Association Between Impaired Cardiovascular Autonomic Function and Hypoglycemia in Patients With Type 1 Diabetes

OBJECTIVE We studied the association between glycemic variability (GV) reflecting hypoglycemic stress and cardiovascular autonomic function in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODS Forty-four type 1 diabetic patients (mean age 34 +/- 13 years, 40% male, 86% Caucasian, mean diabetes duration 13 +/- 6 years, mean hemoglobin A(1c) [HbA(1c)] 8.0 +/- 1.2% [64 +/- 5 mmol/mol]) without cardiovascular disease, dyslipidemia, or hypertension participated in this pilot study. Indices of GV reflective of hypoglycemic stress (low blood glucose index [LBGI] and area under the curve [AUC] for hypoglycemia) were computed using data obtained during 5-day continuous glucose monitoring. Cardiovascular autonomic neuropathy (CAN) was assessed using standardized cardiovascular reflex testing and measures of heart rate variability (HRV), which were analyzed as time and frequency domain measures. RESULTS Both LBGI and AUC hypoglycemia had a significant negative association with the low-frequency power of HRV (r = -0.47, P = 0.002; r = 20.43, P = 0.005, respectively) and with the high-frequency power of HRV (r = -0.37, P = 0.018; r = -0.38, P = 0.015, respectively). These inverse associations persisted after adjusting for HbA(1c), although they were attenuated in multivariable analysis after adjustment for age, diabetes duration, and several other covariates. CONCLUSIONS Increased GV promoting hypoglycemic stress was associated with reduced HRV independent of glycemic control as assessed by HbA(1c). These pilot data suggest that glucose variability may contribute to cardiovascular autonomic dysfunction among adults with type 1 diabetes.