The Impact of Frequent and Unrecognized Hypoglycemia on Mortality in the ACCORD Study

OBJECTIVE-The aim of this study was to examine the relationship between frequent and unrecognized hypoglycemia and mortality in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study cohort. RESEARCH DESIGN AND METHODS-A total of 10,096 ACCORD study participants with follow-up for both hypoglycemia and mortality were included. Hazard ratios (95% CIs) relating the risk of death to the updated annualized number of hypoglycemic episodes and the updated annualized number of intervals with unrecognized hypoglycemia were obtained using Cox proportional hazards regression models, allowing for these hypoglycemia variables as time-dependent covariates and controlling for the baseline covariates. RESULTS-Participants in the intensive group reported a mean of 1.06 hypoglycemic episodes (self-monitored blood glucose <70 mg/dL or <3.9 mmol/L) in the 7 days preceding their regular 4-month visit, whereas participants in the standard group reported an average of 0.29 episodes. Unrecognized hypoglycemia was reported, on average, at 5.8% of the intensive group 4-month visits and 2.6% of the standard group visits. Hazard ratios for mortality in models including frequency of hypoglycemic episodes were 0.93 (95% CI 0.9-0.97; P < 0.001) for participants in the intensive group and 0.98 (0.91-1.06; P = 0.615) for participants in the standard group. The hazard ratios for mortality in models, including unrecognized hypoglycemia, were not statistically significant for either group. CONCLUSIONS-Recognized and unrecognized hypoglycemia was more common in the intensive group than in the standard group. In the intensive group of the ACCORD study, a small but statistically significant inverse relationship of uncertain clinical importance was identified between the number of hypoglycemic episodes and the risk of death among participants.