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-Elizondo, Pavel Hamet, Mark E. Cooper, Michel Marre, Bryan Williams, Stephen Harrap, John Chalmers, Mark Woodward

Research output: Contribution to journalArticle

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 (US)
JournalDiabetes, Obesity and Metabolism
DOIs
StatePublished - Jan 1 2019

Fingerprint

Blood Pressure
Glucose
Type 2 Diabetes Mellitus
1,5-anhydroglucitol
Mortality
Glycosylated Hemoglobin A
Proportional Hazards Models
Confidence Intervals

Keywords

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

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Response of 1,5-anhydroglucitol level to intensive glucose- and blood-pressure lowering interventions, and its associations with clinical outcomes in the ADVANCE trial. / Selvin, Elizabeth; Wang, Dan; McEvoy, John William; Juraschek, Stephen P.; Lazo-Elizondo, Mariana; Hamet, Pavel; Cooper, Mark E.; Marre, Michel; Williams, Bryan; Harrap, Stephen; Chalmers, John; Woodward, Mark.

In: Diabetes, Obesity and Metabolism, 01.01.2019.

Research output: Contribution to journalArticle

Selvin, Elizabeth ; Wang, Dan ; McEvoy, John William ; Juraschek, Stephen P. ; Lazo-Elizondo, Mariana ; Hamet, Pavel ; Cooper, Mark E. ; Marre, Michel ; Williams, Bryan ; Harrap, Stephen ; Chalmers, John ; Woodward, Mark. / Response of 1,5-anhydroglucitol level to intensive glucose- and blood-pressure lowering interventions, and its associations with clinical outcomes in the ADVANCE trial. In: Diabetes, Obesity and Metabolism. 2019.
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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.",
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author = "Elizabeth Selvin and Dan Wang and McEvoy, {John William} and Juraschek, {Stephen P.} and Mariana Lazo-Elizondo and Pavel Hamet and Cooper, {Mark E.} and Michel Marre and Bryan Williams and Stephen Harrap and John Chalmers and Mark Woodward",
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AU - Selvin, Elizabeth

AU - Wang, Dan

AU - McEvoy, John William

AU - Juraschek, Stephen P.

AU - Lazo-Elizondo, Mariana

AU - Hamet, Pavel

AU - Cooper, Mark E.

AU - Marre, Michel

AU - Williams, Bryan

AU - Harrap, Stephen

AU - Chalmers, John

AU - Woodward, Mark

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Y1 - 2019/1/1

N2 - 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.

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