Screening of Autonomic Neuropathy in Patients with Type 2 Diabetes

Corresponding author: Bo Kyung Koo Department of Internal Medicine, Boramae Medical Center, Seoul National University College of Medicine, 20 Boramae-ro 5-gil, Dongjak-gu, Seoul 156-707, Korea E-mail: [email protected] Diabetic autonomic neuropathy (DAN) causes morbidity and mortality in patients with diabetes mellitus [1-4]; and among DAN, cardiac autonomic neuropathy (CAN) is an independent risk factor for cardiovascular mortality [5,6]. Although there has been very limited epidemiologic data in Korea, more than 50 % of patients with type 2 diabetes mellitus (T2DM) were reported to have DAN in Korea [4,7]. Furthermore, 45.3% of patients with newly detected T2DM had DAN at the time of diagnosis [7]. Current guideline or expert opinions recommend that screening for DAN should be instituted at diagnosis of type 2 diabetes [8-10], even for those who don’t have any symptom of DAN [10]. As CAN is the most studied and clinically important form of DAN, noninvasive tests for CAN are recommended for DAN screening: response to deep breathing, standing, and Valsalva maneuver, and postural blood pressure testing [8,10,11]. Early stages of CAN may be completely asymptomatic and detected only by cardiovascular reflex tests (heart rate variability [HRV] to deep breathing and standing and Valsalva maneuver). HRV can also be assessed by spectral analysis of a series of successive R-R intervals, which can be measured across a range of frequencies and needs less patient participation [12,13]. Quantitative scintigraphic assessment of sympathetic innervation of the human heart [13,14] or quantitative regional measurements of myocardial β-adrenoreceptor density [15] can also be used for the assessment of CAN, of which the results are associated with cardiovascular risks [16]. Other than CAN, DAN also involves gastrointestinal, genitourinary, sudomotor or ocular systems and can be assessed by specific tests associated with its symptoms [10,11]. After identifying individuals at risk of DAN, effective management should be provided. However, at present, the treatment for DAN is limited to glucose control and symptom-based management. The Diabetes Control and Complications Trial demonstrated that intensification of glycemic control can reduce the incidence of CAN by 53% compared with conventional therapy [17]; and Steno-2 study showed that an intensive multifactorial cardiovascular risk intervention targeting blood pressure, lipid, smoking, and lifestyle factors as well as glucose control reduced the progression and development of CAN among T2DM patients [18]. However, multifactorial cardiovascular risk intervention with appropriate glucose control is recommended even for T2DM patients without CAN [8]. Intervention targeting DAN pathogenesis is very limited. A 4-month, randomized controlled clinical trial demonstrated that an antioxidant, α-lipoic acid, significantly improves CAN in patients with T2DM [19]. ACE-I or ARB also improved DAN in asymptomatic patients with T2DM patients [20]; however, most T2DM use them to manage blood pressure [8]. In diabetic animal model, peroxynitrite decomposition catalysts [21,22] and a selective tyrosine nitration inhibitor [23] have been reported to show neuroprotective effects. However, there has been limited translational works in diabetic patients, and no effective long-term treatment exists to date. Editorial Complications