Cardiovascular Autonomic Dysfunction Predicts Severe Hypoglycemia in Patients With Type 2 Diabetes: A 10-Year Follow-up Study

OBJECTIVE The aim of this study was to investigate the development of severe hypoglycemia (SH) in the presence of cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS From January 2001 to December 2002, a total of 894 patients with type 2 diabetes were enrolled. A cardiovascular autonomic function test (AFT) was performed using the following heart rate variability parameters: expiration-to-inspiration ratio, response to Valsalva maneuver, and standing. From the results for each of the three tests (0 for normal, 1 for abnormal), a total AFT score of 1 was defined as early CAN, and an AFT score of ≥2 was defined as definite CAN. RESULTS The median follow-up time was 9.5 years. The mean age was 54.5 ± 10.1 years, and the mean duration of diabetes was 8.9 ± 6.3 years. One hundred ninety-six patients (31.4%) showed an abnormal cardiovascular AFT score at baseline. Sixty-two patients (9.9%) experienced 77 episodes of SH (1.33 per 100 patient-years). The number of SH events increased as the CAN score increased (23 patients [5.4%] with normal score; 17 patients [17.2%] with early CAN; and 22 patients [22.7%] with definite CAN; P for trends < 0.001). Cox proportional hazards regression analysis revealed that SH was associated with definite CAN (normal vs. definite CAN: hazard ratio 2.43 [95% CI 1.21-4.84]; P = 0.012). CONCLUSIONS Definite CAN was an independent prognostic factor for the development of SH in patients with type 2 diabetes.