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Throughout most of its history, diabetes mellitus was considered, classified and promulgated as a disease of the kidneys. Recognized early in Antiquity by its excessive urine output, its clinical features and fatal outcome were recorded by the end of the first century A.D. by Areteus of Cappadocia and attributed to a weakness of the retentive ability of the kidneys by Galen. The saccharine character of the urine recognized from the sweetness of its taste in 1674 and that of the blood in 1774, was identified as due to glucose in 1815. Refinements in the measurement of glucose ascribed diabetes to increased blood sugar and early attempts at its dietary therapy, but the appearance of sugar in the urine continued to be attributed to the decreased retentive properties of the kidneys well into the middle of the 19th century. The experimental production of diabetes in pancreatectomized dogs in 1889, and ultimately the isolation of insulin in 1922, clearly established diabetes as an endocrine disease due to insulin deficiency that could be controlled by replacement therapy. The history of diabetes as a disease of the kidneys was now over. That of diabetes as a cause of kidney disease was launched shortly thereafter, in 1936.