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). [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.
Results
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 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.
Abbreviations and acronyms
C
controls
CAN
cardiovascular autonomic neuropathy
CPT
cold pressor testing
CRP
C-reactive peptide
DC
diabetic control subjects
DMA+
early microangiopathy
LV
left ventricle/ventricular
MBF
myocardial blood flow
PET
positron emission tomography
vWF
von Willebrand factor
([11C]HED)
[11C]meta-hydroxyephedrine
Cited by (0)
This work was supported in part by grants from the Juvenile Diabetes Research Foundation (to Dr. Stevens), the National Institutes of Health R01-DK52391 (to Dr. Stevens), a Veterans Administration Career Development Award (to Dr. Stevens), American Diabetes Association (to Dr. Stevens), and a University of Michigan General Clinical Research Center (GCRC) grant (to Dr. Stevens). The first two authors contributed equally to these studies.
