TY - JOUR
T1 - Response of 1,5-anhydroglucitol level to intensive glucose- and blood-pressure lowering interventions, and its associations with clinical outcomes in the ADVANCE trial
AU - Selvin, Elizabeth
AU - Wang, Dan
AU - McEvoy, John William
AU - Juraschek, Stephen P.
AU - Lazo, Mariana
AU - Hamet, Pavel
AU - Cooper, Mark E.
AU - Marre, Michel
AU - Williams, Bryan
AU - Harrap, Stephen
AU - Chalmers, John
AU - Woodward, Mark
N1 - Funding Information:
The ADVANCE trial was funded by grants from the National Health and Medical Research Council (NHMRC) of Australia and Servier Laboratories. This study was supported by National Institutes of Health (NIH), National Institute of Diabetes and Digestive and Kidney Diseases grant R01 DK108784 to E.S. S.P.J. was supported by NIH/NHLBI grants K23 HL135273 and R21 HL144876. J.C. and M.W. are supported by a NHMRC programme grant and M.W. also has a NHMRC Principal Research Fellowship
Publisher Copyright:
© 2019 John Wiley & Sons Ltd
PY - 2019/8
Y1 - 2019/8
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.
AB - 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.
KW - clinical trial
KW - cohort study
KW - diabetes complications
KW - glycaemic control
KW - randomized trial
KW - type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85066487602&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85066487602&partnerID=8YFLogxK
U2 - 10.1111/dom.13755
DO - 10.1111/dom.13755
M3 - Article
C2 - 31050156
AN - SCOPUS:85066487602
VL - 21
SP - 2017
EP - 2023
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
SN - 1462-8902
IS - 8
ER -