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 Obes Metab. 2019 Aug;21(8):2017-2023. doi: 10.1111/dom.13755. Epub 2019 May 29.


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.

Keywords: clinical trial; cohort study; diabetes complications; glycaemic control; randomized trial; type 2 diabetes.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antihypertensive Agents / administration & dosage*
  • Blood Glucose / drug effects
  • Deoxyglucose / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Drug Therapy, Combination
  • Female
  • Gliclazide / administration & dosage
  • Glycated Hemoglobin A / drug effects
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypoglycemic Agents / administration & dosage*
  • Indapamide / administration & dosage
  • Intention to Treat Analysis
  • Male
  • Microvessels / drug effects
  • Middle Aged
  • Perindopril / administration & dosage
  • Proportional Hazards Models
  • Risk Factors
  • Treatment Outcome


  • Antihypertensive Agents
  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • hemoglobin A1c protein, human
  • 1,5-anhydroglucitol
  • Deoxyglucose
  • Indapamide
  • Gliclazide
  • Perindopril