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. 2018 May 16;67(7):1216–1225. doi: 10.2337/db18-0065

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© 2018 by the American Diabetes Association.

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.

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Schematic of heterogeneity in clinical presentation and disease course. Left: Theoretical 3D landscape depicting the risk of type 1 diabetes in an individual (vertical dimension) driven by the complex relationships between both known and unknown factors, including genetics, immunity, and metabolic and β-cell parameters (horizontal dimensions). Right: Individual risk landscapes are modified by sources of variation such as age and BMI. Each individual’s risk continues to vary due to environmental exposures and the passage of time, increasing the overall heterogeneity of subject cohorts.