Development of a cardiomyopathy in a model of noninsulin-dependent diabetes

Wistar rats were injected with streptozotocin (SZ) at 3 days of age. This maneuver produced a marked glucose intolerance, as determined by intraperitoneal glucose tolerance tests, but plasma fasting and nonfasting glucose values remained at or near normal throughout the 12-mo study period. Hearts obtained from these glucose-intolerant rats exhibited a progressive cardiomyopathy that consisted of both contractile and metabolic abnormalities. Contractile abnormalities were characterized by reductions in aortic output, ventricular pressure, and cardiac work. Associated with these mechanical defects was a decrease in glucose utilization. These abnormalities were not ameliorated by acute exposure to insulin or changes in the work load of the heart. These results demonstrate that, in the rat, a progressive cardiomyopathy results from persistent glucose intolerance in the absence of fasting hyperglycemia. This cardiomyopathy is reminiscent of that described in human noninsulin-dependent diabetes.