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Understanding and preventing type 1 diabetes through the unique working model of TrialNet.

ABSTRACT: Type 1 diabetes is an autoimmune disease arising from the destruction of pancreatic insulin-producing beta cells. The disease represents a continuum, progressing sequentially at variable rates through identifiable stages prior to the onset of symptoms, through diagnosis and into the critical periods that follow, culminating in a variable depth of beta cell depletion. The ability to identify the very earliest of these presymptomatic stages has provided a setting in which prevention strategies can be trialled, as well as furnishing an unprecedented opportunity to study disease evolution, including intrinsic and extrinsic initiators and drivers. This niche opportunity is occupied by Type 1 Diabetes TrialNet, an international consortium of clinical trial centres that leads the field in intervention and prevention studies, accompanied by deep longitudinal bio-sampling. In this review, we focus on discoveries arising from this unique bioresource, comprising more than 70,000 samples, and outline the processes and science that have led to new biomarkers and mechanistic insights, as well as identifying new challenges and opportunities. We conclude that via integration of clinical trials and mechanistic studies, drawing in clinicians and scientists and developing partnership with industry, TrialNet embodies an enviable and unique working model for understanding a disease that to date has no cure and for designing new therapeutic approaches.

SUBMITTER: Battaglia M

PROVIDER: S-EPMC5838353 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature

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Understanding and preventing type 1 diabetes through the unique working model of TrialNet.

Battaglia Manuela M Anderson Mark S MS Buckner Jane H JH Geyer Susan M SM Gottlieb Peter A PA Kay Thomas W H TWH Lernmark Åke Å Muller Sarah S Pugliese Alberto A Roep Bart O BO Greenbaum Carla J CJ Peakman Mark M

Diabetologia 20170802 11

Type 1 diabetes is an autoimmune disease arising from the destruction of pancreatic insulin-producing beta cells. The disease represents a continuum, progressing sequentially at variable rates through identifiable stages prior to the onset of symptoms, through diagnosis and into the critical periods that follow, culminating in a variable depth of beta cell depletion. The ability to identify the very earliest of these presymptomatic stages has provided a setting in which prevention strategies can ...[more]

PMID: 28770323

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Project description:Aims/hypothesisMethods to identify individuals at highest risk for type 1 diabetes are essential for the successful implementation of disease-modifying interventions. Simple metabolic measures are needed to help stratify autoantibody-positive (Aab+) individuals who are at risk of developing type 1 diabetes. HOMA2-B is a validated mathematical tool commonly used to estimate beta cell function in type 2 diabetes using fasting glucose and insulin. The utility of HOMA2-B in association with type 1 diabetes progression has not been tested.MethodsBaseline HOMA2-B values from single-Aab+ (n = 2652; mean age, 21.1 ± 14.0 years) and multiple-Aab+ (n = 3794; mean age, 14.5 ± 11.2 years) individuals enrolled in the TrialNet Pathway to Prevention study were compared. Cox proportional hazard models were used to determine associations between HOMA2-B tertiles and time to progression to type 1 diabetes, with adjustments for age, sex, HLA status and BMI z score. Receiver operating characteristic (ROC) analysis was used to test the association of HOMA2-B with type 1 diabetes development in 1, 2, 5 and 10 years.ResultsAt study entry, HOMA2-B values were higher in single- compared with multiple-Aab+ Pathway to Prevention participants (91.1 ± 44.5 vs 83.9 ± 38.9; p < 0.001). Single- and multiple-Aab+ individuals in the lowest HOMA2-B tertile had a higher risk and faster rate of progression to type 1 diabetes. For progression to type 1 diabetes within 1 year, area under the ROC curve (AUC-ROC) was 0.685, 0.666 and 0.680 for all Aab+, single-Aab+ and multiple-Aab+ individuals, respectively. When correlation between HOMA2-B and type 1 diabetes risk was assessed in combination with additional factors known to influence type 1 diabetes progression (insulin sensitivity, age and HLA status), AUC-ROC was highest for the single-Aab+ group's risk of progression at 2 years (AUC-ROC 0.723 [95% CI 0.652, 0.794]).Conclusions/interpretationThese data suggest that HOMA2-B may have utility as a single-time-point measurement to stratify risk of type 1 diabetes development in Aab+ individuals.

Project description:BackgroundDiabetes care is suboptimal in First Nations populations. Innovative and culturally-relevant approaches are needed to promote proactive organization of diabetes care for diabetes patients on-reserve in Canada. The Reorganizing the Approach to Diabetes care through the Application of Registries (RADAR) model is one strategy to improve care: an integrated disease registry and electronic health record for community healthcare workers with centralized care coordination. The aim of this study was to qualitatively assess the organization of type 2 diabetes care in participating communities in Alberta, Canada, at baseline prior to implementing RADAR.MethodsUsing qualitative description, we purposefully sampled healthcare workers involved in diabetes care at each health center. We used the 5Rs framework (i.e., Recognize, Register, Resource, Relay, Recall) to inform the baseline assessment and conducted group interviews in 6 communities with 16 healthcare workers. Detailed notes were taken and validated by participants. Data was managed using ATLAS.ti 8 and analyzed using content analysis.ResultsWe found strong commitment and effort by local healthcare workers to support people living with type 2 diabetes in their communities. However, healthcare workers were limited in their ability to identify (i.e., recognize), track (i.e., register and relay) and manage (i.e., resource and recall) people with type 2 diabetes as proposed by the 5Rs framework. The organization of diabetes care was often reactive and dependent on patients' abilities to navigate the health system. Interestingly, participants talked about the 5Rs in relationship to one another, not in a linear or isolated manner.ConclusionsOverall, the organization of diabetes care in participating communities did not align with the recommended approach of the 5Rs framework. In addition, we propose "reimagining" the 5Rs to reflect the interdependence and mediation of components situated within human and financial resources. This will better equip healthcare workers to assess, plan and execute organized and proactive diabetes care. However, the onus on people living with type 2 diabetes to engage with healthcare services remains a concern.Trial registrationISRCTN.com, ISRCTN14359671.

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Understanding and preventing type 1 diabetes through the unique working model of TrialNet.

Publications

Understanding and preventing type 1 diabetes through the unique working model of TrialNet.

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