ISS at 9.41cm/year (n = 52, sd = 4.34). The mean first year HV of those who had received chemotherapy (n= 5, mean = 5.48, sd = 1.92) or had Turner syndrome (n= 24, mean = 7.20, sd = 2.15) was significantly lower than both the GHD and ISS groups. GH peak during a GH stimulation test at baseline was not correlated to the first year height velocity while on GH treatment. However there was a negative linear correlation between baseline IGF1 level and first year height velocity (Spearman’s rho = 0.312216, p-value= 0.01516). Age at GH initiation was negatively correlated with height velocity during GH treatment. Height velocity over time decreased sharply from year 1 to year 3, and became stable for the remaining years of GH therapy. For the entire group, HV for years 1-5 was 9.81 (sd=4.83), 7.40 (sd=2.89), 6.29 (sd=2.38), 5.92 (sd=2.56), 5.66 (sd=2.51). There is no significant correlation between GH dose and height velocity response after adjusting for diagnosis. CONCLUSION: In our population, the response to GH therapy was consistent with those reported in the literature. Response to GH therapy was not associated with GH peak on stimulation but rather to baseline IGF-1 level and age at initiation. Although peak GH to stimulation is required to obtain public funding for GH therapy, these findings demonstrate that GH stimulation test results may not indicate which patients may benefit the most from GH therapy. Follow-up until final adult height will allow us to have a better understanding of the efficacy of GH therapy in patients with both GHD and nGHD conditions.

IntroductionTransition to adult care is a challenging and complex process for youth with special healthcare needs. We aim to compare effectiveness of a patient navigator service in reducing emergency room (ER) use among adolescents with chronic health conditions transitioning to adult care.Methods and analysisPragmatic randomised controlled trial parallel group design comparing ER visit rates between patients with access to a personalised navigator intervention compared with usual care. Unit of randomisation is the patient. Treatment assignment will not be blinded. Embedded qualitative study to understand navigator’s role and cost analysis attributable to the intervention will be performed. Patients aged 16–21 years, followed within a chronic disease clinic, expected to be transferred to adult care within 12 months and residing in Alberta during study period will be recruited from three tertiary care paediatric hospitals. Sample size will be 300 in each arm. Navigator intervention over 24 months is designed to assist participants in four domains: transition preparation, health system brokering, socioeconomic determinants of health and self-management. Primary outcome is ER visit rate during observation period. Secondary outcomes are ambulatory and inpatient care utilisation measures, as well as Transition Readiness Assessment Questionnaire score, and Short-Form Health Survey 12 (SF-12) score at 6 and 18 months post-randomisation. Poisson regression will compare rates of ER/urgent care visits between navigator and control participants, using intention to treat principle. Cost analysis of the intervention will be conducted. Thematic analysis will be used to identify perceptions of stakeholders regarding the role of navigators.Ethics and disseminationEthics approval was obtained from the University of Calgary Conjoint Health Research Ethics Board (REB #162561) and the University of Alberta Health Research Ethics Board (Pro00077325). Our team is composed of diverse stakeholders who are committed to improving transition of care who will assist with dissemination of results.Trial registration numberNCT03342495.

Background Newborn premature infants are susceptible to development of relative adrenal insufficiency following transition from fetal to extrauterine life. However, the best diagnostic test for adrenal insufficiency in neonates has yet to be developed. Objectives and Methods The aim of this study was (1) to assess the feasibility of obtaining sufficient saliva sample to allow measurement of cortisol by liquid chromatography coupled to tandem mass spectrometry and (2) to assess the correlation, if any, between salivary and serum cortisol in preterm infants of ≤32 weeks' gestational age at birth. Results Samples for 230 paired serum and saliva cortisol levels from 90 preterm infants were analyzed. 87.5% of samples collected had sufficient salivary volumes for measurement. Despite being statistically significant (p Conclusion Salivary free cortisol measurement is feasible but cannot be used to accurately reflect serum total cortisol. Further studies comparing salivary free cortisol to serum free cortisol and establishing normative data are needed before salivary cortisol can be used for diagnostic purposes.

The measurement of corneal nerve fibre length (CNFL) by in vivo corneal confocal microscopy serves as a biomarker for the presence of diabetic distal symmetric polyneuropathy (DSP). We aimed to determine the threshold for abnormal CNFL change, its prevalence in T1D and T2D, and if this biomarker could predict DSP progression. Data from 622 diabetes patients (424 T1D and 198 T2D) and 204 nondiabetic controls were examined as part of a 5-centre multinational consortium study. Patients had at least 1-year of follow-up data and were classified with Rapid CNFL (RCNFL) loss if the change in CNFL was beyond the 5thpercentile of the controls. Controls were 38±20 y, had a median of 3 follow-up visits over a median of 3.0 y, baseline CNFL of 16±4 mm/mm2, and a mean annual change in CNFL of -0.1%[90% CI, -5.9-5.0%]. RCNFL loss was defined by the 5th percentile value of -6% or greater loss. T1D patients were 40±19 y, had a median of 3 visits over a median of 4.4 y, baseline CNFL of 13.5±4.3 mm/mm2 and had a mean annual change in CNFL of -0.8%[90% CI, -14.0-9.9%]. T2D patients were 60±8 y, had a median of 3 visits over a median of 5.3 y, baseline CNFL of 13.8±4.4 mm/mm2 and a mean annual change in CNFL of -0.2%[90% CI, -14.1-14.3%]. Prevalence of RCNFL loss was similar between T1D (64(16.0%)) and T2D (37(19.4%), p=0.31). Baseline CNFL was not different between cases with RCNFL loss (14.3±4.2 mm/mm2) and diabetes controls (13.5±4.3 mm/mm2) (p=0.073). Cases were more likely to have DSP at baseline (47, (47%) vs. 144, (30%), p=0.001). During follow-up, CNFL decreased in cases (-3.5 mm/mm2[-5.7, -1.5] vs. 0.59 mm/mm2 [-1.3, 2.4], p>0.001). Cases showed DSP progression measured by changes in sural nerve conduction velocity (0.0 m/s [-1.2, 2.4] vs. 0.2 m/s [-1.1, 5.0]. p=0.027) and peroneal conduction velocity (-1.1 m/s [-3.6, 0.9] vs. -0.6 [-2.8, 1.5], p=0.001) compared to diabetes controls. Rapid CNFL loss occurs in over 16% of diabetes patients and appears to predict those at highest risk for DSP progression. Disclosure E.J.H. Lewis: Board Member; Spouse/Partner; Nutarniq Corp. Employee; Self; Nutarniq Corp. L. Lovblom: None. M. Ferdousi: None. M. Jeziorska: None. D. Pacaud: Other Relationship; Self; Novo Nordisk A/S, Sandoz, TOLMAR. N. Pritchard: None. R.M. Shtein: None. N. Efron: None. M. Tavakoli: None. V. Bril: Advisory Panel; Self; Akcea Therapeutics, Alexion Pharmaceuticals, Inc., Alnylam, CSL Behring. Consultant; Self; Pfizer Inc. Research Support; Self; Baxter, Biogen, Grifols, UCB, Inc. R.A. Malik: None. B.A. Perkins: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk Inc., Sanofi. Funding National Institutes of Health (1DP3DK104386-01)

Corneal Nerve Fibre Length (CNFL) reasonably identifies the presence of neuropathy in patients with T1D and T2D. In this longitudinal diagnostic study, we aimed to determine its ability to predict future neuropathy. Among 998 participants with diabetes, we examined the 387 who did not have neuropathy at baseline and who had follow-up in a 5-centre multinational consortium study. Participants underwent corneal nerve quantification and clinical and electrophysiological examination for neuropathy at baseline and in scheduled follow-up. Predictive validity and diagnostic thresholds were determined using time-dependent receiver operating characteristic (ROC) curves that accounted for censoring, and used baseline and time-updated CNFL. Estimates were derived in the T1D subcohort and validated in the T2D subcohort. The 387 participants had mean follow-up of 4.8 years (interquartile range 3-7y). 288 had T1D (baseline mean age 35±17 years and A1c 8.2±1.5%) and 99 had T2D (baseline age 59±8 years and A1c 7.3±1.1%). New onset neuropathy occurred in 85 participants (22%; incidence rate 5.05 events per 100 person years). The crude area under the ROC curve (AUC) for CNFL was 0.64 (95% CI 0.56-0.73, p=0.001) in the T1D derivation set, which was confirmed in the T2D validation set (AUC 0.69, 95% CI 0.57-0.81, p=0.002). In the combined cohort, time-dependent ROC curves were generated for 2, 4, 6, and 8 years; AUC ranged from 0.67 to 0.71 for baseline CNFL, and 0.66 to 0.68 for time-updated CNFL. The optimal diagnostic threshold for baseline CNFL was 14.1mm/mm2 (sensitivity 67%, specificity 63%, 1ikelihood ratio (LR) positive 1.8, LR negative 0.5, Cox proportional hazard rate ratio 2.79, p Disclosure B.A. Perkins: Advisory Panel; Self; Abbott, Boehringer Ingelheim International GmbH, Boehringer Ingelheim International GmbH, Insulet Corporation. Research Support; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Abbott, Boehringer Ingelheim International GmbH, Lilly Diabetes, Medtronic, Novo Nordisk Inc., Sanofi. L. Lovblom: None. V. Bril: Advisory Panel; Self; Akcea Therapeutics, Alexion Pharmaceuticals, Inc., Alnylam, CSL Behring. Consultant; Self; Pfizer Inc. Research Support; Self; Baxter, Biogen, Grifols, UCB, Inc. M. Ferdousi: None. A. Orszag: None. K. Edwards: None. N. Pritchard: None. A.W. Russell: None. C. Dehghani: None. D. Pacaud: Other Relationship; Self; Novo Nordisk A/S, Sandoz, TOLMAR. K. Romanchuk: None. J. Mah: None. M. Jeziorska: None. A. Marshall: None. R.M. Shtein: None. R. Pop-Busui: Consultant; Self; Novo Nordisk A/S. Research Support; Self; AstraZeneca. Other Relationship; Self; American Diabetes Association. S.I. Lentz: None. A.J. Boulton: None. M. Tavakoli: None. N. Efron: None. R.A. Malik: None. Funding National Institutes of Health

Background: The transition from pediatric to adult diabetes care is a vulnerable period for youth with diabetes. During transition, youth with diabetes are at high risk for loss to follow-up, worsening glycemic control, and increased hospitalizations. Objective: Our objective was to assess the effect of a technology enhanced transition coordinator on loss to follow-up in youth with diabetes transitioning from pediatric to adult diabetes care. Methods: This open label, pre-post pragmatic clinical trial, assessed the effect of a technology enhanced transition coordinator in transitioning young adults with diabetes from pediatric to adult diabetes care. Our primary outcome was the rate of loss to follow-up defined as no outpatient diabetes appointments in the one year following transfer. The usual care (control) cohort were youth with diabetes who received usual care (i.e., transition preparation during pediatric diabetes appointments prior to transfer). The intervention cohort received the usual care and had a transition coordinator who assisted them through the transition period with regular, per protocol contact, by texting, emailing, Twitter®, and/or postings on a private Facebook® page. Results: Baseline average hemoglobin A1c was not different between the intervention cohort [number (n) = 101, 47.5% females] versus the usual care cohort (n= 209, 49.3% female) [8.9 ± 2.0 standard deviation (SD) versus 9.1 ± 2.4 SD, p=0.28] in the year prior to transfer. In the year following transfer, 49.3% of young adults in the usual care cohort versus 11.8% of young adults in the intervention group did not attend any outpatient diabetes appointments (p< 0.01) in the year following transfer. Conclusions: Our technology enhanced transition coordinator intervention was successful in reducing loss to follow-up in transitioning young adults with diabetes. Importantly, this program used simple readily accessible technologies which increases the transferability and sustainability of this intervention. Disclosure S. Butalia: None. A. McGuire: None. S. Crawford: None. D. Dyjur: None. J. Mercer: None. D. Pacaud: Other Relationship; Self; Novo Nordisk A/S, Sandoz, TOLMAR. Funding Lawson Foundation

OBJECTIVE Corneal nerve fiber length (CNFL) represents a biomarker for diabetic distal symmetric polyneuropathy (DSP). We aimed to determine the reference distribution of annual CNFL change, the prevalence of abnormal change in diabetes, and its associated clinical variables. RESEARCH DESIGN AND METHODS We examined 590 participants with diabetes (399 with type 1 diabetes [T1D] and 191 with type 2 diabetes [T2D]) and 204 control patients without diabetes with at least 1 year of follow-up and classified them according to rapid corneal nerve fiber loss (RCNFL) if CNFL change was below the 5th percentile of the control patients without diabetes. RESULTS Control patients without diabetes were 37.9 ± 19.8 years old, had median follow-up of three visits over 3.0 years, and mean annual change in CNFL was −0.1% (90% CI −5.9% to 5.0%). RCNFL was defined by values exceeding the 5th percentile of 6% loss. Participants with T1D were 39.9 ± 18.7 years old, had median follow-up of three visits over 4.4 years, and mean annual change in CNFL was −0.8% (90% CI −14.0% to 9.9%). Participants with T2D were 60.4 ± 8.2 years old, had median follow-up of three visits over 5.3 years, and mean annual change in CNFL was −0.2% (90% CI −14.1% to 14.3%). RCNFL prevalence was 17% overall and was similar by diabetes type (64 T1D [16.0%], 37 T2D [19.4%], P = 0.31). RNCFL was more common in those with baseline DSP (47% vs. 30% in those without baseline DSP, P = 0.001), which was associated with lower peroneal conduction velocity but not with baseline HbA1c or its change over follow-up. CONCLUSIONS An abnormally rapid loss of CNFL of 6% per year or more occurs in 17% of diabetes patients. RCNFL may identify patients at highest risk for the development and progression of DSP.

Objectives The aim of this work was to survey how well adolescents with type 1 diabetes mellitus (T1D) of legal driving age understand the risks associated with driving with diabetes and report adherence to recommendations. Methods This study was a cross-sectional survey of 191 adolescents, 14 to 18 years of age, with T1D. Results The average (standard deviation [SD]) glycated hemoglobin of respondents with a learner's or a driver's license was 9.0% (SD, 1.9%) and 8.9% (SD, 1.9%), respectively (p=0.91). The proportions of adolescents with a learner's or a driver's license who almost always or always checked their blood glucose prior to driving was 69% and 41%, respectively (p=0.01). Eighteen percent of adolescents with a learner's license and 41% with a driver's license experienced hypoglycemia while driving. The average number of weekly hypoglycemic events in each group was 2.0 (SD, 1.4) and 2.3 (SD, 2.0), respectively. There was a higher reported frequency of weekly mild hypoglycemic events between drivers who reported pulling over at least once while driving due to symptoms of hypoglycemia (3.25±2.38) and those who reported never having pulled over for hypoglycemia (1.87±1.31) (p=0.012). Respondents with a learner's license reported higher adherence to guidelines than those with a full license. Conclusions Clinical education needs to reinforce adherence to recommendations, particularly checking blood glucose or wearing a continuous glucose monitor prior to driving, for all adolescents of driving age. The frequency of mild hypoglycemic events per week is associated with self-reported hypoglycemic events while driving.

Objective To survey adolescents with type 1 diabetes mellitus (T1DM) about their knowledge and application of harm-reduction recommendations when they engage in alcohol and other illicit substance use. Methods Cross-sectional survey and chart review of adolescents with T1DM aged 13 to 18 years. Results One hundred and ninety patients were approached and 164 were included in the analysis. Mean age was 15.6 years (standard deviation [SD]=1.5). Fifty-one per cent were male. Of those who reported consuming alcohol, 95% knew that they should have a friend or parent check their blood glucose in the middle of the night after drinking but only 62% reported actually doing this in practice. Similarly, 98% reported knowing that they should wear a medic alert identification but only 79% reported actually doing this. Of those who reported consuming cannabis, 14% reported forgetting to check blood glucose and 14% reported forgetting insulin when using cannabis. From the chart review, a significantly lower proportion of adolescents reported substance use during their clinic visits (alcohol 26%, tobacco 19%, illicit substance 25%) compared to the self report in the survey (alcohol 55%, tobacco 30%, illicit substance 32%). Conclusions Adolescents' knowledge of harm-reduction practices for the use of alcohol and other illicit substances is not always put to practice. Motivating adolescents to use their knowledge in practice is an important area to improve in diabetes self-management. Those who reported engaging in substance use in the survey had not always reported use during interactions with health care providers. This emphasizes the need for unbiased, universal education of all adolescents in the clinic.

Background Transition to adult care represents a vulnerable period for young people with special health care needs as they navigate multiple life transitions and developmental issues. Patient navigators are a promising intervention designed to facilitate the transfer from pediatric to adult care. However, consistent definitions, key tasks, roles and responsibilities are lacking in guiding the scope of practice and the implementation of patient navigators. Methods Fundamental qualitative description was utilized in this study to identify perceptions from health care providers about implementing a patient navigator service for young people with special health care needs in transition to adult care. A purposive sample of health care providers with a variety of backgrounds within pediatric and adult systems in Alberta, Canada were recruited. Semi-structured interviews with participants were analyzed using thematic analysis to inductively identify perceptions regarding the role of patient navigators. Results A total of 43 health care providers highlighted the need for a patient navigator service to encompass 4 key stages for young people with special health care needs transitioning from pediatric to adult services: (1) identification of young people with special health care needs and families requiring support, (2) preparation for transfer, (3) health system navigation and, (4) post-transfer support. Conclusions The results of this qualitative study provide guidance for the development of patient navigator interventions for young people with special health care needs, as well as provide support for current transition services offered across Canada. Electronic supplementary material The online version of this article (10.1186/s12913-019-4227-6) contains supplementary material, which is available to authorized users.

OBJECTIVE: To assess the prevalence of underweight (UW), overweight (OW), and obesity in children and adolescents with type 1 diabetes (T1D).METHODS: An international cross-sectional study including 23 026 T1D children (2-18 years, duration of diabetes ≥1 year) participating in the SWEET prospective, multicenter diabetes registry. Body mass index SD score (BMI-SDS) was calculated using the World Health Organization BMI charts. Children were categorized as UW (BMI-SDS +2SD). Hierarchic regression models were applied with adjustment for sex, age, and duration of diabetes.RESULTS: The prevalence of UW, OW, and obesity was: 1.4%, 22.3%, and 7.3% in males and 0.6%, 27.2%, and 6.8% in females. Adjusted BMI-SDS was significantly higher in females than in males (mean ± SEM: 0.54 ± 0.05 vs 0.40 ± 0.05, P CONCLUSIONS: The high rate of OW and obesity (31.8%) emphasize the need for developing further strategies to prevent and treat excess fat accumulation in T1D.

Objectives Insulin pump therapy is a valuable, but costly approach, with public funding in Alberta for eligible individuals since 2013. The Provincial Insulin Pump Therapy Program Clinical Advisory Committee has revised and updated the clinical criteria, integrating current literature, best practice and feedback from clinicians. The objective was to develop criteria that would: 1) optimize safety and effectiveness of insulin pump therapy, while 2) carefully stewarding resources available to care for people with type 1 diabetes. Methods The Clinical Advisory Committee comprised health-care professionals with expertise in pump therapy and included adult and pediatric endocrinologists, an internist, a pediatrician, certified pump trainers, diabetes educators and clinic managers. The group meets regularly by teleconference. Decisions are made by consensus. Results Indications for insulin pump therapy for adults and children with insulin-deficient diabetes were divided into 4 hierarchical levels: 1) problematic hypoglycemia, inability to achieve acceptable control or progressive complications; 2) unpredictable activity, dawn phenomenon or children for whom use of multiple daily injections is not appropriate; 3) individual preference and 4) clinical exception, with priority given to indications with clear evidence of benefit. The criteria emphasize the importance of: 1) adequate education in diabetes self-management; 2) adequate trial of flexible insulin therapy with modern analogues and 3) evidence of active, safe diabetes self-management. Tools to facilitate effective and efficient annual review and surveillance were developed incorporating biological, behavioural evaluation and self-reflection to provide a framework for program evaluation. The recommendations were implemented in January 2019. Conclusions The process and revised criteria may be valuable for jurisdictions considering how to develop and implement a publicly funded insulin pump program.

To determine if physical activity is linked to cardiovascular biomarkers in preschool children at risk, we need information on these biomarkers in healthy normal-weight children. In this population, multi-level modelling analyses found no correlation between accelerometer recorded physical activity and fasting lipids, adiponectin, or insulin sensitivity. Exploratory analyses found positive correlations between adiponectin and time spent in light physical activity, and between triglyceride and time spent in sedentary behaviour; these findings need to be confirmed in longitudinal prospective studies.

Background Type 1 Diabetes Mellitus Virtual Patient Network (T1DM-VPN) is a private Facebook group for youths with type 1 diabetes mellitus (T1DM) in Canada intended to facilitate peer-to-peer support. It was built on the finding that stigma is prevalent among youth with T1DM and impedes self-management. Objective We aim to determine if T1DM-VPN provides support as intended and to ascertain what type of members provide support. Specifically, we will (1) identify text consistent with any one of 5 social support categories, (2) describe the network by visualizing its structure and reporting basic engagement statistics, and (3) determine whether being a designated peer leader is related to a member’s centrality (ie, importance in the network) and how frequently they offer social support. Methods We will manually extract interaction data from the Facebook group (posts, comments, likes/reactions, seen) generated from June 21, 2017 (addition of first member), to March 1, 2020. Two researchers will independently code posts and comments according to an existing framework of 5 social support categories—informational, emotional, esteem, network, and tangible—with an additional framework for nonsocial support categories. We will calculate how frequently each code is used. We will also report basic engagement statistics (eg, number of posts made per person-month) and generate a visualization of the network. We will identify stable time intervals in the history of T1DM-VPN by modeling monthly membership growth as a Poisson process. Within each interval, each member’s centrality will be calculated and standardized to that of the most central member. We will use a centrality formula that considers both breadth and depth of connections (centrality = 0.8 × total No. of connections + 0.2 × total No. of interactions). Finally, we will construct multivariate linear regression models to assess whether peer leader status predicts member centrality and the frequency of offering social support. Other variables considered for inclusion in the models are gender and age at diagnosis. Results T1DM-VPN was launched in June 2017. As of March 1, 2020, it has 196 patient-members. This research protocol received ethics approval from the McGill University Health Centre Research Ethics Board on May 20, 2020. Baseline information about each group member was collected upon addition into the group, and collection of interaction data is ongoing as of May 2020. Conclusions This content analysis and social network analysis study of a virtual patient network applies epidemiological methods to account for dynamic growth and activity. The results will allow for an understanding of the topics of importance to youth with T1DM and how a virtual patient network evolves over time. This work is intended to serve as a foundation for future action to help youth improve their experience of living with diabetes. International Registered Report Identifier (IRRID) PRR1-10.2196/18714

ISPAD Clinical Practice Consensus Guidelines 2018 : Management and support of children and adolescents with type 1 diabetes in school

The measurement of corneal nerve fibre length (CNFL) by in vivo corneal confocal microscopy is a biomarker for the presence of diabetic sensorimotor polyneuropathy (DSP). We aimed to determine the reference distribution of annual CNFL change, its prevalence in T1D and T2D, and its clinical predictors. We examined longitudinal data from 94 nondiabetic controls and 297 diabetes participants (224 T1D and 73 T2D) from an ongoing multi-centre NIH-funded study of IVCCM in diabetes. Participants were included if they had at least 1-year of follow-up data and were classified as progressors with “rapid corneal nerve fibre loss” (RCNFL) if the loss of CNFL was beyond the 5th percentile (-14%/y) of the nondiabetic controls. Nondiabetic controls were 43.0±15.8 y, had a median of 2 follow-up visits over a median of 2 y, baseline CNFL of 15.4±4.2 mm/mm2, and the median annual change in CNFL was -1.7%[90% CI, -14.3 to 30.9%]. Diabetes participants were 49.6±15.5 y, had a median of 3 visits over a median of 2 y, baseline CNFL of 14.3±4.4 mm/mm2 and the median annual change in CNFL was 1.8%[90% CI, -26.1 to 25.0%]. There were 33(11.1%) cases of RCNFL in the diabetes sub-cohort, which was comparable between T1D (26(11.6%)) and T2D (7(9.6%)). Progressors did not differ from non-progressors for baseline levels of age, sex, BMI, HbA1c or CNFL levels. However, progressors were more likely to have baseline DSP (16(50%) vs. 83(32%), p=0.048), lower cooling detection threshold (21.3 C±8.5 vs. 25.3 C±7.2, p=0.048) and lower heart rate variability (26.3±13.1 vs. 38.2±25.4, p=0.036). A more rapid loss of CNFL (RCNFL) exceeding 14%/y occurs in ∼11% of diabetes patients. This more rapid of corneal nerves may identify patients at highest risk for the development or progression of DSP. Disclosure E.J.H. Lewis: Employee; Self; Nutarniq Corp. M. Tavakoli: None. L. Lovblom: None. E.M. Halpern: None. M. Jeziorska: None. D. Pacaud: Research Support; Self; Eli Lilly and Company, Novo Nordisk Inc., National Institute of Diabetes and Digestive and Kidney Diseases, Versartis, Inc. N. Pritchard: Other Relationship; Self; JDRF, NHMRC. R.M. Shtein: None. N. Efron: None. V. Bril: Consultant; Self; Alexion Pharmaceuticals, Inc.. Research Support; Self; CSL Behring, Grifols. Advisory Panel; Self; CSL Behring. Consultant; Self; Grifols. Research Support; Self; Shire. Advisory Panel; Self; Pfizer Inc.. R.A. Malik: None. B.A. Perkins: Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH, Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc., Abbott. Speaker's Bureau; Self; Abbott, Janssen Pharmaceuticals, Inc.. Advisory Panel; Self; Insulet Corporation. Speaker's Bureau; Self; Insulet Corporation, Dexcom, Inc..

BACKGROUND: Youth with chronic conditions may engage in risky behaviour to the same, if not higher, degree as their healthy peers. OBJECTIVES: To determine the prevalence of alcohol, tobacco, cannabis and illicit substance use in adolescents with type 1 diabetes (T1DM) compared to a general adolescent population. METHODS: Cross-sectional survey of adolescents with T1DM (13 to 18 years). A published contemporary Canadian youth survey on use of alcohol, tobacco and illicit drugs was used as data representative of the general adolescent population. Outcome measures between the T1DM and general group were compared using Chi-square and Fisher’s exact test where appropriate. RESULTS: One hundred and sixty-four adolescents with T1DM (mean 15.6 years [SD 1.5]; 51.3% male) were participated. The proportions of adolescents with T1DM who have tried substances were: alcohol 51.8%, tobacco 27.4%, cannabis 22.6% and other illicit substances 7.3%. Compared to the general population (n=3469), there were no significant differences in the proportion of adolescents that reported ever consuming alcohol, tobacco or cannabis. Reported illicit substance use was significantly lower in adolescents with T1DM compared to general population (7.3% versus 36.0%, P

BACKGROUND A paucity of reports in the literature exists concerning the co-existence between autism spectrum disorder (ASD) and type 1 diabetes (T1D). OBJECTIVE To compare clinical characteristics, diabetes management and metabolic control in youth with T1D and ASD (T1D-ASD) with youth without ASD (T1D-non ASD). METHODS Using the German/Austrian diabetes patient follow-up registry, this study analyzed aggregated data from the last available year of observation for each patient with T1D, ages 1-20 with consistent data on insulin regimen and glycated hemoglobin (A1C), between January, 2005 and March, 2017. RESULTS From 61 749 patients, 150 (0.24%) were identified as T1D-ASD. Non-adjusted comparisons showed similar results for mean age at onset and duration of diabetes, but not for gender (male: T1D-ASD: 85.3%; T1D-non ASD: 52.8%; P

Aims/hypothesis Small cohort studies raise the hypothesis that corneal nerve abnormalities (including corneal nerve fibre length [CNFL]) are valid non-invasive imaging endpoints for diabetic sensorimotor polyneuropathy (DSP). We aimed to establish concurrent validity and diagnostic thresholds in a large cohort of participants with and without DSP. Methods Nine hundred and ninety-eight participants from five centres (516 with type 1 diabetes and 482 with type 2 diabetes) underwent CNFL quantification and clinical and electrophysiological examination. AUC and diagnostic thresholds were derived and validated in randomly selected samples using receiver operating characteristic analysis. Sensitivity analyses included latent class models to address the issue of imperfect reference standard. Results Type 1 and type 2 diabetes subcohorts had mean age of 42 ± 19 and 62 ± 10 years, diabetes duration 21 ± 15 and 12 ± 9 years and DSP prevalence of 31% and 53%, respectively. Derivation AUC for CNFL was 0.77 in type 1 diabetes (p

OBJECTIVE: To describe the association between height, demographics, and treatment in youths with type 1 diabetes participating in an international network for pediatric diabetes centers (SWEET). METHODS: Data were collected from 55 centers with documented patients' height. All subjects below 20 years of age, diabetes duration >1 year, and without celiac disease were included. World Health Organization growth charts were used to calculate height and body mass index z-scores. Multiple hierarchic regression models adjusting for known confounders were applied. RESULTS: Data on 22 941 subjects (51.8% male) were analyzed with a median and interquartile range for age 14.8 years (11.2, 17.6), diabetes duration 5.6 years (3.1, 8.9), and height z-score 0.34 (-0.37, 1.03). Children were taller in the youngest age groups: adjusted height z-scores of 0.31 (±0.06) and 0.39 (±0.06), respectively; with shorter diabetes duration (three injections/day and 0.19 ± 0.06 [0-3 injections daily]), respectively. High hemoglobin A1c (HbA1c) and low to normal weight were associated with a lower height z-score. Trends were identical in all models except for gender. No gender differences were found except in the final height model where females exhibited higher z-score than males. CONCLUSION: For youths treated at centers offering modern diabetes management, major growth disturbances are virtually eliminated. For children with a young age at onset, high HbA1c, injections, and/or non-intensive diabetes, treatment still requires attention in order to attain normal growth.

OBJECTIVE Corneal confocal microscopy is a novel diagnostic technique for the detection of nerve damage and repair in a range of peripheral neuropathies, in particular diabetic neuropathy. Normative reference values are required to enable clinical translation and wider use of this technique. We have therefore undertaken a multicenter collaboration to provide worldwide age-adjusted normative values of corneal nerve fiber parameters. RESEARCH DESIGN AND METHODS A total of 1,965 corneal nerve images from 343 healthy volunteers were pooled from six clinical academic centers. All subjects underwent examination with the Heidelberg Retina Tomograph corneal confocal microscope. Images of the central corneal subbasal nerve plexus were acquired by each center using a standard protocol and analyzed by three trained examiners using manual tracing and semiautomated software (CCMetrics). Age trends were established using simple linear regression, and normative corneal nerve fiber density (CNFD), corneal nerve fiber branch density (CNBD), corneal nerve fiber length (CNFL), and corneal nerve fiber tortuosity (CNFT) reference values were calculated using quantile regression analysis. RESULTS There was a significant linear age-dependent decrease in CNFD (−0.164 no./mm2 per year for men, P < 0.01, and −0.161 no./mm2 per year for women, P < 0.01). There was no change with age in CNBD (0.192 no./mm2 per year for men, P = 0.26, and −0.050 no./mm2 per year for women, P = 0.78). CNFL decreased in men (−0.045 mm/mm2 per year, P = 0.07) and women (−0.060 mm/mm2 per year, P = 0.02). CNFT increased with age in men (0.044 per year, P < 0.01) and women (0.046 per year, P < 0.01). Height, weight, and BMI did not influence the 5th percentile normative values for any corneal nerve parameter. CONCLUSIONS This study provides robust worldwide normative reference values for corneal nerve parameters to be used in research and clinical practice in the study of diabetic and other peripheral neuropathies.

Diabetes requiring insulin is increasingly common and likely to impact students in most, if not all, schools. Diabetes and its complications have major personal, social and economic impact, and improved diabetes control reduces the risk of both short- and long-term complications. Evidence shows that more intensive management of diabetes - through frequent blood glucose monitoring, insulin administration with injections and/or insulin pumps, and careful attention to diet and exercise - leads to better control. Since children spend 30 to 35 hours per week at school, effectively managing their diabetes while there is integral to their short- and long-term health. The Canadian Paediatric Society and the Canadian Pediatric Endocrine Group recommend that minimum standards for supervision and care be established across Canada to support children and youth with type 1 diabetes in schools. These recommendations are derived from evidence-based clinical practice guidelines, with input from diabetes care providers from across Canada, and are consistent with the Canadian Diabetes Association's Guidelines for the Care of Students Living with Diabetes at School.Chez les enfants, la présence d’un diabète nécessitant l’insuline pour traitement est de plus en plus fréquente. De fait, il est fort probable que la majorité des écoles canadiennes ait au moins un élève touché par cette maladie. Le diabète et ses complications ont des répercussions personnelles, sociales et économiques majeures. Cependant, une meilleure maîtrise du diabète réduit les risques de complications à court et long terme. Il a été démontré qu’une prise en charge plus intensive du diabète – par une surveillance régulière de la glycémie, l’administration d’insuline par injection ou pompe à insuline et une attention particulière à l’alimentation et à l’activité physique – en facilite la maîtrise. Comme les enfants passent de 30 à 35 heures par semaine à l’école, il est essentiel pour leur santé que la prise en charge de leur diabète y soit efficace. La Société canadienne de pédiatrie et le Groupe canadien d’endocrinologie pédiatrique recommandent d’établir des normes minimales pancanadiennes de supervision et de soins pour aider les enfants et les adolescents atteints de diabète de type 1 dans les écoles. Ces recommandations ont été inspirées de lignes directrices de pratique clinique fondées sur des données probantes et de la contribution des cliniciens du domaine des soins en diabète pédiatrique de tout le Canada. Elles respectent les