Investigating misclassification of type 1 diabetes in a population-based cohort of British Pakistanis and Bangladeshis using polygenic risk scores
Authors: Liu Timing , Sankareswaran Alagu , Paterson Gordon ,   Genes & Health Research Team, Fraser Diane P , Hodgson Sam , Huang Qin Qin , Heng Teng Hiang , Ladwa Meera , Thomas Nick , van Heel David A. , Weedon Michael N. , Yajnik Chittaranjan S , Oram Richard A , Chandak Giriraj R , Martin Hilary C , Finer Sarah 
Published: August 2023

AbstractAimsCorrect classification of type 1 (T1D) and type 2 diabetes (T2D) is challenging due to overlapping clinical features and the increasingly early onset of T2D, particularly in South Asians. We used polygenic risk scores (PRSs) in a British Bangladeshi and Pakistani population with diabetes to estimate the proportion and misclassification rate of T1D in insulin-treated individuals with ambiguous features.MethodsUsing linked health records from the Genes & Health cohort (n=38,344) we defined four groups: 31 T1D cases, 1,842 T2D cases, and after excluding these, 839 insulin-treated individuals with ambiguous features and 5,174 controls. Combining these with 307 confirmed T1D cases and 307 controls from India, we calculated ancestry-corrected PRSs for T1D and T2D, with which we estimated the proportion of T1D cases within the ambiguous group and evaluated misclassification.ResultsWe estimated that the prevalence of T1D was ∼6% within the ambiguous group, or ∼4.5% within the subset who had T2D codes in their health records. We saw no significant association between the T1D or T2D PRS and BMI at diagnosis, time to insulin, or the presence of T1D or T2D diagnostic codes amongst the T2D or ambiguous cases, suggesting that these clinical features are not particularly helpful at aiding diagnosis in ambiguous cases.ConclusionsWe estimate that about one in twenty of British Pakistanis and Bangladeshis with diabetes who are treated with insulin and have ambiguous clinical features have been classified incorrectly in their health records, and in fact have T1D. This emphasises that robust identification of T1D cases and appropriate clinical care may require routine measurement of diabetes autoantibodies and C-peptide.Research in contextWhat is already known about this subject?- Correct classification of type 1 (T1D) and type 2 diabetes (T2D) is challenging due to overlapping clinical features and the increasingly early onset of T2D, particularly in people of South Asian descent.- Polygenic risk scores (PRSs) are useful tools to aid the classification of people with diabetes.What is the key question?- What proportion of insulin-treated diabetic individuals with ambiguous clinical features have been clinically misclassified and in fact have T1D, amongst a cohort of British Pakistani and Bangladeshi adults?What are the new findings?- Based on analyses of polygenic risk scores, the prevalence of T1D was found to be ∼6% within patients who were insulin-treated but with ambiguous features, and ∼4.5% were estimated to have been misclassified.- Clinical features such as BMI at diagnosis, time to insulin, or presence of T1D/T2D codes were not significantly associated with T1D or T2D PRS.How might this impact on clinical practice in the foreseeable future?- These findings emphasise the importance of routine collection of diabetes autoantibodies and C-peptide measurements to identify T1D cases robustly, especially in countries where diabetes cases are diagnosed in primary care without input from diabetologists.