What is the role of uric acid as it relates to diabetes and pre-diabetes metabolic syndrome?
As a foot and ankle specialist I will regularly see the effects of high uric acid levels in the feet presenting as acute gout causing a very painful inflammation. Over time, gout can even cause a buildup of uric acid at a joint that literally causes the acid to begin to seep through the skin. Not only can an increased uric acid level affect the joints, but studies also suggest that it is a risk factor for cardiovascular disease, and recently there is growing evidence that an elevated uric acid level may have a role in the development of metabolic syndrome and diabetes. Research has shown that decreasing uric acid levels may help to prevent or reverse features of metabolic syndrome.
Uric acid is formed as the end product of purine metabolism. Purines are prevalent in meats, especially organ-meats such as liver and kidney so the common dietary advice is to limit these foods, but it appears to be more complex than that. For example, studies have also shown an association between high fructose corn syrup and elevated uric acid levels, and dysfunctional carbohydrate metabolism is also likely part of the metabolic equation that elevates uric acid levels and sets someone up for an acute gout attack.
Recent studies show that an increased uric acid level appears to be at least partly connected to hardening of the arteries through increased inflammation caused by the abnormally high uric acid level in the blood. This suggests that uric acid may play a causal role in the development of atherosclerosis and metabolic syndrome partially by instigating inflammation. Some researchers have shown that reducing uric acid by treatment with allopurinol significantly improves the health of the cells lining the blood vessels, the ability of some blood vessels to dilate, and the blood flow in general. Treating an elevated uric acid has been proposed as a new potential therapeutic approach for cardiovascular health.
A study has recently been published that looked at serum uric acid levels and their association with metabolic syndrome and carotid atherosclerosis in patients with type 2 diabetes. The researchers wanted to investigate whether elevated uric acid levels in the blood are associated with a higher risk of carotid atherosclerosis (“hardening of the arteries”) in people with type 2 diabetes and any associated risk for metabolic syndrome.
They looked at 395 men and 631 women 41-92 years of age. They used ultrasound imaging to measure the thickness of the carotid artery and the plaque that was present.
They found that those people who had higher uric acid levels were more likely to have been diabetic for a shorter period of time, have lower fasting blood glucose, lower glycohemoglobin, lower HDL-cholesterol and those people who had high uric acid levels were more likely to have associated higher BMI, higher C-reactive protein, higher triglycerides, higher waist circumference, higher systolic blood pressure, and insulin resistance.
They concluded that an elevated serum uric acid level is associated with metabolic syndrome and is an independent risk factor for carotid atherosclerosis in patients with type 2 diabetes.
This study was carried out in Shanghai, China. Metabolic syndrome is increasing in China because of the Westernization of diet and lifestyle. In other words they are eating more bad fats with a high calorie diet and participating in less physical activity. This apparently is more true of women than men. The current prevalence of metabolic syndrome among Chinese 35-64 years of age is 9.8% in men and 17.8% in women. Why is this? Activity levels? Some cultural factor?
The study did show that those people with a lower uric acid level had diabetes for a longer period of time, worse HbA1c and worse fasting plasma glucose. This was attributed to the increased passing of uric acid in the urine in the presence of high blood sugar levels from long-standing poorly controlled diabetes. In these cases more sugar is passed in the urine and the uric acid is going along as well.
So, somewhat oddly, increased uric acid can contribute to the development of metabolic syndrome of which prediabetes is a component, and diabetics with an increased uric acid have a higher risk for carotid atherosclerosis, but in advanced diabetes, the future risk of elevated uric acid and gout is apparently reduced through the increased passing of uric acid upon urination. Human metabolism is a puzzle with many pieces and many variables.