Response of 1,5-anhydroglucitol level to intensive glucose- and blood-pressure lowering interventions, and its associations with clinical outcomes in the ADVANCE trial

Elizabeth Selvin, Dan Wang, John William McEvoy, Stephen P. Juraschek, Mariana Lazo, Pavel Hamet, Mark E. Cooper, Michel Marre, Bryan Williams, Stephen Harrap, John Chalmers, Mark Woodward

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Abstract

Aims: To evaluate 1,5-anhydroglucitol (1,5-AG) according to clinical outcomes and assess the effects of glucose- and blood pressure-lowering interventions on change in 1,5-AG levels in people with type 2 diabetes. Methods: We measured 1,5-AG in 6826 stored samples at baseline and in a random subsample of 684 participants at the 1-year follow-up visit in the ADVANCE trial. We examined baseline 1,5-AG [< 39.7, 39.7-66.2, ≥ 66.2 μmol/L (<6, 6-10, ≥10 μg/mL)] and 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 level [<39.7 μmol/L vs ≥ 66.2 μmol/L (<6 μg/mL vs ≥10 μg/mL)] was associated with microvascular events (hazard ratio 1.28, 95% confidence interval 1.03-1.60) after adjustment for risk factors and baseline glycated haemoglobin (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 6.69 μmol/L (SE 2.52) [1.01 μg/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-glycaemic influences.

Original languageEnglish
Pages (from-to)2017-2023
Number of pages7
JournalDiabetes, Obesity and Metabolism
Volume21
Issue number8
DOIs
Publication statusPublished - Aug 2019
Externally publishedYes

Keywords

  • clinical trial
  • cohort study
  • diabetes complications
  • glycaemic control
  • randomized trial
  • type 2 diabetes

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    Selvin, E., Wang, D., McEvoy, J. W., Juraschek, S. P., Lazo, M., Hamet, P., Cooper, M. E., Marre, M., Williams, B., Harrap, S., Chalmers, J., & Woodward, M. (2019). Response of 1,5-anhydroglucitol level to intensive glucose- and blood-pressure lowering interventions, and its associations with clinical outcomes in the ADVANCE trial. Diabetes, Obesity and Metabolism, 21(8), 2017-2023. https://doi.org/10.1111/dom.13755