With commentary by lead study author Yulia Khodneva, MD, PhD, a researcher and postdoctoral scholar at the University of Alabama at Birmingham.
The research is preliminary, she cautions. The researchers looked at only one point in time and it wasn't designed to look at verapamil as a blood sugar lowering medicine. They cannot prove cause and effect. Much more research is needed, including a randomized clinical trial, in which researchers would assign those with diabetes to take verapamil and compare them to those who do not take it, following all over time to see the effect on blood glucose levels. That study is now recruiting patients. "Our study is a first step," Dr. Khodneva says. The study is published in Diabetes Research and Clinical Practice.
For the current study, Dr. Khodneva and her colleagues evaluated nearly 5,000 men and women with diabetes. They were participants in a larger study designed to look at stroke. There was no information on which men and women had type 1 and which had type 2 diabetes. The majority were on diabetes medicines, insulin or oral agents or both.
Of the 5,000, 1,484 were on calcium channel blockers, including 174 on verapamil. Those taking verapamil had lower fasting blood glucose levels, about 10 mg/dL lower than the non users. The biggest difference was found between those on insulin taking verapamil, who averaged a blood glucose of 118 mg/dl, compared to non users of any calcium channel blockers, who had an average blood glucose of 156. (Fasting glucose of 126 is diagnosed as diabetes; under 100 is normal.) The difference was not statistically significant. However, the difference would translate to ''about a 1 percent change in AIC," which could be the difference between normal and not, Dr. Khodneva says.
When used for cardiovascular problems, a calcium channel blocker prevents calcium from entering the cells of the heart and blood vessel walls, in the process relaxing the blood vessels so the heart doesn't have to pump as hard. Researchers have more recently found that the medicine also reduces expression of a protein, TXNIP, that increases in the insulin-producing beta cells in the pancreas in response to diabetes. If the TXNIP rises too much, it can kill off the beta cells, experts have found.
The new study was triggered by basic research in the lab of Dr. Anath Shalev, director of the UAB Comprehensive Diabetes Center, finding that verapamil prevented the death of insulin-producing beta cells in animals by reducing the expression of the TXNIP. It also rescued animals from diabetes and improved obesity-linked diabetes.
The study findings are generating some ''questions that need to be answered for the long term," says Matthew Freeby, MD, director of the UCLA Diabetes Center of Santa Monica and associate director of the Diabetes Clinical Programs of the UCLA Health System. He reviewed the findings.
"We need to do a head-to-head study of using calcium channel blockers versus not, and see if it has an effect on patients," says Dr. Freeby, also an assistant professor of medicine at UCLA's David Geffen School of Medicine. Among the limitations of the current study, he says, are that they have just one glucose reading in a 24-hour period. That doesn't capture the peaks and valleys. An AIC measure, which reflects glucose levels over the past two to three months, would have been good information to have, he says.
A 1% drop in AIC, which was estimated to occur in those on the verapamil and insulin, is definitely a good drop, Dr. Freeby says. While the research is preliminary, he thinks it should continue. "There is good data on the non-human side in basic research to suggest that calcium channel blockers may have an effect on the insulin-producing cells in the pancreas, the beta cells, and it may be a positive effect."
Currently, UAB researchers are recruiting for a clinical trial comparing verapamil with placebo in 52 people, ages 18 to 45, recently diagnosed with type 1 diabetes. Half the participants will take daily verapamil for a year; half will take placebo for the same time. Neither group will know which they are taking.
The researchers will then determine if the verapamil helps beta cells survive and improves insulin production, compared to the placebo.