The Association Between Continuous Glucose Monitoring-Derived Metrics and Cardiovascular Autonomic Neuropathy in Outpatients with Type 2 Diabetes

Background: Continuous glucose monitoring (CGM)-derived metrics, including time in range (TIR), are attracting attention as new indicators, beyond hemoglobin A1c, of glycemic control and diabetes complications. This study investigated the associations between CGM-derived TIR, hyperglycemia, and hypoglycemia metrics and cardiovascular autonomic neuropathy (CAN) in patients with type 2 diabetes. Methods: A total of 284 patients with type 2 diabetes who underwent CGM using GOLD (TM) (Medtronic MiniMed) for 3 days or iPro (TM) 2 (Medtronic MiniMed) for 6 days and autonomic function tests within 3 months based on outpatient data were recruited. The definition of CGM-derived metrics was subject to the most recent international consensus. CAN was defined as an abnormal result in two or more parasympathetic test, and the severity of CAN was estimated as the sum of the scores of the five cardiovascular autonomic function tests. Results: A total of 84 patients (29.6%) were diagnosed with CAN, and the mean TIR was 57.0% +/- 7.0%. A multiple logistic regression analysis revealed that the odds ratio (OR) of presence of CAN was 0.876 [95% confidence interval (CI): 0.79-0.98] per 10% increase in the TIR 70-180 mg/dL, after adjusting for age, sex, diabetes duration, any medications, and glycemic variability. A 10% increase in the TIR was significantly inversely associated with the severity of CAN (OR: 0.89, 95% CI: 0.81-0.98). Among the metrics of hyperglycemia, each 10% increase in a time above range (TAR) >180 mg/dL was also independently correlated with the presence of CAN (OR: 1.141, 97.5% CI: 1.01-1.29) and the severity of CAN (OR: 1.13, 97.5% CI: 1.01-1.26). Conclusion: A TIR 70-180 mg/dL and a TAR >180 mg/dL were significantly associated with CAN in outpatients with type 2 diabetes.