BETHESDA, MD—Increased intake of omega-3 fatty acids may partially reverse the autonomic dysfunction associated with type 2 diabetes, said James O’Keefe, MD, at the first International Workshop on Omega-3 Fatty Acids, Diabetes and Cardiovascular Risk.
Patients with diabetes typically show chronically elevated heart rates, and marked reduction in heart rate variability (HRV), both of which reflect autonomic dysregulation and correlate with increased risk of cardiovascular events.
“When I, as a cardiologist, see diabetes it is a red flag. I consider it the same as frank cardiovascular disease,” said Dr. O’Keefe, of the Mid-America Heart Institute, Kansas City. “I don’t think we are preventing CV events very well in our diabetic patients,” he said, noting the fivefold increase in sudden cardiac death in diabetics compared with normoglycemic individuals.
Researchers are beginning to elucidate the role of the autonomic nervous system in regulating cardiac function, and how these processes are disordered in the context of diabetes, which is characterized by an imbalance in sympathetic versus parasympathetic activity. Patients typically show chronically increased sympathetic drive, and a concomitant dysfunction of parasympathetic control.
Heart rate is under parasympathetic control, and resting heart rate is a remarkable predictor of CV event risk. A high resting heart rate of 80–100 bpm is reflective of increased sympathetic but decreased parasympathetic activity, and it is a very good marker for impending events. “It is like running the engine at 5,000 rpm when you don’t need to. This is very common in patients with type 2 diabetes,” said Dr. O’Keefe.
Delayed resting rate recovery is another typical finding. People with the best cardiovascular health, such as trained athletes, have resting rates of 40–50 bpm, and easily go up to 180–200 on treadmill tests. They recover to resting rates quickly, dropping 50–60 beats per minute in the first minute. People with cardiovascular disease, and many diabetics, cannot get their heart rates up that high, but they return from their peak to resting rates much more slowly.
High beat-to-beat variability, measured as the standard deviation of all R-R intervals on 24-hour Holter monitoring, correlates with a big difference in mortality. “Whether it is cause or marker we don’t know, but it is a clear indicator,” said Dr. O’Keefe.
“Insulin resistance heightens sensitivity to alpha stimulation, resulting in increased vasoconstriction. You get destruction of autonomic fibers in the heart as diabetes progresses, along with loss of normal parasympathetic function, reduced HRV, loss of nocturnal parasympathetic dominance, and loss of beta-stimulation-mediated vasodilation in the peripheral vasculature.”
The exact mechanisms by which insulin resistance predisposes to alpha stimulation and loss of parasympathetic function are still unknown. But Dr. O’Keefe suggested that, “it very well could be prostaglandin related—that is, an increase in omega-6 eicosanoids, resulting in increased prostaglandin synthesis.”
He and his colleagues have begun looking at omega-3 fatty acids, especially docosahexaenoic acid (DHA), and its effects on HRV and other parasympathetic mediated functions. “There’s some very promising preliminary data that omega-3’s, especially DHA, can increase HRV, decrease resting heart rate, and change QT dispersion,” he said.
Erik Berg Schmidt, MD, and colleagues at the Department of Medicine, Hjorring Hospital, Denmark, have also been studying the effects of omega-3’s on autonomic and cardiovascular function.
“We looked at 55 post-infarction patients with ejection fractions under 40% and very poor ventricular function, and compared omega-3 supplementation (5.2 g/day) with olive oil supplementation for 12 weeks. We saw a highly significant increase in HRV in those receiving the omega-3s,” said Dr. Schmidt, speaking at the workshop. He also noted a small, non-significant decrease in the number of ventricular extrasystoles in those receiving the omega-3’s (Christensen JH et al. Ugeskr Laeger 1997;159(37): 5525–9).
Working with investigators at Aalborg Hospital, Dr. Schmidt also looked at the effect of omega-3 intake from fish and seafood in a cohort of 52 post-infarction patients not receiving supplements. The omega-3 content in platelets was directly linked with weekly fish intake, and also correlated with increased HRV (Christiansen JH et al. Am J Cardiol 1997;79(12): 1670–3).
In a study not yet published, the Danish researchers measured DHA and EPA content in adipose tissue and granulocytes obtained from 291 subjects who underwent angiography for suspected coronary artery disease. Fatty acid content of adipose tissue did not correlate with HRV. But granulocyte fatty acid content was highly predictive. Those who had the highest DHA levels in the granulocytes also had the highest HRV. No such effect was observed with EPA.
“We had 30 type 2 diabetics in this cohort, and when we divided them into platelet DHA tertiles, those with the highest platelet DHA had the highest HRV,” said Dr. Schmidt. Interestingly, the relationship between omega-3’s and HRV appears to be much more robust in men than women. This gender disparity has been observed in healthy volunteers as well as diabetics and CVD patients. The reason for it is not yet clear.
THE REDUX: Diabetes is characterized by chronically increased sympathetic nervous system activity, and concurrent loss of parasympathetic control. This results in high resting heart rate, slow return from peak to resting rate, and low heart rate variability. All of these correlate with increased risk of cardiovascular events. There is evidence that omega-3 fatty acids, both from seafood and from supplements, can improve heart rate variability.
