Administering ursodeoxycholic acid (UDCA) can stave off the tendency of statins to induce glucose intolerance and diabetes, a study by a group of researchers in China has found.
Statins are prescribed to people with a high risk of cardiovascular disease. They work by blocking the activity of an enzyme involved in the metabolic pathway that produces LDL, or “bad”, cholesterol. Statins are on the World Health Organization’s list of essential medicines and among the most sold drugs worldwide.
However, many studies have found statins could increase the risk of developing diabetes. “It has been known for a few years now that statins can induce glucose intolerance and even frank diabetes in some people,” Dr. V. Mohan, chairman of the Madras Diabetes Research Foundation, Chennai, told The Hindu.
He added that doctors have continued to prescribe them because statins’ benefits “far outweigh the risk”. Nonetheless, the mechanism by which statins have this effect has been unclear.
In the study, published in February in the journal Cell Metabolism, the researchers reported one mechanism through which statins could increase glucose intolerance, involving UDCA, a bile acid.
The team recruited 30 people with atorvastatin and 10 without and tracked their metabolism for four months. They reported that the faeces of those taking atorvastatin had a reduced abundance of bacteria of the genus Clostridium and that these individuals had “altered serum and faecal bile acid profiles” as well.
The gut microbiome is a community of bacteria in the gut in a symbiotic relationship with the body. The researchers found that the Clostridium-deficient microbiome inhibited enzymes called hydroxysteroid dehydrogenases and lowered UDCA.
They also verified an idea that “the decreased Clostridium-rich microbiota might influence bile acid synthesis and excretion and impair glucose metabolism” in a 12-week study of mice.
To check the role of UDCA, they recruited five participants on statins and administered 10-13 mg/kg (of body weight) of UDCA per day. After two months, they found the individuals’ HbA1C levels, among others, were “substantially decreased”.
They concluded that “UDCA restored impaired glucose homeostasis without limiting the lipid-lowering effect of statin”.
Dr. Mohan called the finding “good news” and “a new angle” but also said the underlying hypothesis will have to be tested in randomised clinical trials.
