Revisiting the Relationships Between Measures of Glycemic Control and Hypoglycemia in Continuous Glucose Monitoring Data Sets

Abstract

OBJECTIVE The Diabetes Control and Complications Trial (DCCT) identified an inverse relationship between HbA1c and severe hypoglycemia. We investigated the relationship between hypoglycemia and HbA1c in a large type 1 diabetes cohort on multiple daily injection or insulin pump therapy using blinded continuous glucose monitoring (CGM) data. The impact of real-time CGM on these relationships and how these relationships differ with biochemical definitions of hypoglycemia have also been assessed. RESEARCH DESIGN AND METHODS CGM data were obtained from the JDRF CGM randomized control trial. Baseline blinded CGM data were used to assess time in hypoglycemia in all individuals. End point data from the CGM intervention group were used to assess the impact of CGM. Percentage of time spent below 3.9, 3.3, 3.0, and 2.8 mmol/L were calculated and quadratic regression plots drawn. Relationships were analyzed visually, and ANOVA was used to assess relationships between glycemia and time below threshold. RESULTS J-shaped relationships were observed for all biochemical hypoglycemia thresholds, with the lowest hypoglycemia risk occurring at HbA1c values between 8.1 and 8.6% (65–70 mmol/mol). The use of an average of 5 days/week of CGM flattened the relationships for 3.3, 3.0, and 2.8 mmol/L, and ANOVA confirmed the loss of relationship for the 3.3 mmol/L threshold using CGM. CONCLUSIONS The relationship between hypoglycemia and HbA1c in a population with type 1 diabetes is J-shaped. Lower HbA1c values are still associated with increased hypoglycemia risk, although the magnitude of risk depends on biochemical threshold. Real-time CGM may reduce the percentage time spent in hypoglycemia, changing the relationship between HbA1c and hypoglycemia.