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 |
|
This article has been cited by other articles:
|
|
|
|
 
G. N. Shivu, K. Abozguia, T. T. Phan, I. Ahmed, R. Weaver, P. Narendran, M. Stevens, and M. Frenneaux
Increased Left Ventricular Torsion in Uncomplicated Type 1 Diabetic Patients: The role of coronary microvascular function
Diabetes Care,
September 1, 2009;
32(9):
1710 - 1712.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. R. Schelbert
Coronary circulatory function abnormalities in insulin resistance insights from positron emission tomography.
J. Am. Coll. Cardiol.,
February 3, 2009;
53(5 Suppl):
S3 - S8.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. P. Kellogg, K. Converso, T. Wiggin, M. Stevens, and R. Pop-Busui
Effects of cyclooxygenase-2 gene inactivation on cardiac autonomic and left ventricular function in experimental diabetes
Am J Physiol Heart Circ Physiol,
February 1, 2009;
296(2):
H453 - H461.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. B. Dokken
The Pathophysiology of Cardiovascular Disease and Diabetes: Beyond Blood Pressure and Lipids
Diabetes Spectr,
July 1, 2008;
21(3):
160 - 165.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Z. T. Bloomgarden
Diabetic Neuropathy
Diabetes Care,
March 1, 2008;
31(3):
616 - 621.
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. M. Witteles and M. B. Fowler
Insulin-Resistant Cardiomyopathy: Clinical Evidence, Mechanisms, and Treatment Options
J. Am. Coll. Cardiol.,
January 15, 2008;
51(2):
93 - 102.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. T. Thackeray, R. S. Beanlands, and J. N. DaSilva
Presence of Specific 11C-meta-Hydroxyephedrine Retention in Heart, Lung, Pancreas, and Brown Adipose Tissue
J. Nucl. Med.,
October 1, 2007;
48(10):
1733 - 1740.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T H Schindler, A D Facta, J O Prior, J Cadenas, W A Hsueh, M J Quinones, and H R Schelbert
Improvement in coronary vascular dysfunction produced with euglycaemic control in patients with type 2 diabetes
Heart,
March 1, 2007;
93(3):
345 - 349.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. M. Madsen, H. M. Sondergaard, M. Bottcher, N. H. Buus, O. Schmitz, H. E. Botker, and T. T. Nielsen
Impact of Type 2 Diabetes on Nitric Oxide and Adrenergic Modulation of Myocardial Perfusion
Diabetes,
February 1, 2007;
56(2):
468 - 475.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. I. Vinik and D. Ziegler
Diabetic Cardiovascular Autonomic Neuropathy
Circulation,
January 23, 2007;
115(3):
387 - 397.
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. G. Poornima, P. Parikh, and R. P. Shannon
Diabetic Cardiomyopathy: The Search for a Unifying Hypothesis
Circ. Res.,
March 17, 2006;
98(5):
596 - 605.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. H. Schindler, E. U. Nitzsche, H. R. Schelbert, M. Olschewski, J. Sayre, M. Mix, I. Brink, X.-L. Zhang, M. Kreissl, N. Magosaki, et al.
Positron Emission Tomography-Measured Abnormal Responses of Myocardial Blood Flow to Sympathetic Stimulation Are Associated With the Risk of Developing Cardiovascular Events
J. Am. Coll. Cardiol.,
May 3, 2005;
45(9):
1505 - 1512.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
