Association of glycation gap with hypoglycemia CGM indices in Japanese patients with type 2 diabetes mellitus

The glycation gap (GGap), defined as the discrepancy between glycated hemoglobin (HbA1c) and the value estimated from actual blood glucose level, is associated with diabetic complications, but its association with hypoglycemia remains unclear. We evaluated the association between GGap and continuous glucose monitoring (CGM)-based hypoglycemic indices in patients with type 2 diabetes mellitus (T2DM). Baseline data from a multicenter cohort of 999 T2DM patients without cardiovascular disease were analyzed. The difference between HbA1c and estimated A1c (eA1c) was defined as the GGap, and various CGM indices were compared among low (≤0.16), medium (<0.16 to ≤0.60), and high (>0.60) GGap tertile groups. In the high GGap group, the average blood glucose was lower, while the Time Below Range <3.9 mmol/L (TBR ^<3.9 ) and <3.0 mmol/L (TBR ^<3.0 ), and low blood glucose index (LBGI) were higher than the low and middle GGap groups. Patients with minimum blood glucose levels of <3.9, <3.0 mmol/L, and TBR ^<3.9 ≥4%, and TBR ^<3.0 ≥1% had significantly higher GGap values. This is the first study to show the strong association of high GGap with CGM-based hypoglycemic indices with T2DM. To achieve diabetes treatment that effectively prevents the progression of diabetic complications, it is essential to assess the GGap of the individual patient before intensifying diabetes management.