TY - JOUR
T1 - Changes in albuminuria and the risk of major clinical outcomes in diabetes
T2 - Results from ADVANCE-ON
AU - Jun, Min
AU - Ohkuma, Toshiaki
AU - Zoungas, Sophia
AU - Colagiuri, Stephen
AU - Mancia, Giuseppe
AU - Marre, Michel
AU - Matthews, David
AU - Poulter, Neil
AU - Williams, Bryan
AU - Rodgers, Anthony
AU - Perkovic, Vlado
AU - Chalmers, John
AU - Woodward, Mark
N1 - Funding Information:
Funding. The ADVANCE trial was funded by grants from the National Health and Medical Research Council of Australia and Servier Laboratories. M.J. was supported by postdoctoral fellowships from the Canadian Institutes of Health Research and Alberta Innovates: Health Solutions and an early career fellowship from the National Health and Medical Research Council of Australia. T.O. holds the Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad. N.P. received research grants from Diabetes UK, British Heart Foundation, and the Health Technology Assessment Program. J.C. received research grants from the National Health and Medical Research Council of Australia for the ADVANCE trial and ADVANCE-ON posttrial follow-up. M.W. is a National Health and Medical Research Council of Australia Principal Research Fellow (1080206). Duality of Interest. S.Z. reports past participation in advisory boards and/or receiving honoraria from Amgen Australia, AstraZeneca/Bristol-Myers Squibb Australia, Janssen-Cilag, Merck Sharp & Dohme (Australia), Novartis Australia, Sanofi, Servier Laboratories, and Takeda Pharmaceutical Company Australia. S.C. reports receiving fees for serving on advisory boards and lecture fees from Servier Laboratories. G.M. reports personal fees from Servier Laboratories, Bayer, Boehringer Ingelheim, Daiichi Sankyo, Medtronic, Novartis, Menarini Group, Recordati, and Takeda Pharmaceutical Company. M.M. received personal fees from Novo Nordisk, Sanofi, Eli Lilly and Company, Merck Sharp & Dohme, Abbott, Novartis, Servier Laboratories, and AstraZeneca and grant support from Novo Nordisk, Sanofi, Eli Lilly and Company, Merck Sharp & Dohme, and Novartis. D.M. has received personal fees from Servier Laboratories. N.P. received honoraria from Servier Laboratories, Takeda Pharmaceutical Company, Menarini Group, and Pfizer; grant support from Servier Laboratories and Pfizer; and personal fees from Servier Laboratories, Takeda Pharmaceutical Company, Menarini Group, and Pfizer. B.W. reports personal fees from Servier Laboratories, Novartis, Boehringer Ingelheim, and Merck Sharp & Dohme. A.R. receives salary in part from George Health Enterprises, the social enterprise arm of The George Institute for Global Health (George Health Enterprises has received investment to develop fixed-dose combinations containing aspirin, statin, and BP-lowering drugs). V.P. reports honoraria for scientific lectures from Boehringer Ingelheim, Merck Sharp & Dohme, AbbVie, Roche, AstraZeneca, and Servier Laboratories and serves on steering committees and/or advisory boards supported by AbbVie, Astellas Pharma, Baxter, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Janssen, and Pfizer. J.C. received research grants from Servier Laboratories for the ADVANCE trial and ADVANCE-ON posttrial follow-up and honoraria for speaking about these studies at scientific meetings. M.W. reports consultancy fees from Am-gen. No other potential conflicts of interest relevant to this article were reported. Author Contributions. M.J., T.O., J.C., and M.W. contributed to the concept and rationale for the study and interpretation of the results and drafted the manuscript. M.J. and T.O. conducted statistical analysis with advice from M.W. M.J., T.O., S.Z., S.C., G.M., M.M., D.M., N.P., B.W., A.R., V.P., J.C., and M.W. contributed to discussion and reviewed and edited the manuscript. M.W. and J.C. are the guarantors of this work and, as such, had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Publisher Copyright:
© 2017 by the American Diabetes Association.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - OBJECTIVE To assess the association between 2-year changes in urine albumin-to-creatinine ratio (UACR) and the risk of clinical outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS We analyzed data from 8,766 participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Post-Trial Observational Study (ADVANCE-ON). Change in UACR was calculated from UACR measurements 2 years apart, classified into three groups: Decrease in UACR of ≥30%, minor change, and increase in UACR of ≥30%. By analyzing changes from baseline UACR groups, categorized into thirds, we repeated these analyses accounting for regression to the mean (RtM). The primary outcome was the composite of major macrovascular events, renal events, and all-cause mortality; secondary outcomes were these components. Cox regression models were used to estimate hazard ratios (HRs). RESULTS Over a median follow-up of 7.7 years, 2,191 primary outcomes were observed. Increases in UACR over 2 years independently predicted a greater risk of the primary outcome (HR for ≥30% UACR increase vs. minor change: 1.26; 95% CI 1.13-1.41), whereas a decrease inUACRwas not significantly associatedwith lower risk (HR 0.93; 95% CI 0.83-1.04). However, after allowing for RtM, the effect of "real" decrease in UACR on the primary outcome was found to be significant (HR 0.84; 95% CI 0.75- 0.94), whereas the estimated effect on an increase was unchanged. CONCLUSIONS Changes in UACR predicted changes in the risk of major clinical outcomes and mortality in type 2 diabetes, supporting the prognostic utility of monitoring albuminuria change over time.
AB - OBJECTIVE To assess the association between 2-year changes in urine albumin-to-creatinine ratio (UACR) and the risk of clinical outcomes in type 2 diabetes. RESEARCH DESIGN AND METHODS We analyzed data from 8,766 participants in the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation Post-Trial Observational Study (ADVANCE-ON). Change in UACR was calculated from UACR measurements 2 years apart, classified into three groups: Decrease in UACR of ≥30%, minor change, and increase in UACR of ≥30%. By analyzing changes from baseline UACR groups, categorized into thirds, we repeated these analyses accounting for regression to the mean (RtM). The primary outcome was the composite of major macrovascular events, renal events, and all-cause mortality; secondary outcomes were these components. Cox regression models were used to estimate hazard ratios (HRs). RESULTS Over a median follow-up of 7.7 years, 2,191 primary outcomes were observed. Increases in UACR over 2 years independently predicted a greater risk of the primary outcome (HR for ≥30% UACR increase vs. minor change: 1.26; 95% CI 1.13-1.41), whereas a decrease inUACRwas not significantly associatedwith lower risk (HR 0.93; 95% CI 0.83-1.04). However, after allowing for RtM, the effect of "real" decrease in UACR on the primary outcome was found to be significant (HR 0.84; 95% CI 0.75- 0.94), whereas the estimated effect on an increase was unchanged. CONCLUSIONS Changes in UACR predicted changes in the risk of major clinical outcomes and mortality in type 2 diabetes, supporting the prognostic utility of monitoring albuminuria change over time.
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U2 - 10.2337/dc17-1467
DO - 10.2337/dc17-1467
M3 - Article
C2 - 29079715
AN - SCOPUS:85038956242
SN - 1935-5548
VL - 41
SP - 163
EP - 170
JO - Diabetes Care
JF - Diabetes Care
IS - 1
ER -
