The relation between HbA1c and hypoglycemia revisited; a secondary analysis from an intervention trial in patients with type 1 diabetes and impaired awareness of hypoglycemia.

AIMS: We aimed to re-assess the previously shown but recently disputed association between HbA1c and severe hypoglycemia.

METHODS: 52 Patients with T1D and IAH participated in an earlier reported randomized, crossover trial with two 16-week intervention periods comparing continuous glucose monitoring (CGM) with self-monitoring of blood glucose (SMBG). In this previous study, time spent in normoglycemia (the primary outcome), was improved by 9.6% (p<0.0001). We performed post-hoc analyses using a zero-inflated Poisson regression model to assess the relationship between severe hypoglycemia and HbA1c, glucose variability and duration of diabetes.

RESULTS: During SMBG use, HbA1c and the number of severe hypoglycemic events were negatively associated (OR 0.20 [95% CI 0.09 to 0.44]). During CGM use, this relationship showed an odds ratio of 0.65 (95% CI 0.42 to 1.01). There was no significant relationship between glucose variability or duration of diabetes and severe hypoglycemia.

CONCLUSIONS: In patients with T1D and IAH, treated with standard SMBG, a negative association exists between HbA1c and the number of severe hypoglycemic events. Thus, reaching target HbA1c values still comes with a higher risk of severe hypoglycemia. CGM weakens this association, suggesting CGM enables patients to reach their target HbA1c more safely.