Blood hemoglobin A1c levels and amyotrophic lateral sclerosis survival

Qian-Qian Wei, Yongping Chen, Bei Cao, Ru Wei Ou, Lingyu Zhang, Yanbing Hou, Xiang Gao, Huifang Shang

There are inconsistences regarding the correlation between diabetes or fasting blood glucose concentrations and the risk and survival of amyotrophic lateral sclerosis (ALS) in the previous studies. Moreover, the association between hemoglobin A1c (HbA1c) levels, which reflect long-term glycemic status, and ALS survival was not examined. A prospective cohort study including 450 Chinese sporadic ALS patients (254 men and 196 women; mean age: 55.4 y). We identified 223 deaths during average 1.6 years of follow-up. We assessed levels of fasting HbA1c (primary exposure) and glucose (secondary exposure) via ion exchange high-performance liquid chromatography and hexokinase/glucose-6-pgosphate dehydrogenase methods, respectively. Multivariate Cox proportional hazards regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of ALS mortality across the exposures. Our results indicated that, higher levels of HbA1c, but not fasting blood glucose concentrations, were significantly associated with higher risks of mortality. The adjusted HR was 1.40 (95% confidence interval (95% CI): 1.02-1.99) for HbA1c of 5.7-6.4%, and 2.06 (95% CI: 1.07-3.96) for HbA1c ≥6.5%, relative to HbA1c <5.7% (P trend =0.01), after adjustment for age, smoking, obesity, disease severity, site of onset, lifestyle, and other potential confounders. The adjusted HR was 1.38 (95% CI: 0.81-2.35, P trend =0.13) for fasting glucose concentrations ≥7.0 mmol/L vs <5.6 mmol/L. We did not observe any significant interactions between HbA1c levels and age, sex, smoking, body mass index, rate of disease progression of ALS, and site of onset (P-interactions >0.05 for all). In this prospective study, we observed that individuals with higher HbA1c levels at the baseline had higher risk of mortality, which is independent of other known risk factors.