Birmingham, AL—A common drug used to treat high blood pressure and angina is showing promise for improving T1D, according to a small study that builds on previous research.
Researchers advised that T1D patients taking verapamil continued to show benefits lasting at least 2 years. The report in Nature Communications pointed out that those patients required less daily insulin within 2 years after the disease was first diagnosed and demonstrated evidence of unexpected immunomodulatory benefits.
On the other hand, according to University of Alabama at Birmingham researchers, the benefits were tied to continued use of the medication. They noted that, in participants who discontinued the drug after a year, the disease at 2 years was similar to those who never used verapamil at all.
Liquid chromatography–tandem mass spectrometry of blood serum samples was used to examine changes in circulating proteins in patients on verapamil treatment. Researchers found that 53 proteins showed significant alterations in response to verapamil over time, and some of those are involved in immune modulation and autoimmunity of T1D.
For example, chromogranin A (or CHGA) was downregulated with treatment, according to the study. Researchers determined that serum CHGA levels in healthy, nondiabetic volunteers were about twofold lower than in T1D patients, whose levels dropped to similar levels after a year.
"Thus, serum CHGA seems to reflect changes in beta-cell function in response to verapamil treatment or Type 1 diabetes progression and therefore may provide a longitudinal marker of treatment success or disease worsening," Anath Shalev, MD, of the Comprehensive Diabetes Center at the University of Alabama at Birmingham, stated. "This would address a critical need, as the lack of a simple longitudinal marker has been a major challenge in the Type 1 diabetes field."
CHGA has been identified as an autoantigen in T1D that sparks immune T cells involved in the autoimmune disease. Researchers sought to determine if verapamil affected T cells, determining that several proinflammatory markers of T follicular helper cells, including CXCR5 and interleukin 21, were significantly elevated in monocytes in T1D patients compared with healthy controls.
"Now our results reveal for the first time that verapamil treatment may also affect the immune system and reverse these Type 1 diabetes-induced changes," stated lead researcher, Dr. Anath Shalev. "This suggests that verapamil, and/or the Type 1 diabetes improvements achieved by it, can modulate some circulating proinflammatory cytokines and T helper cell subsets, which in turn may contribute to the overall beneficial effects observed clinically."
Dr. Shalev and colleagues pointed out that their study had a small number of subjects, and the findings need to be confirmed by larger clinical studies, such as a current verapamil-type 1 diabetes study ongoing in Europe.
Still, the preservation of some beta-cell function is seen as promising. "In humans with type 1 diabetes, even a small amount of preserved endogenous insulin production—as opposed to higher exogenous insulin requirements—has been shown to be associated with improved outcomes and could help improve quality of life and lower the high costs associated with insulin use," Dr. Shalev stated. "The fact that these beneficial verapamil effects seemed to persist for two years, whereas discontinuation of verapamil led to disease progression, provides some additional support for its potential usefulness for long-term treatment."
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