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Objective: In view of low prevalence rates, diabetes is discussed as a protective factor for the occurrence of Takotsubo syndrome (TTS). Furthermore, it was associated with improved outcome in a small single-center analysis. Therefore, this study assessed the prevalence and prognostic relevance of concomitant diabetes in TTS.Research Design and Methods: A total of 826 patients with TTS were enrolled in an international, multicenter, registry-based study (eight centers in Italy and Germany). All-cause mortality was compared between patients with diabetes and patients without diabetes, and the independent predictive value of diabetes was evaluated in multivariate regression analysis.Results: The prevalence of diabetes was 21.1% (n = 174). TTS patients with diabetes were older (P < 0.001), were more frequently male (P = 0.003), had a higher prevalence of hypertension (P < 0.001), physical triggers (P = 0.041), and typical apical ballooning (P = 0.010), had a lower left ventricular ejection fraction (P = 0.008), had a higher rate of pulmonary edema (P = 0.032), and had a longer hospital stay (P = 0.009). However, 28-day all-cause mortality did not differ between patients with diabetes and patients without diabetes (6.4% vs. 5.7%; hazard ratio [HR] 1.11 [95% CI 0.55-2.25]; P = 0.772). Longer-term follow-up after a median of 2.5 years revealed a significantly higher mortality among TTS patients with diabetes (31.4% vs. 16.5%; P < 0.001), and multivariate regression analysis identified diabetes as an independent predictor of adverse outcome (HR 1.66 [95% CI 1.16-2.39]; P = 0.006).Conclusions: Diabetes is not uncommon in patients with TTS, is associated with increased longer-term mortality rates, and is an independent predictor of adverse outcome irrespective of additional risk factors. [ABSTRACT FROM AUTHOR]