September 02, 2016
2 min read

Vitamin B12 level associated with cardiovascular autonomic neuropathy in type 2 diabetes

You've successfully added to your alerts. You will receive an email when new content is published.

Click Here to Manage Email Alerts

We were unable to process your request. Please try again later. If you continue to have this issue please contact

Adults with type 2 diabetes who have low levels of vitamin B12 are more likely to develop cardiovascular autonomic neuropathy vs. those with higher B12 levels, recent findings suggest.

Christian S. Hansen, MD, of the department of clinical epidemiology at the Steno Diabetes Center in Gentofte, Denmark, and colleagues analyzed data from 469 patients with type 2 diabetes screened for cardiovascular autonomic neuropathy (CAN) using three CV reflex tests, 5-minute resting heart rate and heart rate variability indices between June 2013 and December 2014 (mean age, 59 years; 63% men; mean diabetes duration, 10 years). Participants provided blood samples for serum vitamin B12 measurements and underwent vibration sensation testing to assess peripheral neuropathy. Researchers used linear regression analysis to determine cross-sectional associations between vitamin B12 as a determinant and measures of neuropathy as outcomes.

Within the cohort, 13.4% had CAN; 11.3% had reduced vibration detection threshold. Mean serum vitamin B12 level was 289 pmol/L; 0.6% had vitamin B12 deficiency (125 pmol/L or less); 35.4% had borderline vitamin B12 deficiency (between 125 and 250 pmol/L). Mean vitamin B12 levels were lower among patients treated with either proton pump inhibitors only (mean B12 level, 235.5 pmol/L), metformin only (280 pmol/L) or both (262 pmol/L) vs. patients treated with neither drug (365.5 pmol/L).

“The present study presents evidence that patients with type 2 diabetes who are treated with metformin and [proton pump inhibitors] have lower serum levels of vitamin B12 than patients not treated with these drugs,” the researchers wrote. “These findings support a growing amount of evidence that these drug therapies are a cause of vitamin B12 deficiency.”

Researchers found that vitamin B12 levels were associated with lower OR for the diagnosis of CAN (P = .04). A 25 pmol/L higher level of vitamin B12 was associated with an OR for CAN diagnosis of 0.94 (95% CI, 0.88-1) in models adjusted for age, sex, diabetes duration and alcohol consumption. A 25 pmol/L higher level of vitamin B12 was also associated with a 21% increase in CV autonomic reflex test for deep breathing (E/I ratio; 95% CI, 0.01-0.41) and a decrease in 5-minute resting heart rate of 0.25 beats per minute (95% CI, 0.47-0.04).

Results persisted after excluding patients receiving B12 supplementation, and adjusting for HbA1c, total cholesterol, triglyceride levels, systolic blood pressure and smoking status, according to researchers.

“However, when adjusting for the use of beta-blockers, diuretics and tricyclic antidepressants in addition to the mentioned confounders in model 4, only the CAN diagnosis, E/I ratio and the LF/HF ratio were significantly associated with vitamin B12,” the researchers wrote. –by Regina Schaffer

Disclosure: The Steno Diabetes Center is owned by Novo Nordisk; two of the study authors hold shares in Novo Nordisk; one holds shares in Medicus Engineering.


AUTHORS: Hansen CS, Jensen JS, Ridderstrale M, Vistisen D, Jorgensen ME, Fleischer J

BACKGROUND: Vitamin B12 deficiency could be associated with cardiovascular autonomic neuropathy (CAN) in diabetes patients. We aim to investigate the association between serum levels of vitamin B12 and CAN in type 2 diabetes patients ...