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We employed machine learning techniques to investigate to what extent data from longitudinal, nationwide Danish health registers can be used to predict individuals at high risk of developing type 2 diabetes (T2D) comorbidities. Leveraging logistic regression-, random forest- and gradient boosting models and register data spanning hospitalizations, drug prescriptions and contacts with primary care contractors from &gt;200,000 individuals newly diagnosed with T2D, we predicted five-year risk of heart failure (HF), myocardial infarction (MI), stroke (ST), cardiovascular disease (CVD) and chronic kidney disease (CKD). For HF, MI, CVD, and CKD, register-based models outperformed a reference model leveraging canonical individual characteristics by achieving area under the receiver operating characteristic curve improvements of 0.06, 0.03, 0.04, and 0.07, respectively. The top 1,000 patients predicted to be at highest risk exhibited observed incidence ratios exceeding 4.99, 3.52, 1.97 and 4.71 respectively. In summary, prediction of T2D comorbidities utilizing Danish registers led to consistent albeit modest performance improvements over reference models, suggesting that register data could be leveraged to systematically identify individuals at risk of developing disease comorbidities.<\/jats:p>","DOI":"10.1038\/s41598-020-58601-7","type":"journal-article","created":{"date-parts":[[2020,2,4]],"date-time":"2020-02-04T06:02:47Z","timestamp":1580796167000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Nationwide prediction of type 2 diabetes comorbidities"],"prefix":"10.1038","volume":"10","author":[{"given":"Piotr","family":"Dworzynski","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Aasbrenn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaus","family":"Rostgaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8264-6785","authenticated-orcid":false,"given":"Mads","family":"Melbye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Alexander","family":"Gerds","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Hjalgrim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tune H.","family":"Pers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,2,4]]},"reference":[{"key":"58601_CR1","unstructured":"World Health Organization. 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