title: Effects of metabolic and myocardial microcirculatory abnormalities on the pathogenesis of cardiac autonomic neuropathy in type 2 diabetes mellitus: A prospective study in Japanese patients.
abstract: BACKGROUND
  In diabetic patients, cardiac autonomic neuropathy is an important factor affecting prognosis. Whether this condition in diabetic patients is caused directly by neurovisceral metabolic disorder and/or indirectly by micro circulation remains to be clarified.
  
  
  OBJECTIVE
  The aim of this study was to determine whether cardiac sympathetic nerve dysfunction can be detected using adenosine triphosphate (ATP) testing, while also investigating the effects of metabolic and/or myocardial microcirculatory abnormalities on the pathogenesis of cardiac autonomic nerve dysfunction in patients with type 2 diabetes mellitus (DM-2) in Japan.
  
  
  METHODS
  This prospective study was performed at the Division of Diabetology Department of Internal Medicine, Toho University, Ohashi Hospital, Tokyo, Japan. Patients aged ≥ 18 years with DM-2 with no abnormalities on electrocardiography (ECG) or echocardiography were enrolled. An ATP thallium (Tl)-201 myocardial scintigraphy test (ATP test) and iodine (I)-123 metaiodobenzylguanidine (MIBG) scintigraphy were performed. ATP was administered by continuous IV infusion over 6 minutes at 0.16 mg/kg · min. Five minutes after the ATP infusion was started, T1-201 111 MBq IV was administered. Single-photon emission computed tomography (SPECT) imaging was begun immediately after the end of ATP infusion and was completed 3 hours after stress to show washout from stress to rest. I-123 MIBG 111 MBq IV was administered. A planar image from the front side and a SPECT image (early phase) was obtained 15 to 30 minutes later. After 3 hours, a planar image from the front side and a SPECT image (late phase) were obtained to show washout from stress to rest. The mean TI washout rate (ATP-WR) and heart-to-mediastinum (H/M) ratio in the late-phase scintigraphic images and the washout rate of MIBG (MIBG-WR) in the left ventricle was determined. The correlations of these measurements with the mean values of glycosylated hemoglobin (HbA1c) and fasting plasma glucose obtained from monthly measurements over the previous 6 and 24 months were determined.
  
  
  RESULTS
  A total of 25 patients were enrolled (13 men, 12 women; mean [SD] age, 59.86 [8.28] years). Significant negative correlations between both ATP-WR and MIBG-WR and HbA1c were found (r = -0.52 [P = 0.02] and -0.47 [P = 0.03], respectively). Although no correlation was found between ATP-WR values and the early phase H/M ratio, a significant positive correlation was observed between ATP-WR and H/M ratio (r = 0.54; P = 0.02).
  
  
  CONCLUSIONS
  In the present study in Japanese diabetic patients without subjective signs of coronary artery disease and without abnormalities on ECG or echocardiography, ATP-WR, an indicator of myocardial blood flow, was correlated with myocardial sympathetic nerve dysfunction and 24-month glycemic control. However, sympathetic nerve dysfunction was not correlated with 24-month glycemic control.
authors.affiliation: Division of Diabetology, Department of Internal Medicine, Toho University, Ohashi Hospital, Tokyo, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Komori
keywords: ATP T1-201 myocardial scintigraphy; I-123 metaiodobenzylguanidine scintigraphy; cardiac sympathetic nervous dysfunction; glycemic control