Response of 1,5-anhydroglucitol to intensive glucose- and blood-pressure lowering interventions, and its associations with clinical outcomes in the ADVANCE trial.
Selvin E., Wang D., McEvoy JW., Juraschek SP., Lazo M., Hamet P., Cooper M., Marre M., Williams B., Harrap S., Chalmers J., Woodward M.
BACKGROUND:Low 1,5-anhydroglucitol (1,5-AG) is a marker of glycosuric hyperglycemia. We evaluated 1,5-AG with clinical outcomes and assessed the effects of glucose- and blood pressure-lowering interventions on change in 1,5-AG in type 2 diabetes. METHODS:We measured 1,5-AG in 6,826 stored samples at baseline and a random subsample of 684 participants at the 1-year follow-up visit in the ADVANCE trial. We examined baseline 1,5-AG (<6, 6-10, ≥10 ug/mL) with microvascular and macrovascular events and mortality using Cox regression models during 5 years of follow-up. Using an intention-to-treat approach, we examined 1-year change in 1,5-AG (mean and percent) in response to the glucose- and blood pressure-lowering interventions in the subsample. RESULTS:Low 1,5-AG (<6 ug/mL vs ≥10 ug/mL) was associated with microvascular events (HR 1.28, 95%CI 1.03-1.60) after adjustment for risk factors and baseline HbA1c. However, the associations for macrovascular events and mortality were not independent of HbA1c. The glucose-lowering intervention was associated with a significant 1-year increase in 1,5-AG (vs standard control) of 1.01 ug/mL (SE, 0.38), corresponding to an 8.26% (SE, 0.10) increase from baseline. We also observed an increase in 1,5-AG of similar magnitude in response to the blood pressure intervention independent of the glucose-lowering effect. CONCLUSIONS:Our results suggest that 1,5-AG is a marker of risk in adults with type 2 diabetes, but only for microvascular events independently of HbA1c. We found that 1,5-AG was improved (increased) in response to an intensive glucose-lowering intervention, although the independent effect of the blood pressure-lowering intervention on 1,5-AG suggests potential non-glycemic influences. This article is protected by copyright. All rights reserved.