Very severe hypertriglyceridemia complicating pediatric acute lymphoblastic leukemia treatment: a call for management guidelines.

OBJECTIVES: Severe and very severe hypertriglyceridemia although rare within the pediatric population occur more often among oncology patients, secondary to chemotherapeutic agents. Currently there exists minimal literature to guide management of severe hypertriglyceridemia among pediatric patients. Very-low-fat dietary restriction should be considered over nil per os (NPO) for initial management of severe hypertriglyceridemia in stable pediatric patients. Pediatricians caring for oncology patients must consider chylomicronemia as a potential etiology for presenting symptoms. Pediatric severe hypertriglyceridemia management guidelines are needed as pediatricians must currently rely on anecdotal experiences for management decisions. CASE PRESENTATION: Three children receiving treatment for acute lymphoblastic leukemia required hospitalization for very severe hypertriglyceridemia. Management varied among the cases but included: NPO or very-low-fat diet, insulin, intravenous fluids, fibrates, and omega-3 fatty acids. CONCLUSIONS: These cases suggest that pediatric severe hypertriglyceridemia management, in the absence of pancreatitis should allow a very-low-fat diet initially rather than NPO followed by pharmacologic therapies.

The Resistance Exercise in Already Active Diabetic Individuals (READI) Randomized Clinical Trial.

CONTEXT: Resistance exercise training (strength training) and aerobic exercise training are both recommended for people with type 1 diabetes, but it is unknown whether adding resistance exercise provides incremental benefits in people with this condition who already perform aerobic exercise regularly. OBJECTIVE: This work aimed to evaluate the incremental effect of resistance training on glycated hemoglobin A1c (HbA1c), fitness, body composition, and cardiometabolic risk factors in aerobically active people with type 1 diabetes. METHODS: The Resistance Exercise in Already-active Diabetic Individuals (READI) trial (NCT00410436) was a 4-center, randomized, parallel-group trial. After a 5-week run-in period with diabetes management optimization, 131 aerobically active individuals with type 1 diabetes were randomly assigned 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 counseling throughout. Exercise training was 3 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. RESULTS: 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 to 0.18]). Waist circumference decreased more in INT than CON after 6 months (P = .02). Muscular strength increased more in INT than in CON (P < .001). There were no intergroup differences in hypoglycemia or any other variables. CONCLUSION: Adding resistance training did not affect glycemia, but it increased strength and reduced waist circumference, in aerobically active individuals with type 1 diabetes.

Diabetes-related antibody-testing is a valuable screening tool for identifying monogenic diabetes - A survey from the worldwide SWEET registry.

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. TRIAL REGISTRATION: NCT04427189.

Corneal nerve and nerve conduction abnormalities in children with type 1 diabetes.

OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Updated reference intervals for urine normetanephrine have no effect on test sensitivity but fewer false positives.

OBJECTIVE: We previously highlighted the problem of frequent false positives in 24 h 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 h 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.

An undergraduate medical curriculum framework for providing care to transgender and gender diverse patients: A modified Delphi study.

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.

Transgender Youth Referred to Clinics for Gender-Affirming Medical Care in Canada.

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 <16 years with gender dysphoria, referred for hormonal suppression or hormone therapy, and 160 linked parent-participants. Measures assessed health, demographics, and visit outcome. 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.

Increasing plasma glucose before the development of type 1 diabetes-the TRIGR study.

OBJECTIVE: The ß-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.

Corneal Confocal Microscopy Predicts the Development of Diabetic Neuropathy: A Longitudinal Diagnostic Multinational Consortium Study.

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.

CYP24A1 and SLC34A1 Pathogenic Variants Are Uncommon in a Canadian Cohort of Children with Hypercalcemia or Hypercalciuria.

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.

Diabetic ketoacidosis at presentation of type 1 diabetes in children in Canada during the COVID-19 pandemic.

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<0.0001) and presentation in severe DKA from 37.0% to 48.3% (P=0.044). These findings are concerning and emphasize the importance of awareness of the signs and symptoms of diabetes. In addition, these findings raise concern about access to appropriate and timely care during the COVID-19 pandemic.

Frequency of Autoantibody-Negative Type 1 Diabetes in Children, Adolescents, and Young Adults During the First Wave of the COVID-19 Pandemic in Germany.

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 ß-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; P upper 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.

Diabetic ketoacidosis at type 1 diabetes diagnosis in children during the COVID-19 pandemic.

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 < 0.001) and incidence of severe DKA was also higher (27.1% in 2020 vs 13.2% in 2019; p = 0.01). CONCLUSIONS: There was a significant increase in DKA and severe DKA in children presenting with new onset DM1 during the COVID-19 pandemic period. This emphasizes the need for educating health care professionals and families to be aware of the symptoms of hyperglycemia and the importance of early diagnosis and treatment even during public health measures for COVID-19.

Previous diabetic ketoacidosis as a risk factor for recurrence in a large prospective contemporary pediatric cohort: Results from the DPV initiative.

OBJECTIVE: To assess the role of previous episodes of diabetic ketoacidosis (DKA) and their time-lag as risk factors for recurring DKA in youth with type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: In a population-based analysis, data from 29,325 children and adolescents with T1D and at least 5 years of continuous follow-up were retrieved from the "Diabetes Prospective Follow-up" (DPV) multi-center registry in March 2020. Statistical analyses included unadjusted comparisons, logistic and negative binomial regression models. RESULTS: Among 29,325 patients with T1D, 86.0% (n = 25,219) reported no DKA, 9.7% (n = 2,833) one, and 4.3% (n = 1,273) more than one episode, corresponding to a DKA rate of 4.4 [95% CI: 4.3-4.6] per 100 patient-years. Female sex, migratory background, higher HbA1c values, higher daily insulin doses, a lower glucose monitoring frequency, and less CGM usage were associated with DKA. In patients with a previous episode, the DKA rate in the most recent year was significantly higher than in patients with no DKA (17.6 [15.9-19.5] vs. 2.8 [2.7-3.1] per 100 patient-years; p < 0.001). Multiple DKAs further increased the recurrence rate. The risk for DKA in the most recent year was higher in patients with an episode in the preceding year than in patients with no previous DKA (OR: 10.0 [95% CI: 8.6-11.8]), and remained significantly elevated 4 years after an episode (OR: 2.3 [1.6-3.1]; p < 0.001). CONCLUSIONS: Each episode of DKA is an independent risk factor for recurrence, even 4 years after an event, underlining the importance of a close follow-up after each episode.

Improved transition to adult care in youth with type 1 diabetes: a pragmatic clinical trial.

AIMS/HYPOTHESIS: 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. METHODS: 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. RESULTS: 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 < 0.01). There were no differences in glycaemic control or diabetic ketoacidosis post transfer. CONCLUSIONS/INTERPRETATION: Our 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. TRIAL REGISTRATION: isrctn.org ISRCTN13459962.

Thiamine-Responsive Megaloblastic Anemia-Related Diabetes: Long-Term Clinical Outcomes in 23 Pediatric Patients From the DPV and SWEET Registries.

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.

Revision of Alberta's Provincial Insulin Pump Therapy Criteria for Adults and Children With Type 1 Diabetes: Process, Rationale and Framework for Evaluation.

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.

Epidemiology of pheochromocytoma and paraganglioma: population-based cohort study.

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.