Beyond HbA1c: Comparing Glycemic Variability and Glycemic Indices in Predicting Hypoglycemia in Type 1 and Type 2 Diabetes

Abstract

Background: Hypoglycemia is the major impediment to therapy intensification in diabetes. Although higher individualized HbA1c targets are perceived to reduce the risk of hypoglycemia in those at risk of hypoglycemia, HbA1c itself is a poor predictor of hypoglycemia. We assessed the use of glycemic variability (GV) and glycemic indices as independent predictors of hypoglycemia.

Methods: A retrospective observational study of 60 type 1 and 100 type 2 diabetes subjects. All underwent professional continuous glucose monitoring (CGM) for 3-6 days and recorded self-monitored blood glucose (SMBG). Indices were calculated from both CGM and SMBG. Statistical analyses included regression and area under receiver operator curve (AUC) analyses.

Results: Hypoglycemia frequency (53.3% vs. 24%, P < 0.05) and %CV (40.1% ± 10% vs. 29.4% ± 7.8%, P < 0.001) were significantly higher in type 1 diabetes compared with type 2 diabetes. HbA1c was, at best, a weak predictor of hypoglycemia. %CV_CGM, Low Blood Glucose Index (LBGI)_CGM, Glycemic Risk Assessment Diabetes Equation (GRADE)Hypoglycemia_CGM, and Hypoglycemia Index_CGM predicted hypoglycemia well. %CV_CGM and %CV_SMBG consistently remained a robust discriminator of hypoglycemia in type 1 diabetes (AUC 0.88). In type 2 diabetes, a combination of HbA1c and %CV_SMBG or LBGI_SMBG could help discriminate hypoglycemia.

Conclusion: Assessment of glycemia should go beyond HbA1c and incorporate measures of GV and glycemic indices. %CV_SMBG in type 1 diabetes and LBGI_SMBG or a combination of HbA1c and %CV_SMBG in type 2 diabetes discriminated hypoglycemia well. In defining hypoglycemia risk using GV and glycemic indices, diabetes subtypes and data source (CGM vs. SMBG) must be considered.

Keywords: Coefficient of variation; Continuous glucose monitoring; Glycemic variability; Hypoglycemia; Self-monitored blood glucose.