This study was designed to explore the relationships of early diabetic microangiopathy to alterations of cardiac sympathetic tone and myocardial blood flow(MBF)regulation in subjects with stable type 1 diabetes. In diabetes, augmented cardiac sympathetic tone and abnormal MBF regulation may predispose to myocardial injury and enhanced cardiac risk. Subject groups comprised healthy controls(C)(n=10), healthy diabetic subjects(DC)(n=12), and diabetic subjects with very early diabetic microangiopathy(DMA+)(n=16). [ 11C]meta-hydroxyephedrine([11C]HED)and positron emission tomography(PET)were used to explore left ventricular(LV)sympathetic integrity and [13N]ammonia-PET to assess MBF regulation in response to cold pressor testing(CPT)and adenosine infusion. Deficits of LV [ 11C]HED retention were extensive and global in the DMA+subjects(36±31%vs. 1±1%in DC subjects; p< 0.01)despite preserved autonomic reflex tests. On CPT, plasma norepinephrine excursions were two-fold greater than in C and DC subjects(p< 0.05), and basal LV blood flow decreased(-12%, p< 0.05)in DMA+but not in C or DC subjects(+45%and +51%, respectively). On adenosine infusion, compared with C subjects, MBF reserve decreased by-45%(p< 0.05)in DMA+subjects. Diastolic dysfunctionwas detected by two-dimensional echocardiography in 5 of 8 and 0 of 8 consecutively tested DMA+and DC subjects, respectively. Augmented cardiac sympathetic tone and responsiveness and impaired myocardial perfusion may contribute to myocardial injury in diabetes.
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