Association between HbA1c variability and mortality in patients with type 2 diabetes.
OBJECTIVE
We aimed to evaluate the association between HbA1c variability and mortality due to all causes, cancer, and non-cancer in patients with type 2 diabetes independently of mean HbA1c levels.


METHODS
We enrolled 754 patients with type 2 diabetes who first visited our hospital between 1995 and 1996, had been followed for at least 2years, and had undergone four or more HbA1c determinations. Patients were followed through June 2012. The standard deviation (SD) or coefficient of variation (CV) was used as a measure of HbA1c variability. Risk of death was evaluated by multivariate Cox proportional hazard models.


RESULTS
Through June 2012, 63 patients died. Hazard ratios (HRs) for all-cause mortality and non-cancer mortality including cardiovascular diseases (CVD) increased across tertiles of both HbA1cSD and HbA1cCV. HRs for cancer mortality did not increase across tertiles of either HbA1cSD or HbA1cCV. Using a stepwise regression method, both HbA1cSD and HbA1cCV predicted all-cause mortality, especially non-cancer mortality. In contrast, mean HbA1c predicted cancer mortality.


CONCLUSIONS
HbA1c variability is a predictor of all-cause mortality, especially non-cancer mortality including CVD, in patients with type 2 diabetes, independent of mean HbA1c level. In contrast, mean HbA1c, but not HbA1c variability, might predict cancer mortality.
Division of Diabetes and Metabolism, The Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan. Electronic address: t-takao@asahi-life.or.jp.
Toshiko
T
Takao
Department of Biostatistics, School of Public Health, University of Tokyo, Tokyo, Japan.
Yutaka
Y
Matsuyama
Department of Public Health and Environmental Medicine, The Jikei University School of Medicine, Tokyo, Japan.
Hiroyuki
H
Yanagisawa
Division of Diabetes and Metabolism, The Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan.
Masatoshi
M
Kikuchi
Division of Diabetes and Metabolism, The Institute for Adult Diseases, Asahi Life Foundation, Tokyo, Japan.
Shoji
S
Kawazu
D000328:Adult; D000368:Aged; D002318:Cardiovascular Diseases / Q000150:complications / Q000401:mortality; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000150:complications / Q000401:mortality; D003925:Diabetic Angiopathies / Q000401:mortality; D058065:Diabetic Cardiomyopathies / Q000401:mortality; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009026:Mortality; D009369:Neoplasms / Q000150:complications / Q000401:mortality; D010044:Outpatient Clinics, Hospital; D016016:Proportional Hazards Models; D015203:Reproducibility of Results; D012189:Retrospective Studies
D006442:Glycated Hemoglobin; C517652:hemoglobin A1c protein, human
All-cause mortality; Cancer mortality; HbA1c variability; Non-cancer mortality; Type 2 diabetes