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The earliest change that occurs in the diabetic heart is reduced glucose consumption, with a switch to utilization of fatty acids (FA) predominantly as an energy resource. Although this adaptation might be beneficial in the short-term, over a protracted duration, it is potentially catastrophic given the malicious effects produced by high FA in cardiomyocytes. In this review, we describe how the endothelial cell (EC), a “first-responder” to hyperglycemia, communicates with the underlying cardiomyocyte. As this cross-talk is expected to facilitate increased FA delivery to, and utilization by, the cardiomyocyte, understanding this conversationshould assist in devising new therapeutic strategies to prevent or delay diabetic heart disease.