Cardiac sympathetic imaging in the diagnosis of cardiac autonomic neuropathy in pre-diabetes

Abstract

Cardiac autonomic neuropathy is a common and frequently underdiagnosed complication of diabetes with significant associated cardiovascular morbidity and mortality. The reported prevalence of cardiac autonomic neuropathy, although extensively studied and reported in both type 1 and 2 diabetes, has been variable due to a variety of available testing methods as well as different diagnostic criteria used. The Toronto Consensus Panel recently published guidelines for diagnosing and classifying cardiac autonomic neuropathy using previously known non-invasive tools for cardiovascular reflex testing. The American Diabetes Association also considers these cardiovascular reflex tests to be sensitive and specific for diagnosing cardiac autonomic neuropathy, and therefore, the current standard for evaluating both sympathetic and parasympathetic function. Cardiac autonomic neuropathy is not as well studied in pre-diabetic states of impaired glucose tolerance (IGT) and impaired fasting glucose, as it is in types 1 and 2 diabetes. There is, however, a growing body of evidence suggesting that a significant number of patients may have developed cardiac autonomic neuropathy during their prediabetes stage even before development of diabetes. A study by Vinek et al concluded that as many as 7% of patients have cardiac autonomic neuropathy at the time of initial diagnosis of type 1 or 2 diabetes. This finding suggests that a significant proportion of patients may have developed cardiac autonomic neuropathy during their prediabetes stage. This is also supported by the likely chronicity of the most widely accepted mechanisms of pathogenesis of cardiac autonomic neuropathy resulting from neuronal cellular injury, inflammation, microvascular ischemia, autoimmunity, and oxidative stress induced neuron death directly or indirectly triggered by a hyperglycemic state. The role of I-123 metaiodobenzylguanidine (MIBG) imaging in diabetic patients is well studied, and findings from several studies in this field suggest that impaired heart-to-mediastinum (H/M) ratio and washout rate (WR) of MIBG correlate well with the presence or absence of clinical autonomic neuropathy in diabetic patients. Similar data assessing the relationship of cardiac MIBG activity to cardiac autonomic neuropathy in pre-diabetes is very limited. The only major previous study employing I-123 MIBG and assessing it as a reliable tool for evaluating the sympathetic arm of cardiac autonomic function in pre-diabetes was reported by Diakakis et al. In the present study, Asghar and associates tested the prevalence of cardiac autonomic neuropathy in patients with IGT using conventional methods of cardiac autonomic reflex testing as well as cardiac adrenergic innervation using imaging with I-123 MIBG. Their study concludes that there is no difference in cardiac autonomic function or cardiac sympathetic innervation among 15 controls and 15 subjects with IGT. The study is well designed, and the method of selection of patients with IGT (serum glucose at 2-hour post oral challenge 7.8-11.1 mmol/L or 140-200 mg/dL) is in accordance with the standards recommended by American Diabetes Association and American College of Endocrinology for diagnosis of IGT. Nevertheless, Reprint requests: Myron C. Gerson, MD, Division of Cardiovascular Health and Disease, Department of Internal Medicine, University of Cincinnati College of Medicine, P.O. Box 670542, Cincinnati, OH 45267-0542; myron.gerson@uc.edu J Nucl Cardiol 2015;22:1269–72. 1071-3581/$34.00 Copyright 2015 American Society of Nuclear Cardiology.