Cardiac sympathetic dysinnervation in Type 2 diabetes mellitus with and without ECG-based cardiac autonomic neuropathy

Abstract

To evaluate the presence and extent of global and regional distributions of cardiac sympathetic dysinnervation in Type 2 diabetes mellitus I-123-metaiodobenzylguanidine (I-123-MIBG) scintigraphy was applied to 15 Type 2 (noninsulin-dependent) diabetic patients with ECG-based cardiac autonomic neuropathy (≥two of five age-related cardiac reflex tests abnormal) and 15 clinically comparable Type 2 diabetic patients without ECG-based cardiac autonomic neuropathy. Myocardial perfusion abnormalities were excluded by 99m-Tc-methoxyisobutylisonitrile (99m-MIBI) scintigraphy. Both in Type 2 diabetic patients with and without, ECG-based autonomic neuropathy, only one patient (7%) was found to have a normal homogeneous uptake of I-123-MIBG compared to 14 patients (93%) with a reduced I-123-MIBG uptake. The uptake of I-123-MIBG in the posterior myocardium of diabetic patients was smaller than in the anterior, lateral, and septal myocardium (P<.001, P<.001, P<.001, respectively). Diabetic patients with ECG-based cardiac autonomic neuropathy demonstrated a more pronounced reduction of the posterior I-123-MIBG myocardial uptake than diabetic patients without (P<.01). The mean global and the anterior, lateral, septal, and apical myocardial I-123-MIBG uptake was comparable between the two groups. The uptake of the posterior myocardial region correlated with all indices of heart rate variation at rest and during deep breathing. A correlation between global or regional myocardial I-123-MIBG uptake and QT interval was not observed. The study demonstrates that cardiac sympathetic dysinnervation is common in Type 2 diabetes mellitus both with and without ECG-based cardiac autonomic neuropathy. In Type 2 diabetes mellitus, the posterior myocardium is predominantly affected and the extent of dysinnervation is more pronounced in the presence of ECG-based cardiac autonomic neuropathy.

Introduction

The balance of activity between the cardiac sympathetic and parasympathetic nervous system has a key role for the functional and structural performance of the diabetic heart (Standl & Schnell, 2000). In diabetic patients, the frequent dysfunction of the cardiac autonomic nervous system determines to a large extent the poor outcome Aronson et al., 1997, Di Carli et al., 1999, Lauer et al., 1993, Weston & Gill, 1999.

Single-photon emission computed tomography (SPECT) with I-123-metaiodobenzylguanidine (I-123-MIBG) has been introduced to directly assess global and regional distributions of cardiac sympathetic innervation Kline et al., 1981, Kreiner et al., 1995, Mantysaari et al., 1992, Schnell et al., 1995, Sisson et al., 1987. The integrity and/or the function of sympathetic postganglionary presynaptic neurons is reflected by the uptake of I-123-MIBG, since the guanethidine analogue MIBG shares the same active uptake, storage, and release mechanisms as noradrenaline Sisson et al., 1987, Tobes et al., 1985, Wellman & Zipes, 1990. Dual tracer scintigraphy with application of I-123-MIBG and 99m-MIBI combines assessment of both cardiac sympathetic innervation and myocardial perfusion and therefore, further increases the diagnostic value of the scintigraphic technique Schnell et al., 1995, Tobes et al., 1985, Wellman & Zipes, 1990.

In Type 1 diabetes mellitus, the pattern of cardiac sympathetic dysinnervation, as assessed by I-123-MIBG scintigraphy, has been demonstrated to be heterogeneous and to be dominated by defects in the posterior myocardial region Kreiner et al., 1995, Schnell et al., 1995, Schnell et al., 1996b. A reduced myocardial I-123-MIBG uptake has also been suggested for Type 2 diabetic patients both with and without myocardial damage Langer et al., 1995, Mantysaari et al., 1992, Nagamachi et al., 1998, Hattori et al., 1996.

The aim of the present study was to (1) evaluate the pattern and extent of global and regional sympathetic cardiac innervation by means of I-123-MIBG scintigraphy in Type 2 diabetic patients without myocardial perfusion defects (99m-MIBI-scintigraphy), (2) analyse the observations with regard to the presence of ECG-based cardiac autonomic neuropathy, and (3) compare the findings with indices of five cardiac reflex tests and QTc interval.