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.