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Low or High Vitamin D and Cardiovascular Autonomic Neuropathy

New study finds adults with diabetes who have either high or low vitamin D levels could have an increased risk of cardiovascular autonomic neuropathy (CAN).

Cardiovascular autonomic function refers to the involuntary functions of the heart, such as controlling heart rate and blood pressure. People with type 2 diabetes are at an increased risk for compromised cardiovascular autonomic function, since chronically high blood glucose can result in damage to the nerves that are responsible for autonomic function.

Another common symptom experienced in type 2 diabetes is peripheral neuropathy. Peripheral neuropathy is damage to the nerves of the peripheral nervous system, which is the network of nerves that carry information from the brain and spinal cord to the rest of the body. Cardiovascular autonomic neuropathy is a type of peripheral neuropathy that refers to the damage of autonomic nerves, which control the heart and blood vessels.

There are many aspects of cardiovascular autonomic neuropathy that hint at a role for vitamin D. Vitamin D, overall, is associated with diabetes and cardiovascular health. More specifically, vitamin D has been shown to help regulate blood pressure and aid the pumping and contracting of the heart. Cardiovascular autonomic neuropathy can cause irregular heart rate, low blood pressure, exercise intolerance, and an increased risk for mortality.

Cardiovascular autonomic neuropathy occurs when the nerves that control heart rate become damaged, which can cause the heart rate to stay high even during rest and also result in lower blood pressure.

Researchers at the Steno Diabetes Centre, Gentofte, analyzed data from 113 adults with type 1 and type 2 diabetes, none of whom had existing cardiac arrhythmia.  Blood samples were measured from vitamin D2 and D3, total cholesterol and HbA1c, and patients were screened for CAN using cardiovascular reflex tests.

The study team observed an “inverse, U-shaped association between vitamin D level and diabetic (CAN)” that indicates “both too low and too high levels [of vitamin D] are detrimental to the autonomic nervous system.”

Also, they discovered that the type of diabetes had no modifying effect, and the association remained after adjustment for age and sex.

The data suggested that the “association between vitamin D and CAN is mainly driven by abnormalities in the parasympathetic nervous system, given that only E/I ratio (deep breathing) and 30/15 ratio (lying-to-standing) were associated with vitamin D,” the authors wrote.

In addition, the authors 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.

In another study, to evaluate cardiac autonomic neuropathy and heart rate variability they looked at the vitamin D status in type 2 diabetes. A total of 163 patients were recruited. Cardiac autonomic neuropathy was assessed using five tests according to Ewing’s protocol. The time and frequency domains of the heart rate variability were also evaluated. Patients were separated into three groups: vitamin D sufficient [25(OH)D ⩾ 20 ng/mL], vitamin D insufficient [10 ⩽ 25(OH)D < 20] and vitamin D deficiency [25(OH)D < 10] groups.

Both standard deviation of normal-to-normal RR intervals and square root of the average of the sum of the squares of the differences between adjacent NN intervals in the supine position were significantly lower in vitamin D deficient group. Low frequency/high frequency ratio in the upright position was significantly higher in the vitamin D deficient group. 25(OH)D levels are positively correlated with standard deviation of normal-to-normal RR intervals in the supine position. In multivariate logistic analysis, patients with vitamin D levels of 10 < 25(OH)D < 20 ng/mL showed borderline significantly lower cardiac autonomic neuropathy risk than those with 25(OH)D levels <10 ng/mL (odds ratio = 0.45 (0.23–1.01), p = 0.051).

For this study, vitamin D deficiency was significantly correlated with heart rate variability parameters. However, there was only borderline significant association between vitamin D concentration and presence of cardiac autonomic neuropathy.

Another study published in the journal Endocrine Practice suggests that vitamin D insufficiency is associated with reduced cardiovascular autonomic function among patients with type 2 diabetes.

The researchers enrolled 50 patients with type 2 diabetes to evaluate the association between cardiovascular autonomic function and vitamin D status.  The researchers measured vitamin D levels and assessed the patients’ cardiovascular autonomic function by testing their heart rate variability, or the variation in the time intervals between heart beats.

They found that low vitamin D status was associated with decreased heart rate variability.  They also found that participants with vitamin D deficiency (n=26), with deficiency defined as levels below 30 ng/ml, were more insulin resistant and had a higher body mass index.

“The results of this study demonstrated that vitamin D insufficiency is associated with reduced parasympathetic nerve function, with the association being stronger in younger persons with type 2 diabetes than in older individuals,” the researchers concluded.

Practice Pearls:

  • Vitamin D deficiency was significantly correlated with heart rate variability parameters.
  • The association between vitamin D and CAN is mainly driven by abnormalities in the parasympathetic nervous system.
  • Vitamin D insufficiency is associated with reduced parasympathetic nerve function, with the association being stronger in younger persons with type 2 diabetes than in older individuals.

The study was published in the online journal Diabetes Medicine, Oct. 2016: Maser R, Lenhard J, Pohlig R. Vitamin D Insufficiency is Associated with Reduced Parasympathetic Nerve Fiber Function in Type 2 Diabetes. Endocrine Practice, 2014.

Endocr Pract. 2015 Feb;21(2):174-81. doi: 10.4158/EP14332.OR.