Acta Diabetol 28: 199-202, 1992 ACTA DIABETOLOGICA 9 Springer-Verlag 1992 Asymptomatic coronary artery disease in diabetes: associated with autonomic neuropathy? M. Juhani Koistinen, K.E. Juhani Airaksinen, Heikki V. Huikuri, Heikki Pirttiaho, Markku K. Linnaluoto, Markku J. Ik~iheimo, and Juha 1". Takkunen Division of Cardiology, Department of Medicine, Oulu University, SF-90220 Oulu, Finland Abstract. To elucidate the potential association of dia- betic autonomic neuropathy with increased prevalence of silent coronary artery disease (CAD), 138 asymptomatic diabetic subjects were screened using exercise ECG. 24-h ambulatory ECG and dynamic thallium scintigraphy. Fourteen patients with exercise-induced myocardial is- chaemia and angiographically confirmed CAD (> 50% coronary artery narrowing) were found using this proto- col. Their autonomic nervous function was assessed using standard cardiovascular tests and compared with that of 23 consecutive diabetic patients catheterised because of symptomatic CAD (mean New York Heart Association class 3.0). The diabetic patients with symptomatic CAD had more severe coronary atherosclerosis than the dia- betic patients with asymptomatic CAD assessed by jeop- ardy score (P < 0.01). The groups did not, however, differ with respect to autonomic function tests. Five patients (22%) with symptomatic CAD and 3 patients (21%) with asymptomatic CAD had definite autonomic dysfunction, i.e. two or more abnormal tests. Thus, our results suggest that the frequency of autonomic neuropathy is not in- creased in diabetic patients with asymptomatic CAD. The contribution of diabetic autonomic neuropathy to the absence of cardiac pain needs further clinical and pathological studies. Key words: Diabetes mellitus - Asymptomatic coronary artery disease - Diabetic neuropathy - Autonomic ner- vous function Introduction Epidemiological studies have shown that the various manifestations of coronary artery disease (CAD) are in- creased in diabetic populations [1]. The early study of Bradley and Schonfeld [2] showed that diabetic patients more often experience little or no pain during myocardial Offprint requests to: M. J. Koistinen infarction. A trend toward an increased incidence of painless myocardial infarction in diabetic patients was also found in the Framingham study [3], but a later epi- demiological study could not confirm this relationship [4]. Numerous studies have shown that asymptomatic diabetic patients have abnormal exercise ECGs more of- ten than non-diabetic subjects [5 9]. The greater inci- dence of silent myocardial infarctions and ischaemia has been attributed to damage to the autonomic nerve fibres in the myocardium responsible for mediating cardiac pain [10-12]. This relationship is, however, not clearly established because even patients with advanced auto- nomic neuropathy may develop severe pain during acute myocardial infarction [13]. To elucidate the potential association of diabetic auto- nomic neuropathy with the increased prevalence of asymptomatic CAD in diabetes, the autonomic nervous function and coronary anatomy of diabetic patients with asymptomatic CAD were compared with those of dia- betic patients with symptomatic CAD referred for coro- nary angiography because of chest pain. Patients and methods Patients This survey is part of a wider research project in progress in our institution to assess asymptomatic heart disease in patients with diabetes mellitus. To find diabetic patients with asymptomatic CAD an invitation letter was sent to 338 diabetic members of the local diabetic association. Of these, 170 were unwilling to participate and 30 did not fulfil the inclusion criteria of this part of the study, which were: (1) age 35 to 60 years, (2) duration of type 1 (insulin-depen- dent) diabetes 5 years or more and no uncontrolled proliferative retinopathy or serum creatinine greater than 200 ktmol/1, (3) no symptoms of ischaemic heart disease using the Rose questionnaire [14], and (4) no other systemic diseases or medication which might affect cardiac function or invalidate maximal exercise test. As a result, 138 diabetic patients participated in the non-invasive screening to discover those with asymptomatic CAD (group 1). They underwent exercise ECG, dynamic thallium scintigraphy and 24-h ECG. Exercise ECG failed in 1 patient, thallium scintigraphy