Publications by authors named "Danièle Pacaud"

69 Publications

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

Horm Res Paediatr 2021 Jul 28:1-9. Epub 2021 Jul 28.

Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Manitoba, Canada.

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.
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http://dx.doi.org/10.1159/000517548DOI Listing
July 2021

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

Diabetes Care 2021 Jul 1. Epub 2021 Jul 1.

University of Manchester, Manchester, U.K.

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/mm was associated with 67% sensitivity, 71% specificity, and a hazard ratio of 2.95 (95% CI 1.70-5.11; < 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.
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http://dx.doi.org/10.2337/dc21-0476DOI Listing
July 2021

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

Paediatr Child Health 2021 Jul 8;26(4):208-209. Epub 2021 Apr 8.

Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.

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.
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http://dx.doi.org/10.1093/pch/pxab017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8083512PMC
July 2021

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

Diabetes Care 2021 May 14. Epub 2021 May 14.

German Center for Diabetes Research (DZD) , Munich-Neuherberg, 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 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; = 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.
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http://dx.doi.org/10.2337/dc20-2791DOI Listing
May 2021

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

Pediatr Diabetes 2021 06 27;22(4):552-557. Epub 2021 Mar 27.

Division of Pediatric Endocrinology, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.

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.
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http://dx.doi.org/10.1111/pedi.13205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8251027PMC
June 2021

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

Pediatr Diabetes 2021 May 21;22(3):455-462. Epub 2021 Feb 21.

Institute of Epidemiology and Medical Biometry, ZIBMT, Ulm University, Ulm, Germany.

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.
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http://dx.doi.org/10.1111/pedi.13185DOI Listing
May 2021

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

Diabetologia 2021 Apr 13;64(4):758-766. Epub 2021 Jan 13.

Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.

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, HbA 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.
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http://dx.doi.org/10.1007/s00125-020-05368-1DOI Listing
April 2021

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

Can J Diabetes 2020 Nov 23. Epub 2020 Nov 23.

Department of Pediatrics, Alberta Children's Hospital, University of Calgary, Calgary, Alberta, Canada.

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.
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http://dx.doi.org/10.1016/j.jcjd.2020.11.006DOI Listing
November 2020

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

Eur J Endocrinol 2021 Jan;184(1):19-28

Division of Endocrinology and Metabolism, Department of Medicine, University of Calgary, Calgary, Alberta, Canada.

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.
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http://dx.doi.org/10.1530/EJE-20-0628DOI Listing
January 2021

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

Can J Diabetes 2021 Apr 18;45(3):228-235.e4. Epub 2020 Aug 18.

Division of Endocrinology and Metabolism, University of Alberta, Edmonton, Alberta, Canada. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jcjd.2020.08.097DOI Listing
April 2021

Association between family history, early growth and the risk of beta cell autoimmunity in children at risk for type 1 diabetes.

Diabetologia 2021 Jan 7;64(1):119-128. Epub 2020 Oct 7.

Pediatric Research Center, Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.

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 group n = 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 (z score/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.

Trial Registration: ClinicalTrials.gov NCT00179777 Graphical abstract.
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http://dx.doi.org/10.1007/s00125-020-05287-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7716821PMC
January 2021

Type 1 Diabetes Mellitus Virtual Patient Network as a Peer Support Community: Protocol for Social Network Analysis and Content Analysis.

JMIR Res Protoc 2020 Aug 31;9(8):e18714. Epub 2020 Aug 31.

Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.

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.
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http://dx.doi.org/10.2196/18714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490683PMC
August 2020

Youth with diabetes and their parents' perspectives on transition care from pediatric to adult diabetes care services: A qualitative study.

Health Sci Rep 2020 Sep 6;3(3):e181. Epub 2020 Aug 6.

Division of Pediatric Endocrinology and Diabetes, Department of Pediatrics, Cumming School of Medicine University of Calgary Calgary Alberta Canada.

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.
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http://dx.doi.org/10.1002/hsr2.181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7410016PMC
September 2020

Rapid Corneal Nerve Fiber Loss: A Marker of Diabetic Neuropathy Onset and Progression.

Diabetes Care 2020 08 5;43(8):1829-1835. Epub 2020 Mar 5.

Division of Endocrinology, Leadership Sinai Centre for Diabetes, University of Toronto, Toronto, Canada

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%], = 0.31). RNCFL was more common in those with baseline DSP (47% vs. 30% in those without baseline DSP, = 0.001), which was associated with lower peroneal conduction velocity but not with baseline HbA 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.
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http://dx.doi.org/10.2337/dc19-0951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7372054PMC
August 2020

Pragmatic trial evaluating the effectiveness of a patient navigator to decrease emergency room utilisation in transition age youth with chronic conditions: the Transition Navigator Trial protocol.

BMJ Open 2019 12 10;9(12):e034309. Epub 2019 Dec 10.

Division of Cardiology, Department of Pediatrics, University of Alberta, Edmonton, Alberta, Canada.

Introduction: Transition 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 Analysis: Pragmatic 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 Dissemination: Ethics 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 Number: NCT03342495.
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http://dx.doi.org/10.1136/bmjopen-2019-034309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924868PMC
December 2019

Exploring Knowledge and Safety Practices for Driving in Youth With Type 1 Diabetes.

Can J Diabetes 2020 Mar 10;44(2):169-174.e2. Epub 2019 Jun 10.

Department of Pediatrics, Alberta Children's Hospital, Calgary, Alberta, Canada; Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada. Electronic address:

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.
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http://dx.doi.org/10.1016/j.jcjd.2019.06.001DOI Listing
March 2020

Early corneal nerve fibre damage and increased Langerhans cell density in children with type 1 diabetes mellitus.

Sci Rep 2019 06 19;9(1):8758. Epub 2019 Jun 19.

University of Calgary, Calgary, AB, Canada.

Corneal confocal microscopy (CCM) has been used to identify corneal nerve damage and increased Langerhans cell (LC) density in adults with Type 1 diabetes mellitus (T1DM). The purpose of this study was to evaluate whether corneal confocal microscopy can identify early corneal nerve damage and change in LC density in children and adolescents with T1DM. 64 participants with T1DM (age-14.6 ± 2.5 years, duration of diabetes-9.1 ± 2.7 years, HbA1c-75.66 ± 2.53 mmol/mol [9.1 ± 1.8%]) and 48 age-matched healthy control subjects underwent CCM. Sub-basal corneal nerve morphology and the density of mature and immature LCs was quantified. Corneal nerve fibre length and branch density were lower, whilst fibre density and tortuosity did not differ and both immature and mature LC density was significantly higher in T1DM compared to control subjects. There was no association between HbA1c and duration of diabetes with nerve fibre parameters or LC's density. Children and adolescents with T1DM demonstrate early immune activation and nerve degeneration.
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http://dx.doi.org/10.1038/s41598-019-45116-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6584636PMC
June 2019

Health care stakeholder perspectives regarding the role of a patient navigator during transition to adult care.

BMC Health Serv Res 2019 Jun 17;19(1):390. Epub 2019 Jun 17.

Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada.

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.
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http://dx.doi.org/10.1186/s12913-019-4227-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6580652PMC
June 2019

Knowledge and practice of harm-reduction behaviours for alcohol and other illicit substance use in adolescents with type 1 diabetes.

Paediatr Child Health 2019 Feb 7;24(1):e51-e56. Epub 2018 Jun 7.

Department of Pediatrics, Alberta Children's Hospital, Calgary, Alberta.

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.
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http://dx.doi.org/10.1093/pch/pxy075DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376295PMC
February 2019

The influence of treatment, age at onset, and metabolic control on height in children and adolescents with type 1 diabetes-A SWEET collaborative study.

Pediatr Diabetes 2018 12 10;19(8):1441-1450. Epub 2018 Oct 10.

DECCP, Pediatric Clinic/CHL, Luxembourg, Luxembourg Centre Hospitalier de Luxembourg, Luxembourg, Luxembourg.

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 (<2 years: 0.36 [±0.06]; 2-<5 years: 0.34 [±0.06]; ≥5 years: 0.21 [±0.06]) and if they were pump users: 0.35 ± 0.05 vs 0.25 ± 0.05 (>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.
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http://dx.doi.org/10.1111/pedi.12751DOI Listing
December 2018

Prevalence of underweight, overweight, and obesity in children and adolescents with type 1 diabetes: Data from the international SWEET registry.

Pediatr Diabetes 2018 11 22;19(7):1211-1220. Epub 2018 Aug 22.

Pediatric Diabetes and Metabolic Disorders Unit, University of Verona, University City Hospital, Verona, Italy.

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), OW (+1SD < BMI-SDS ≤ +2SD), and obese (OB) (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 < 0.0001). In males, BMI-SDS significantly decreased by age (P < 0.0001) in the first three age categories 0.61 ± 0.06 (2 to <10 years), 0.47 ± 0.06 (10 to <13 years), 0.34 ± 0.05 (13 to <16 years). In females, BMI-SDS showed a U-shaped distribution by age (P < 0.0001): 0.54 ± 0.04 (2 to <10 years), 0.39 ± 0.04 (10 to <13 years), 0.55 ± 0.04 (13 to <16 years). BMI-SDS increased by diabetes duration (<2 years: 0.38 ± 0.05, 2 to <5 years: 0.44 ± 0.05, and ≥5 years: 0.50 ± 0.05, P < 0.0001). Treatment modality did not affect BMI-SDS. Adjusted HbA1c was significantly higher in females than in males (8.20% ± 0.10% vs 8.06% ± 0.10%, P < 0.0001). In both genders, the association between HbA1c and BMI-SDS was U-shaped with the highest HbA1c in the UW and obesity groups.

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.
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http://dx.doi.org/10.1111/pedi.12730DOI Listing
November 2018

Corneal confocal microscopy for identification of diabetic sensorimotor polyneuropathy: a pooled multinational consortium study.

Diabetologia 2018 08 4;61(8):1856-1861. Epub 2018 Jun 4.

Centre for Endocrinology and Diabetes, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.

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 < 0.001) and 0.68 in type 2 diabetes (p < 0.001) and was approximately reproduced in validation sets. The optimal threshold for automated CNFL was 12.5 mm/mm in type 1 diabetes and 12.3 mm/mm in type 2 diabetes. In the total cohort, a lower threshold value below 8.6 mm/mm to rule in DSP and an upper value of 15.3 mm/mm to rule out DSP were associated with 88% specificity and 88% sensitivity.

Conclusions/interpretation: We established the diagnostic validity and common diagnostic thresholds for CNFL in type 1 and type 2 diabetes. Further research must determine to what extent CNFL can be deployed in clinical practice and in clinical trials assessing the efficacy of disease-modifying therapies for DSP.
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http://dx.doi.org/10.1007/s00125-018-4653-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061173PMC
August 2018

Prevalence of alcohol, tobacco, cannabis and other illicit substance use in a population of Canadian adolescents with type 1 diabetes compared to a general adolescent population.

Paediatr Child Health 2018 May 23;23(3):185-190. Epub 2017 Nov 23.

Department of Pediatrics, Alberta Children's Hospital, Calgary, Alberta.

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<0.0001).

Conclusions: Proportions reporting having ever consumed alcohol, tobacco or cannabis were not significantly different between the two groups. However, the proportion of adolescents with T1DM who reported ever consuming an illicit substance was different from the comparison group. It is important to explore risky behaviours with adolescents with T1DM and focus on prevention and education during routine clinic visits.
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http://dx.doi.org/10.1093/pch/pxx157DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951101PMC
May 2018

Stigma and Its Association With Glycemic Control and Hypoglycemia in Adolescents and Young Adults With Type 1 Diabetes: Cross-Sectional Study.

J Med Internet Res 2018 04 20;20(4):e151. Epub 2018 Apr 20.

Centre for Outcomes Research and Evaluation, Research Institute of the McGill University Health Centre, Department of Medicine, McGill University, Montreal, QC, Canada.

Background: Qualitative studies in type 1 diabetes indicate that visibility of diabetes supplies, self-care, and hypoglycemia symptoms are associated with stigma and suboptimal management. This may be particularly salient in youth who face concurrent challenges such as establishing autonomy and making vocational choices.

Objective: The aim of the study was to estimate stigma prevalence in youth (aged 14-24 years) with type 1 diabetes and its associations with glycemic control.

Methods: Participants, recruited largely through social media, were asked to complete a Web-based survey and to send via mail capillary blood samples for glycated hemoglobin (HbA) measurement. The primary definition of stigma required endorsement of one or more of 3 stigma-specific items of the Barriers to Diabetes Adherence questionnaire. These addressed avoidance of diabetes management with friends present, difficulty telling others about diabetes diagnosis, and embarrassment in performing diabetes care with others present. Poor glycemic control was defined as HbA>9% (ie, >75 mmol/mol; measured value when available, else self-report) and/or ≥1 severe hypoglycemic episode in the previous year (reported requiring assistance from someone else during the episode). Stigma prevalence was computed (95% CI), and associations with glycemic control were evaluated (multivariate logistic regression models).

Results: Among the 380 respondents, stigma prevalence was 65.5% (95% CI 60.7-70.3). Stigma was associated with a 2-fold higher odds of poor glycemic control overall (odds ratio [OR] 2.25, 95% CI 1.33-3.80; adjusted for age, sex, and type of treatment). There were specific associations with both HbA>9% (75 mmol/mol; OR 3.05, 95% CI 1.36-6.86) and severe hypoglycemia in the previous year (OR 1.86, 95% CI 1.05-3.31).

Conclusions: There is a high prevalence of stigma in youth with type 1 diabetes that is associated with both elevated HbA levels and severe hypoglycemia. Targeted strategies to address stigma are needed.

Trial Registration: ClinicalTrials.gov NCT02796248; http://clinicaltrials.gov/ct2/show/NCT02796248 (Archived by WebCite at http://www.webcitation.org/6yisxeV0B).
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http://dx.doi.org/10.2196/jmir.9432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5935805PMC
April 2018

Evaluation of a Diabetes Coach Program Aimed to Improve the Care of Children and Youth With Type 1 Diabetes and With Compromised Control.

Can J Diabetes 2018 Oct 31;42(5):540-544. Epub 2018 Jan 31.

Section of Pediatric Endocrinology, Department of Pediatrics, Alberta Children's Hospital, Calgary, Alberta, Canada; University of Calgary, Calgary, Alberta, Canada; Alberta Children's Hospital Research Institute, Calgary, Alberta, Canada.

Objective: To evaluate the impact of the Diabetes Coach Program (DCP) on glycated hemoglobin (A1C) levels in youth with type 1 diabetes. The youth were referred to and participated in the DCP between October 2011 and May 2016.

Methods: The Diabetes Coach visited families in their homes every 1 to 2 weeks and updated patients' diabetes teams regularly. A1C levels before the DCP were compared with A1C levels during and after discharge from the DCP. Six participating families completed satisfaction surveys via telephone.

Results: The DCP included 23 participants (43% male; median age, 11 years; range, 8.8 to 14.5 years); median duration of type 1 diabetes, 1.7 years (range, 0.1 to 6.3 years); median time in the DCP, 1.5 years (range, 0.2 to 2.5 years). During involvement in the program, median A1C levels decreased from baselines of 11.1% (range, 8.9% to 15.3%) to 10.2% (range, 7.6% to 12.4%) (p=0.0028). For 11 of 13 patients discharged from the DCP, the most recent median A1C levels, 11.2% (range, 9.1% to 13.6%), an average of 2.4 years later, were not different from the initial A1C levels (p=0.85). Family feedback was overwhelmingly positive.

Conclusions: Participation in the DCP decreased A1C values in pediatric patients; however, the levels were not sustained after visits stopped. Pediatric health coaches may play an important role in the management of type 1 diabetes, but further research is needed to explore their benefits and how positive effects can be sustained.
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http://dx.doi.org/10.1016/j.jcjd.2018.01.005DOI Listing
October 2018

Congenital adrenal hyperplasia causing hypertension: an illustrative review.

J Hum Hypertens 2018 02 18;32(2):150-157. Epub 2017 Dec 18.

University of Calgary, Calgary, AB, Canada.

Congenital adrenal hyperplasia (CAH) is often considered a pediatric endocrinology condition, but we present two cases of young adults who presented with hypertension. An 18-year-old woman was found to have hypertension and hypokalemia when she presented for gonadectomy for 46, XY gonadal dysgenesis. She was subsequently found to have low cortisol, elevated progesterone, and elevated aldosterone. Genetic testing confirmed 17-alpha hydroxylase deficiency (17OHD). Her case was unique in that 17OHD usually presents with hypoaldosteronism. We also present the case of a 15-year-old man (46, XX) with resistant hypertension due to 11-beta hydroxylase deficiency (11OHD) who underwent bilateral adrenalectomy for control of hypertension. The relevant literature is reviewed including the pathophysiology, clinical presentation, and treatment of the hypertensive variants of congenital adrenal hyperplasia. We also review the unique areas of hyperaldosteronism in 17OHD and the use of bilateral adrenalectomy for control of hypertension in CAH.
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http://dx.doi.org/10.1038/s41371-017-0002-5DOI Listing
February 2018

Is the Correlation between Salivary Cortisol and Serum Cortisol Reliable Enough to Enable Use of Salivary Cortisol Levels in Preterm Infants?

Am J Perinatol 2017 11 15;34(13):1302-1305. Epub 2017 May 15.

Section of Pediatric Endocrinology, Department of Pediatrics, University of Calgary, Calgary, Alberta, Canada.

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http://dx.doi.org/10.1055/s-0037-1603345DOI Listing
November 2017

Clinical, genetic, and structural basis of congenital adrenal hyperplasia due to 11β-hydroxylase deficiency.

Proc Natl Acad Sci U S A 2017 03 22;114(10):E1933-E1940. Epub 2017 Feb 22.

Childrens Hospital, University of Munich, 80539 Munich, Germany.

Congenital adrenal hyperplasia (CAH), resulting from mutations in , a gene encoding 11β-hydroxylase, represents a rare autosomal recessive Mendelian disorder of aberrant sex steroid production. Unlike CAH caused by 21-hydroxylase deficiency, the disease is far more common in the Middle East and North Africa, where consanguinity is common often resulting in identical mutations. Clinically, affected female newborns are profoundly virilized (Prader score of 4/5), and both genders display significantly advanced bone ages and are oftentimes hypertensive. We find that 11-deoxycortisol, not frequently measured, is the most robust biochemical marker for diagnosing 11β-hydroxylase deficiency. Finally, computational modeling of 25 missense mutations of revealed that specific modifications in the heme-binding (R374W and R448C) or substrate-binding (W116C) site of 11β-hydroxylase, or alterations in its stability (L299P and G267S), may predict severe disease. Thus, we report clinical, genetic, hormonal, and structural effects of gene mutations in the largest international cohort of 108 patients with steroid 11β-hydroxylase deficiency CAH.
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http://dx.doi.org/10.1073/pnas.1621082114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5347606PMC
March 2017
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