Abstract
SummaryBackgroundType 1 diabetes is typically considered a disease of children and young adults. Genetic susceptibility to young-onset type 1 diabetes is well defined and does not predispose to type 2 diabetes. It is not known how frequently genetic susceptibility to type 1 diabetes leads to a diagnosis of diabetes after age 30 years. We aimed to investigate the frequency and phenotype of type 1 diabetes resulting from high genetic susceptibility in the first six decades of life.MethodsIn this cross-sectional analysis, we used a type 1 diabetes genetic risk score based on 29 common variants to identify individuals of white European descent in UK Biobank in the half of the population with high or low genetic susceptibility to type 1 diabetes. We used Kaplan-Meier analysis to evaluate the number of cases of diabetes in both groups in the first six decades of life. We genetically defined type 1 diabetes as the additional cases of diabetes that occurred in the high genetic susceptibility group compared with the low genetic susceptibility group. All remaining cases were defined as type 2 diabetes. We assessed the clinical characteristics of the groups with genetically defined type 1 or type 2 diabetes.Findings13 250 (3·5%) of 379 511 white European individuals in UK Biobank had developed diabetes in the first six decades of life. 1286 more cases of diabetes were in the half of the population with high genetic susceptibility to type 1 diabetes than in the half of the population with low genetic susceptibility. These genetically defined cases of type 1 diabetes were distributed across all ages of diagnosis; 537 (42%) were in individuals diagnosed when aged 31–60 years, representing 4% (537/12 233) of all diabetes cases diagnosed after age 30 years. The clinical characteristics of the group diagnosed with type 1 diabetes when aged 31–60 years were similar to the clinical characteristics of the group diagnosed with type 1 diabetes when aged 30 years or younger. For individuals diagnosed with diabetes when aged 31–60 years, the clinical characteristics of type 1 diabetes differed from those of type 2 diabetes: they had a lower BMI (27·4 kg/m2 [95% CI 26·7–28·0] vs 32·4 kg/m2 [32·2–32·5]; p<0·0001), were more likely to use insulin in the first year after diagnosis (89% [476/537] vs 6% [648/11 696]; p<0·0001), and were more likely to have diabetic ketoacidosis (11% [61/537] vs 0·3% [30/11 696]; p<0·0001).InterpretationGenetic susceptibility to type 1 diabetes results in non-obesity-related, insulin-dependent diabetes, which presents throughout the first six decades of life. Our results highlight the difficulty of identifying type 1 diabetes after age 30 years because of the increasing background prevalence of type 2 diabetes. Failure to diagnose late-onset type 1 diabetes can have serious consequences because these patients rapidly develop insulin dependency.FundingWellcome Trust and Diabetes UK.
Highlights
Type 1 diabetes is caused by autoimmune destruction of pancreatic β cells in genetically predisposed indivi duals and results in severe insulin deficiency with a requirement for treatment with insulin
We have previously shown that, a high type 1 diabetes genetic risk score can occur in people with type 2 diabetes or without diabetes,[16] very few individuals (
We selected 379 511 unrelated individuals of white European descent from the initial UK Biobank dataset of 502 667 individuals with genetic data available. We ranked those individuals by type 1 diabetes genetic risk score and split them around the median score into a high genetic risk score group (n=189 508) and a low genetic risk score group (n=190 003). 13 250 (3·5%) individuals had developed diabetes in the first six decades of life, 7268 of whom had a high type 1 diabetes genetic risk score and 5982 of whom had a low type 1 diabetes genetic risk score
Summary
Type 1 diabetes is caused by autoimmune destruction of pancreatic β cells in genetically predisposed indivi duals and results in severe insulin deficiency with a requirement for treatment with insulin. It is typically considered a disease of childhood and adolescence, but can occur at any age. More than 50% of patients diagnosed with type 1 diabetes after age 35 years were shown to have type 2 diabetes in long-term follow-up.[4,5] many older patients initially believed to have type 2 diabetes because of their age at diagnosis deteriorate rapidly and are subsequently found to have type 1 diabetes.[6] Few studies[2] have investigated how frequently type 1 diabetes presents in later life
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
