Prognostic Significance of Long-term HbA<sub>1c</sub> Variability for All-Cause Mortality in the ACCORD Trial.
Pubmed ID: 32229597
Journal: Diabetes care
Publication Date: 06/01/2020
Affiliation: Shanghai Institute of Endocrine and Metabolic Diseases, Department of Endocrinology and Metabolism, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
MeSH Terms: Humans, Male, Adult, Female, Aged, Cardiovascular Diseases, Risk Factors, Middle Aged, Cause of Death, Prognosis, Follow-Up Studies, Diabetic Angiopathies, Time Factors, Diabetes Mellitus, Type 2, Blood Glucose, Hyperglycemia, Glycated Hemoglobin A, Glycemic Control
Authors: Yang Y, Cheng Y, Reaven PD, Sheng CS, Tian J, Miao Y, Bloomgarden ZT, Ning G
Cite As: Sheng CS, Tian J, Miao Y, Cheng Y, Yang Y, Reaven PD, Bloomgarden ZT, Ning G. Prognostic Significance of Long-term HbA1c Variability for All-Cause Mortality in the ACCORD Trial. Diabetes Care 2020 Jun;43(6):1185-1190. Epub 2020 Mar 30.
OBJECTIVE: The association between high glycemic variability and all-cause mortality has been widely investigated in epidemiological studies but rarely validated in glucose-lowering clinical trials. We aimed to identify the prognostic significance of visit-to-visit HbA<sub>1c</sub> variability in treated patients in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial population. RESEARCH DESIGN AND METHODS: We studied the risk of all-cause mortality in relation to long-term visit-to-visit HbA<sub>1c</sub> variability, expressed as coefficient of variation (CV), variability independent of the mean (VIM), and average real variability (ARV), from the 8th month to the transition from intensive to standard glycemic therapy. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratio (HR) and 95% CI. RESULTS: Compared with the standard therapy group (<i>n</i> = 4,728), the intensive therapy group (<i>n</i> = 4,755) had significantly lower mean HbA<sub>1c</sub> (6.6% [49 mmol/mol] vs. 7.7% [61 mmol/mol], <i>P</i> < 0.0001) and lower CV, VIM, and ARV (<i>P</i> < 0.0001). In multivariate adjusted analysis, all three HbA<sub>1c</sub> variability indices were significantly associated with total mortality in all patients as well as in the standard- and intensive-therapy groups analyzed separately. The hazard ratios for a 1-SD increase in HbA<sub>1c</sub> variability indices for all-cause mortality were 1.19 and 1.23 in intensive and standard therapy, respectively. Cross-tabulation analysis showed the third tertile of HbA<sub>1c</sub> mean and VIM had significantly higher all-cause mortality (HR 2.05; 95% CI 1.17-3.61; <i>P</i> < 0.01) only in the intensive-therapy group. CONCLUSIONS: Long-term visit-to-visit HbA<sub>1c</sub> variability was a strong predictor of all-cause mortality. HbA<sub>1c</sub> VIM combined with HbA<sub>1c</sub> mean conferred an increased risk for all-cause mortality in the intensive-therapy group.