title: Vitamin B12 deficiency is associated with cardiovascular autonomic neuropathy in patients with type 2 diabetes.
abstract: 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.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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.
authors.affiliation: Department of Clinical Epidemiology, Steno Diabetes Center A/S, Gentofte, Denmark. Electronic address: csvh@steno.dk.
authors.forename: Christian S
authors.initials: CS
authors.lastname: Hansen
authors.affiliation: Department of Cardiology, Gentofte Hospital, Gentofte, Denmark.
authors.forename: Jan S
authors.initials: JS
authors.lastname: Jensen
authors.affiliation: Steno Diabetes Center A/S, Gentofte, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Ridderstråle
authors.affiliation: Department of Clinical Epidemiology, Steno Diabetes Center A/S, Gentofte, Denmark.
authors.forename: Dorte
authors.initials: D
authors.lastname: Vistisen
authors.affiliation: Department of Clinical Epidemiology, Steno Diabetes Center A/S, Gentofte, Denmark.
authors.forename: Marit E
authors.initials: ME
authors.lastname: Jørgensen
authors.affiliation: Medical Research Laboratories, Clinical Institute of Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Jesper
authors.initials: J
authors.lastname: Fleischer
mesh_terms: D000959:Antihypertensive Agents / Q000627:therapeutic use; D001342:Autonomic Nervous System Diseases / Q000150:complications* / Q000453:epidemiology; D002318:Cardiovascular Diseases / Q000150:complications* / Q000453:epidemiology; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D003718:Denmark / Q000453:epidemiology; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications* / Q000188:drug therapy; D003925:Diabetic Angiopathies / Q000150:complications / Q000188:drug therapy / Q000453:epidemiology; D058065:Diabetic Cardiomyopathies / Q000150:complications* / Q000453:epidemiology; D003929:Diabetic Neuropathies / Q000150:complications* / Q000453:epidemiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008403:Mass Screening; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D015995:Prevalence; D054328:Proton Pump Inhibitors / Q000627:therapeutic use; D012307:Risk Factors; D014805:Vitamin B 12 / Q000097:blood; D014806:Vitamin B 12 Deficiency / Q000150:complications*
chemical_list: D000959:Antihypertensive Agents; D007004:Hypoglycemic Agents; D054328:Proton Pump Inhibitors; D008687:Metformin; D014805:Vitamin B 12
keywords: Cardiovascular autonomic neuropathy; Complications; Metformin; Proton pump inhibitors; Type 2 diabetes; Vitamin B12