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

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.Peer reviewe

The relationship between physical activity level and cardiovascular disease biomarkers in healthy, normal-weight 3-to 6-year-old children and their parents

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 modeling 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 spend in light physical activity, and between triglyceride and time spent in sedentary behavior, findings to be confirmed in longitudinal prospective studies.The accepted manuscript in pdf format is listed with the files at the bottom of this page. The presentation of the authors' names and (or) special characters in the title of the manuscript may differ slightly between what is listed on this page and what is listed in the pdf file of the accepted manuscript; that in the pdf file of the accepted manuscript is what was submitted by the author

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

Objective: The β-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 \u3c 0.001). An increase in glucose from the previous sample predicted clinical diabetes (p \u3c 0.001) but not autoantibodies. An increase of HbA1c of 20% or 30% from the previous sample predicted the development of any autoantibody (p \u3c 0.003 resp \u3c0.001) and the development of diabetes (p \u3c 0.002 resp \u3c0.001. 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 \u3c 0.001) but higher than those who developed any autoantibody (5.10%, 0.30; 32.21 mmol/mol, 3.49; p \u3c 0.001), or multiple autoantibodies (5.11%, 0.35; 32.26 mmol/mol, 3.92; p \u3c 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

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

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 &amp;lt; 0.001). An increase in glucose from the previous sample predicted clinical diabetes (p &amp;lt; 0.001) but not autoantibodies. An increase of HbA1c of 20% or 30% from the previous sample predicted the development of any autoantibody (p &amp;lt; 0.003 resp &amp;lt; 0.001) and the development of diabetes (p &amp;lt; 0.002 resp &amp;lt; 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 &amp;lt; 0.001) but higher than those who developed any autoantibody (5.10%, 0.30; 32.21 mmol/mol, 3.49; p &amp;lt; 0.001), or multiple autoantibodies (5.11%, 0.35; 32.26 mmol/mol, 3.92; p &amp;lt; 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 &amp; Human ServicesNational Institutes of Health (NIH) - USANIH Eunice Kennedy Shriver National Institute of Child Health &amp; 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</p

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

Abstract 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