Vitamin B12 deficiency is associated with cardiovascular autonomic neuropathy in patients with type 2 diabetes

J Diabetes Complications. 2017 Jan;31(1):202-208. doi: 10.1016/j.jdiacomp.2016.08.025. Epub 2016 Aug 30.

Abstract

Aims: 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.

Methods: 469 ambulatory type 2 diabetes patients (mean diabetes duration 10.0years (IQR 5.0;17.0), mean age 59.0years (SD 11.6), 63% men, mean B12 289.0pmol/l (IQR 217;390)) were screened for CAN using three cardiovascular reflex tests, five minute resting heart rate (5min RHR) and heart rate variability indices.

Results: Serum levels of vitamin B12 were significantly lower in patients treated with metformin and/or proton pump inhibitors (PPIs) compared with patients not treated (p<0.001). A 25pmol/l higher level of vitamin B12 was associated with an odds ratio of the CAN diagnosis of 0.94 (95% CI 0.88; 1.00, p=0.034), an increase in E/I-ratio of 0.21% (95% CI 0.01; 0.43, p=0.038), and a decrease in 5min RHR of 0.25 beats per minute (95% CI -0.47; -0.03, p=0.025).

Conclusion: Vitamin B12 may be inversely associated with CAN in patients with type 2 diabetes. Confirmatory studies investigating a causal role of vitamin B12 for the development of diabetic CAN are warranted.

Keywords: Cardiovascular autonomic neuropathy; Complications; Metformin; Proton pump inhibitors; Type 2 diabetes; Vitamin B12.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antihypertensive Agents / therapeutic use
  • Autonomic Nervous System Diseases / complications*
  • Autonomic Nervous System Diseases / epidemiology
  • Cardiovascular Diseases / complications*
  • Cardiovascular Diseases / epidemiology
  • Cohort Studies
  • Cross-Sectional Studies
  • Denmark / epidemiology
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetic Angiopathies / complications
  • Diabetic Angiopathies / drug therapy
  • Diabetic Angiopathies / epidemiology
  • Diabetic Cardiomyopathies / complications*
  • Diabetic Cardiomyopathies / epidemiology
  • Diabetic Neuropathies / complications*
  • Diabetic Neuropathies / epidemiology
  • Female
  • Heart Rate / drug effects
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Mass Screening
  • Metformin / therapeutic use
  • Middle Aged
  • Prevalence
  • Proton Pump Inhibitors / therapeutic use
  • Risk Factors
  • Vitamin B 12 / blood
  • Vitamin B 12 Deficiency / complications*

Substances

  • Antihypertensive Agents
  • Hypoglycemic Agents
  • Proton Pump Inhibitors
  • Metformin
  • Vitamin B 12