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CLINICAL RESEARCH: DIABETES AND THE HEART

Sympathetic dysfunction in type 1 diabetes

Association with impaired myocardial blood flow reserve and diastolic dysfunction

Rodica Pop-Busui, MD^*,, Ian Kirkwood, MBBS^*, Helena Schmid, MD^*, Victor Marinescu, BS^*, Justin Schroeder, BS^*, Dennis Larkin, BS^*, Elina Yamada, MD, David M. Raffel, PhD and Martin J. Stevens, MD^*,*

^* Endocrinology and Metabolism
Cardiology
Nuclear Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical College of Ohio, Toledo, Ohio

Manuscript received November 24, 2003; revised manuscript received July 2, 2004, accepted September 14, 2004.

^* Reprint requests and correspondence: Dr. Martin J. Stevens, Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan, 5570 MSRB II, Box 0678, 1150 West Medical Center Drive, Ann Arbor, Michigan 48109-0678 (Email: stevensm{at}umich.edu).

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). [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

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