Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross- sectional, genetically stratified survival analysis from UK Biobank

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Frequency and phenotype of type 1 diabetes in the first six decades of life: a cross- sectional, genetically stratified survival analysis from UK Biobank Nicholas J Thomas, MRCP, Samuel E Jones, PhD, Michael N Weedon, PhD, Beverley M Shields, PhD, Richard A Oram, PhD, Prof Andrew T Hattersley, DM The Lancet Diabetes & Endocrinology Volume 6, Issue 2, Pages 122-129 (February 2018) DOI: 10.1016/S2213-8587(17)30362-5 Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY 4.0 license Terms and Conditions

Figure 1 Use of a type 1 diabetes genetic risk score to establish the proportion of population with genetically defined type 1 diabetes (A) Distribution of type 1 genetic risk score in the Wellcome Trust Case Control Consortium type 1 diabetes and type 2 diabetes cohorts.23 Type 1 diabetes is restricted to high type 1 diabetes genetic risk scores. Numbers of individuals with type 2 diabetes above and below the 50th centile (dotted line; fifth centile for type 1 diabetes) will be the same; thus, any excess in the top 50% will be cases of type 1 diabetes. In a population where the proportions of type 1 diabetes and type 2 diabetes are unknown, this method can be used to determine the proportion of type 1 diabetes cases. (B) Schematic showing that the high type 1 diabetes genetic risk group will have the same amount of type 2 diabetes as the low type 1 diabetes genetic risk group in addition to an excess of diabetes contributed by type 1 diabetes. The Lancet Diabetes & Endocrinology 2018 6, 122-129DOI: (10.1016/S2213-8587(17)30362-5) Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY 4.0 license Terms and Conditions

Figure 2 Kaplan-Meier curve of diabetes-free survival in the high and low genetic susceptibility groups Graph shows that diabetes was more likely in the high genetic susceptibility group. HR=hazard ratio. The Lancet Diabetes & Endocrinology 2018 6, 122-129DOI: (10.1016/S2213-8587(17)30362-5) Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY 4.0 license Terms and Conditions

Figure 3 Cumulative excess of genetically defined cases of type 1 diabetes occurring throughout the first six decades of life 58% (749/1286) of type 1 diabetes cases were diagnosed when individuals were aged 30 years or younger; 42% (537/1286) were diagnosed when individuals were aged 31–60 years. The Lancet Diabetes & Endocrinology 2018 6, 122-129DOI: (10.1016/S2213-8587(17)30362-5) Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY 4.0 license Terms and Conditions

Figure 4 Incidence of genetically defined type 1 and type 2 diabetes in the first six decades of life Cases of type 1 diabetes were distributed across all ages of diagnosis, whereas cases of type 2 diabetes increased substantially with increasing age. The Lancet Diabetes & Endocrinology 2018 6, 122-129DOI: (10.1016/S2213-8587(17)30362-5) Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY 4.0 license Terms and Conditions