The exhumation of Danish astronomer Tycho Brahe (1546-1601) was performed in 2010 to verify speculative views on the cause of his death. Previous analyses of skeletal and hair remains recovered from his grave refuted the presumption that he died from poisoning. These studies also outlined the possibility that he actually died from an acute illness, echoing the rather vague and inaccurate testimony of some historical records. We performed a detailed paleopathological analysis of Tycho Brahe's skeletal remains, along with a reconstruction of his diet based on carbon and nitrogen stable isotopes analysis and an estimate of his physical status (relative body fat) based on medullar and cortical dimensions of the femoral shaft. The astronomer's remains exhibit bone changes indicative of diffuse idiopathic skeletal hyperostosis (DISH). The study further allows us to classify him as obese (100% reliability according to our decision tree designed from Danish males), and points out his rich diet (high input of animal protein and/or marine resources) and high social status. Comorbidities of DISH and obesity are reviewed, and their influence on health status is discussed. We further consider some conditions associated with metabolic syndrome as possible causes of Tycho Brahe's final symptoms (urinary retention, renal failure and coma), including diabetes, alcoholic ketoacidosis and benign prostatic hypertrophy. Although a definite and specific diagnosis cannot be established, our study points to today's civilization diseases often associated with DISH and metabolic syndrome as the possible cause of death of Tycho Brahe.