Proximal HbA1C Level and First Hypoglycemia Hospitalization in Adults with Incident Type 2 Diabetes

Context: HbA1C is an important predictor of severe hypoglycemia.

Objective: To determine the association of proximal HbA1C level with first hypoglycemia requiring hospitalization (HH) in adults with incident type 2 diabetes (T2D).

Design, Setting, and Participants: A nested case-control study was designed using linked data from the Clinical Practice Research Datalink and Hospital Episode Statistics in England in 1997-2014. The first hypoglycemia as primary diagnosis for hospitalization after T2D diagnosis was identified. Proximal HbA1C was measured within 90 days prior to the first HH.

Main Outcome Measure: Odds ratio (OR) for developing HH.

Results: The association of proximal HbA1C level with first HH was similar between HbA1C of 6.0% (OR 1.54; 95% CI 1.12-2.11) and 9.0% (1.48 [1.01-2.17]), compared to the reference HbA1C level of 7.0%. For proximal HbA1C level of 4.0-6.5%, every additional 0.5% increase in HbA1C was associated with lower first HH risk with OR (95% CI) ranging between 0.37 (0.20-0.67) and 0.86 (0.76-0.98). For proximal HbA1C level of 8.0-11.5%, every additional 0.5% increase in HbA1C was associated with higher first HH risk with OR (95% CI) ranging between 1.16 (1.04-1.29) and 1.34 (1.18-1.52). The U-shaped association between proximal HbA1C level and first HH did not exist among current sulfonylureas users but persisted among current insulin users (Pinteraction=0.002). Among current non-insulin non-sulfonylureas users who had first HH, 78% took insulin or sulfonylureas prior to HH.

Conclusions: Having either poor or near-normal HbA1C was associated with higher risk of first HH in T2D within three months.