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

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. K E Y W O R D Sclinical trial, diabetes complications, glycaemic control, randomized trial, type 2 diabetes, cohort study

Observational analyses from ADVANCE and ADVANCE‐ON

“…Mean (with standard error) of 1,5‐anhydroglucitol (1,5‐AG) at baseline and after 1 year, in (A) glucose treatment arm and (B) blood pressure treatment arm in ADVANCE. Figure is as appears in Selvin et al (2019) …”

“…Additionally, the same amount was stored for a random sample of 1000 patients at the 1‐year clinic visit. This was in order to account for regression dilution when analysing associations, although it is also useful for assessing changes in biomarkers according to the randomized intervention …”

“…As this study started after ADVANCE‐ON terminated, case numbers were enhanced compared to the earlier blood substudies. To date, only one paper has appeared from this substudy; this paper considered both the impact of the blood pressure and glucose interventions on 1,5‐anhydroglucitol and the effect of 1,5‐anhydroglucitol on CVD outcomes (Figure ) . Similar papers, with such dual aims, are planned.…”

“…This was in order to account for regression dilution when analysing associations, 57 although it is also useful for assessing changes in biomarkers according to the randomized intervention. 58 The 20 mL collected was split into two tubes, one with an EDTA additive and one with heparin. The specimens were spun for 10 minutes in a centrifuge and then the plasma and buffy coat layers were immediately pipetted into microtubes.…”

Serum 1,5-Anhydroglucitol to Glycated Albumin Ratio Can Help Early Distinguish Fulminant Type 1 Diabetes Mellitus from Newly Onset Type 1A Diabetes Mellitus

“…1,5-Anhydroglucitol (1,5-AG) has recently attracted extensive attention worldwide because it represents the average glucose of the past 1 to 2 weeks in diabetic patients and has some advantages in reflecting glucose fluctuations and postprandial hyperglycemia when compared with HbA 1c [5][6][7]. Several studies have shown that 1,5-AG is stable in vivo and decreases with increasing glucose level.…”