Sympathetic Dysfunction in Type 1 Diabetes: Association with Impaired Myocardial Blood Flow Reserve and Diastolic Dysfunction

Objectives: 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.

Background: In diabetes, augmented cardiac sympathetic tone and abnormal MBF regulation may predispose to myocardial injury and enhanced cardiac risk.

Methods: 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). [(11)C]meta-hydroxyephedrine ([(11)C]HED) and positron emission tomography (PET) were used to explore left ventricular (LV) sympathetic integrity and [(13)N]ammonia-PET to assess MBF regulation in response to cold pressor testing (CPT) and adenosine infusion.

Results: Deficits of LV [(11)C]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 approximately 45% (p < 0.05) in DMA+ subjects. Diastolic dysfunction was detected by two-dimensional echocardiography in 5 of 8 and 0 of 8 consecutively tested DMA+ and DC subjects, respectively.

Conclusions: Augmented cardiac sympathetic tone and responsiveness and impaired myocardial perfusion may contribute to myocardial injury in diabetes.