Association between HbA1c variability and mortality in patients with type 2 diabetes.

AIMS 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.

[1]  Y. Arabi,et al.  Glycaemic Fluctuation Predicts Mortality in Critically Ill Patients , 2010, Anaesthesia and intensive care.

[2]  C. Hsieh,et al.  Acute and chronic fluctuations in blood glucose levels can increase oxidative stress in type 2 diabetes mellitus , 2012, Acta Diabetologica.

[3]  E. Bonora,et al.  Fasting plasma glucose variability predicts 10-year survival of type 2 diabetic patients: the Verona Diabetes Study. , 2000, Diabetes care.

[4]  E. Bonora,et al.  Variability of body weight, pulse pressure and glycaemia strongly predict total mortality in elderly type 2 diabetic patients. The Verona Diabetes Study , 2008, Diabetes/metabolism research and reviews.

[5]  J. Krinsley,et al.  Glycemic variability: A strong independent predictor of mortality in critically ill patients* , 2008, Critical care medicine.

[6]  Michael E. Miller,et al.  The association between symptomatic, severe hypoglycaemia and mortality in type 2 diabetes: retrospective epidemiological analysis of the ACCORD study , 2010, BMJ : British Medical Journal.

[7]  Diederick Grobbee,et al.  Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. , 2008, The New England journal of medicine.

[8]  K. Lu,et al.  Variability in hemoglobin A1c predicts all-cause mortality in patients with type 2 diabetes. , 2012, Journal of diabetes and its complications.

[9]  Yasuhiko Tomino,et al.  Revised equations for estimated GFR from serum creatinine in Japan. , 2009, American journal of kidney diseases : the official journal of the National Kidney Foundation.

[10]  R. de Marco,et al.  Long-term instability of fasting plasma glucose, a novel predictor of cardiovascular mortality in elderly patients with non-insulin-dependent diabetes mellitus: the Verona Diabetes Study. , 1997, Circulation.

[11]  F. T. E. Group,et al.  Low transition rate from normo- and low microalbuminuria to proteinuria in Japanese type 2 diabetic individuals: the Japan Diabetes Complications Study (JDCS) , 2011, Diabetologia.

[12]  E. Bonora,et al.  Long-term instability of fasting plasma glucose predicts mortality in elderly NIDDM patients: the Verona Diabetes Study , 1995, Diabetologia.

[13]  R. Holman,et al.  10-year follow-up of intensive glucose control in type 2 diabetes. , 2008, The New England journal of medicine.

[14]  D. Owens,et al.  Regulation of oxidative stress by glycaemic control: evidence for an independent inhibitory effect of insulin therapy , 2009, Diabetologia.

[15]  Y. Ohashi,et al.  Comparison of Various Lipid Variables as Predictors of Coronary Heart Disease in Japanese Men and Women With Type 2 Diabetes , 2012, Diabetes Care.

[16]  Hanqing Cao,et al.  Blood Glucose Variability is Associated with Mortality in the Surgical Intensive Care Unit , 2008, The American surgeon.

[17]  R. Holman,et al.  Non-HDL cholesterol is less informative than the total-to-HDL cholesterol ratio in predicting cardiovascular risk in type 2 diabetes. , 2005, Diabetes care.

[18]  P. Dandona,et al.  Insulin Suppresses Endotoxin-Induced Oxidative, Nitrosative, and Inflammatory Stress in Humans , 2010, Diabetes Care.

[19]  Jean-Paul Cristol,et al.  Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. , 2006, JAMA.

[20]  B. Zinman,et al.  Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. , 2005, The New England journal of medicine.

[21]  Grant D. Huang,et al.  Glucose control and vascular complications in veterans with type 2 diabetes. , 2009, The New England journal of medicine.

[22]  岩本 安彦,et al.  アンケート調査による日本人糖尿病の死因 : 1991-2000年の10年間, 18,385名での検討 , 2007 .

[23]  Michael E. Miller,et al.  Effects of intensive glucose lowering in type 2 diabetes. , 2008, The New England journal of medicine.

[24]  Rinaldo Bellomo,et al.  Variability of Blood Glucose Concentration and Short-term Mortality in Critically Ill Patients , 2006, Anesthesiology.

[25]  Hiroyuki Yanagisawa,et al.  [Influence of plasma glucose variability and age on onset of diabetic retinopathy in diabetic patients analysis of results of long-term outpatient follow-up for 30 years or more]. , 2009, Nihon Ronen Igakkai zasshi. Japanese journal of geriatrics.

[26]  Nader Rifai,et al.  Non-HDL cholesterol and apolipoprotein B predict cardiovascular disease events among men with type 2 diabetes. , 2004, Diabetes care.

[27]  Hiroshi Ito,et al.  International clinical harmonization of glycated hemoglobin in Japan: From Japan Diabetes Society to National Glycohemoglobin Standardization Program values , 2012, Journal of diabetes investigation.