Autonomic dysfunction and risk of severe hypoglycemia among individuals with type 2 diabetes.

There is limited data on the link between cardiac autonomic neuropathy (CAN) and severe hypoglycemia, in type 2 diabetes. We evaluated the associations of CAN with severe hypoglycemia among 7,421 adults with type 2 diabetes from the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study. CAN was defined using electrocardiogram-derived measures. Cox and Andersen-Gill regression models were used to generate hazard ratios (HRs) for first and recurrent severe hypoglycemic episodes, respectively. Over 4.7 years, there were 558 first and 811 recurrent hypoglycemic events. Participants with CAN had increased risks of first (HR 1.23, 95%CI 1.01-1.50) or recurrent (HR: 1.46, 95%CI 1.16-1.84) episodes of severe hypoglycemia. The intensity of glycemic management modified the CAN association with hypoglycemia (P for interaction <0.05). In the standard glycemic management group, compared to participants without CAN, HRs for first severe hypoglycemia and recurrent hypoglycemia were 1.58 (95%CI 1.13-2.23) and 1.96 (1.33-2.90). In the intensive glycemic management group, HRs for first severe hypoglycemia and recurrent hypoglycemia were 1.10 (0.86-1.40) and 1.24 (0.93-1.65). In summary, CAN was independently associated with higher risks of first and recurrent hypoglycemia among adults with type 2 diabetes, with the highest risk observed among those on standard glycemic management.