title: Sympathetic dysfunction in type 1 diabetes: association with impaired myocardial blood flow reserve and diastolic dysfunction.
abstract: OBJECTIVE
  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.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0678, USA.
authors.forename: Rodica
authors.initials: R
authors.lastname: Pop-Busui
authors.forename: Ian
authors.initials: I
authors.lastname: Kirkwood
authors.forename: Helena
authors.initials: H
authors.lastname: Schmid
authors.forename: Victor
authors.initials: V
authors.lastname: Marinescu
authors.forename: Justin
authors.initials: J
authors.lastname: Schroeder
authors.forename: Dennis
authors.initials: D
authors.lastname: Larkin
authors.forename: Elina
authors.initials: E
authors.lastname: Yamada
authors.forename: David M
authors.initials: DM
authors.lastname: Raffel
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Stevens
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000328:Adult; D001342:Autonomic Nervous System Diseases / Q000209:etiology / Q000503:physiopathology*; D002097:C-Reactive Protein / Q000378:metabolism; D002250:Carbon Radioisotopes; D003287:Contrast Media; D003326:Coronary Circulation / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000150:complications; D003925:Diabetic Angiopathies / Q000150:complications / Q000209:etiology / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000209:etiology / Q000503:physiopathology*; D003971:Diastole; D004809:Ephedrine / Q000031:analogs & derivatives*; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006329:Heart Conduction System / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D018384:Oxidative Stress; D014661:Vasoconstriction; D018487:Ventricular Dysfunction, Left / Q000209:etiology; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D002250:Carbon Radioisotopes; D003287:Contrast Media; D014841:von Willebrand Factor; C065363:3-hydroxyephedrine; D002097:C-Reactive Protein; D004809:Ephedrine; D000241:Adenosine; D009638:Norepinephrine