Sympathetic dysfunction in type 1 diabetes: association with impaired myocardial blood flow reserve and diastolic dysfunction

J Am Coll Cardiol. 2004 Dec 21;44(12):2368-74. doi: 10.1016/j.jacc.2004.09.033.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine / pharmacology
  • Adult
  • Autonomic Nervous System Diseases / etiology
  • Autonomic Nervous System Diseases / physiopathology*
  • C-Reactive Protein / metabolism
  • Carbon Radioisotopes
  • Contrast Media
  • Coronary Circulation* / drug effects
  • Diabetes Mellitus, Type 1* / complications
  • Diabetic Angiopathies / complications
  • Diabetic Angiopathies / etiology
  • Diabetic Angiopathies / physiopathology*
  • Diabetic Neuropathies / etiology
  • Diabetic Neuropathies / physiopathology*
  • Diastole
  • Ephedrine / analogs & derivatives*
  • Female
  • Heart / physiopathology*
  • Heart Conduction System / physiopathology*
  • Hemodynamics / drug effects
  • Humans
  • Male
  • Middle Aged
  • Norepinephrine / blood
  • Oxidative Stress
  • Vasoconstriction
  • Ventricular Dysfunction, Left / etiology
  • von Willebrand Factor / metabolism

Substances

  • Carbon Radioisotopes
  • Contrast Media
  • von Willebrand Factor
  • 3-hydroxyephedrine
  • C-Reactive Protein
  • Ephedrine
  • Adenosine
  • Norepinephrine