Vitamin D levels linked with cardiovascular autonomic neuropathy in diabetes
In adults with type 1 and type 2 diabetes, both high and low levels of serum vitamin D are associated with cardiovascular autonomic neuropathy, according to an analysis of pooled patient data.
“The present findings show an inverse, U-shaped association between vitamin D level and diabetic [cardiovascular autonomic neuropathy],” Christian Stevns Hansen, MD, a PhD student in the department of clinical epidemiology at the Steno Diabetes Center in Gentofte, Denmark, and colleagues wrote. “This indicates that beneficial levels of vitamin D are restricted to a specific serum range, and both too low and too high levels are detrimental to the autonomic nervous system; however, larger observational studies are needed to confirm these findings.”
Hansen and colleagues analyzed data from 113 adults with type 1 and type 2 diabetes and no existing cardiac arrhythmia (58% men; mean age, 56 years; mean BMI, 27.6 kg/m²; mean diabetes duration, 22 years) from the outpatient clinic at the Steno Diabetes Center in Denmark between May 2013 and December 2014. Participants provided blood samples for assessment of vitamin D2 and D3, total cholesterol, HbA1c and serum creatinine. Patients were screened for cardiovascular autonomic neuropathy (CAN) using three cardiovascular reflex tests analyzed as continuous variables: deep breathing (E/I ratio), lying-to-standing (30/15 ratio) and the Valsalva maneuver, as well as an assessment of 5-minute resting heart rate and heart rate variability indices.
Within the cohort, 14% fulfilled criteria for a diagnosis of CAN; no patients had severe vitamin D deficiency; mean vitamin D level was 83.4 nmol/L. Researchers observed an inverse, U-shaped association between serum vitamin D level and E/I ratio, 30/15 ratio and the three heart rate variability indices (P < .05). After adjustment for age and sex, the vitamin D level was non-linearly associated with CAN diagnosis (P < .05). In linear regression analysis, researchers observed that an increase in vitamin D level from 25 nmol/L to 50 nmol/L was associated with an increase of 3.9% in E/I ratio (95% CI, 0.1-7.9) and 4.8% in 30/15 ratio (95% CI, 4.7-9.3). However, when vitamin D levels increased by 125 nmol/L to 150 nmol/L, researchers observed a decrease of 2.6% in E/I ratio (95% CI, –5.8-0.1) and 4.1% in 30/15 ratio (95% CI, –5.8 to –0.5).
Researchers observed no changes in outcomes associated with an increase in vitamin D levels from 85 nmol/L to 110 nmol/L; diabetes type had no modifying effect.
“Our data suggest that the association between vitamin D and CAN is mainly driven by abnormalities in the parasympathetic nervous system, given that only E/I ratio and 30/15 ratio were associated with vitamin D,” the researchers wrote. “In addition, we found vitamin D to be associated with the [heart rate variability] indices [root mean square of successive differences] and high frequency power, which also points to an effect on the parasympathetic nervous system.” –by Regina Schaffer
Disclosure: Four of the study authors are employed by the Steno Diabetes Center, a research and teaching hospital collaborating with the Danish National Health Service and owned by Novo Nordisk. One author holds shares in Novo Nordisk, another holds shares in Medicus Engineering.