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Diabetes Care. 2019 Jun 4. pii: dc190102. doi: 10.2337/dc19-0102. [Epub ahead of print]

The Influence of Type 2 Diabetes-Associated Factors on Type 1 Diabetes.

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Baylor College of Medicine, Texas Children's Hospital, Houston, TX
Department of Pediatrics, Indiana University School of Medicine, Indianapolis, IN.
Department of Medicine, Indiana University School of Medicine, Indianapolis, IN.
Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN.
Roudebush VA Medical Center, Indianapolis, IN.
Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, CO.
Departments of Pathology and Pediatrics, University of Florida Diabetes Institute, Gainesville, FL.
University of Miami, Miami, FL.


Current efforts to prevent progression from islet autoimmunity to type 1 diabetes largely focus on immunomodulatory approaches. However, emerging data suggest that the development of diabetes in islet autoantibody-positive individuals may also involve factors such as obesity and genetic variants associated with type 2 diabetes, and the influence of these factors increases with age at diagnosis. Although these factors have been linked with metabolic outcomes, particularly through their impact on β-cell function and insulin sensitivity, growing evidence suggests that they might also interact with the immune system to amplify the autoimmune response. The presence of factors that both forms of diabetes share contributes to disease heterogeneity and thus has important implications. Characteristics that are typically considered to be nonimmune should be incorporated into predictive algorithms that seek to identify at-risk individuals and into the designs of trials for disease prevention. It also poses a challenge in diagnostic classification. Finally, after clinically diagnosing type 1 diabetes, addressing nonimmune elements may help to prevent further deterioration of β-cell function and thus improve clinical outcomes. This Perspectives in Care article highlights the role of type 2 diabetes-associated genetic factors (e.g., gene variants at transcription factor 7-like 2 [TCF7L2]) and obesity (via insulin resistance, inflammation, β-cell stress, or all three) in the pathogenesis of type 1 diabetes and their impacts on age at diagnosis. Recognizing that type 1 diabetes might result from the sum of effects from islet autoimmunity and type 2 diabetes-associated factors, their interactions, or both affects disease prediction, prevention, diagnosis, and treatment.


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