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The effects of chronic antidiabetic treatment were examined in a clinically manifest, but non-ketotic diabetic animal model in which increased stabilization of steric structure in the cardiac connective tissue and left ventricular diastolic stiffness have been demonstrated. These changes accounted for decreased left ventricular performance during left ventricular afterload. Each of 8 diabetic dogs was given daily 8-16 IU of insulin, 250-750 mg carbutamide or 2-10 mg glibenclamide, respectively; doses were always adjusted to the actual metabolic requirements and findings were compared to those of 11 untreated diabetic and 6 healthy dogs. After three months, the hemodynamic and metabolic studies showed that the metabolically controlled diabetic dogs had less marked alterations in the connective cardiac tissue, left ventricular diastolic stiffness and performance. Apart from a considerable rise of arterial blood pressure during carbutamide treatment, no other difference was found in the cardiac actions of the three hypoglycemic agents tested.