Jonas Ghouse1,2, Morten W Skov1,2, Jørgen K Kanters3, Bent Lind4, Jonas L Isaksen3,5, Paul Blanche6, Stig Haunsø1,2, Lars Køber7,8, Jesper H Svendsen1,2,7,8, Morten S Olesen1,2, Anders G Holst1, Thomas A Gerds6, Jonas B Nielsen9,10. 1. Laboratory of Molecular Cardiology, Department of Cardiology, Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 2. Laboratory of Molecular Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. 3. Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark. 4. Department of Clinical Biochemistry, Copenhagen University Hospital, Hvidovre, Denmark. 5. Department of Health Science and Technology, Aalborg University, Aalborg, Denmark. 6. Section of Biostatistics, University of Copenhagen, Copenhagen, Denmark. 7. Department of Cardiology, Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. 8. Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. 9. Laboratory of Molecular Cardiology, Department of Cardiology, Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark jonas.bille.nielsen@gmail.com. 10. Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, MI.
Abstract
OBJECTIVE: We aimed to study whether visit-to-visit variability of glycated hemoglobin A1c (HbA1c) is associated with incident major adverse cardiovascular events (MACE), all-cause mortality, and type 2 diabetes in people without diabetes. RESEARCH DESIGN AND METHODS: We included primary care patients with no history of diabetes or cardiovascular disease and with three annual HbA1c measurements within normal range (<6.5% [48 mmol/mol]). For each individual, we measured the HbA1c variability as the SD of the residuals obtained from a linear regression on the three HbA1c measurements. From the linear regression, we also obtained the estimated index HbA1c (intercept) and the trend over time (slope). Follow-up began at the date of the third measurement. Associations between HbA1c variability and outcome were analyzed using Cox regression, adjusted for traditional risk factors, intercept, and trend and reported as hazard ratio per SD increase in variability (HRSD). RESULTS: In total, 6,756 individuals were included. During a median follow-up time of 6.3 years, 996 developed MACE, 856 died, and 1,267 developed type 2 diabetes. We found a significant association between increasing HbA1c variability and incident MACE (HRSD 1.09 [95% CI 1.03-1.15]) and all-cause mortality (HRSD 1.13 [95% CI 1.07-1.20]), whereas there were no associations with type 2 diabetes (HRSD 1.00 [95% CI 0.95-1.05]). We calculated 5-year absolute risks of MACE and all-cause mortality and found clinically relevant differences across several age, sex, comorbidity, and HbA1c variability-defined subgroups. CONCLUSIONS: In a primary care population free of diabetes and cardiovascular disease, high HbA1c variability was associated with increased risks of MACE and all-cause mortality.
OBJECTIVE: We aimed to study whether visit-to-visit variability of glycated hemoglobin A1c (HbA1c) is associated with incident major adverse cardiovascular events (MACE), all-cause mortality, and type 2 diabetes in people without diabetes. RESEARCH DESIGN AND METHODS: We included primary care patients with no history of diabetes or cardiovascular disease and with three annual HbA1c measurements within normal range (<6.5% [48 mmol/mol]). For each individual, we measured the HbA1c variability as the SD of the residuals obtained from a linear regression on the three HbA1c measurements. From the linear regression, we also obtained the estimated index HbA1c (intercept) and the trend over time (slope). Follow-up began at the date of the third measurement. Associations between HbA1c variability and outcome were analyzed using Cox regression, adjusted for traditional risk factors, intercept, and trend and reported as hazard ratio per SD increase in variability (HRSD). RESULTS: In total, 6,756 individuals were included. During a median follow-up time of 6.3 years, 996 developed MACE, 856 died, and 1,267 developed type 2 diabetes. We found a significant association between increasing HbA1c variability and incident MACE (HRSD 1.09 [95% CI 1.03-1.15]) and all-cause mortality (HRSD 1.13 [95% CI 1.07-1.20]), whereas there were no associations with type 2 diabetes (HRSD 1.00 [95% CI 0.95-1.05]). We calculated 5-year absolute risks of MACE and all-cause mortality and found clinically relevant differences across several age, sex, comorbidity, and HbA1c variability-defined subgroups. CONCLUSIONS: In a primary care population free of diabetes and cardiovascular disease, high HbA1c variability was associated with increased risks of MACE and all-cause mortality.
Authors: Justin B Echouffo-Tcheugui; Songzhu Zhao; Guy Brock; Roland A Matsouaka; David Kline; Joshua J Joseph Journal: Diabetes Care Date: 2019-01-18 Impact factor: 19.112
Authors: Yun Shen; Jian Zhou; Lizheng Shi; Elizabeth Nauman; Peter T Katzmarzyk; Eboni G Price-Haywood; Ronald Horswell; Alessandra N Bazzano; Somesh Nigam; Gang Hu Journal: Diabetes Obes Metab Date: 2020-10-07 Impact factor: 6.577
Authors: Michael P Bancks; April P Carson; Cora E Lewis; Erica P Gunderson; Jared P Reis; Pamela J Schreiner; Yuichiro Yano; Mercedes R Carnethon Journal: Diabetologia Date: 2019-05-22 Impact factor: 10.122