This blood pressure pill could end injections for diabetics

By Mark Waghorn via SWNS

A pill that has treated high blood pressure for over 40 years could end painful injections for diabetics, according to new research.

The medication, called verapamil, boosts beta cells in the pancreas that produce insulin.

They are lost in type 1 diabetes patients, who need regular shots of the glucose controlling hormone. There is no current oral therapy.

The auto-immune disease is caused by an over-reaction of T-cells and cytokines that mistake the cells for foreign bodies.

Lead author Professor Anath Shalev, of the University of Alabama at Birmingham, said: "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.

"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."

Verapamil delayed disease progression, lowered insulin requirements and preserved some beta cell function.

The study in Nature Communications found patients required less daily insulin two years after first diagnosis of the disease.

They also showed evidence of surprising immuno-modulatory benefits. Continued medication was necessary.

Subjects who stopped daily doses after a year saw their disease worsen 12 months later.

Rates of deterioration were similar to those of a control group of diabetics who did not use verapamil at all.

The suggestion verapamil might serve as a potential type 1 diabetes drug was a serendipitous discovery by Prof Shalev.

The finding stemmed from more than two decades of basic research into a gene in pancreatic cells called TXNIP.

In 2014, her lab reported verapamil completely reversed diabetes in mice - paving the way for a clinical trial.

The Food and Drug Administration (FDA) in the US approved verapamil for the treatment of high blood pressure in 1981.

Four years ago Prof Shalev and colleagues reported the benefits of verapamil in a one-year clinical study.

They found regular oral administration of verapamil enabled patients with type 1 diabetes to produce higher levels of their own insulin.

It reduced their need for injected insulin to regulate blood sugar levels. The current study provides crucial mechanistic and clinical insights.

The US team scanned blood serum samples from subjects diagnosed with type 1 diabetes within three months of diagnosis and at one year of follow-up.

Fifty-three proteins showed significantly altered relative abundance over time in response to verapamil.

These included proteins known to be involved in immune modulation and autoimmunity of Type 1 diabetes.

The top serum protein altered by verapamil treatment was CHGA (chromogranin A) which was downregulated with treatment.

It is localized in secretory granules, including those of pancreatic beta cells, suggesting changed levels might reflect alterations in beta cell integrity.

In contrast, the elevated levels of CHGA at type 1 diabetes onset did not change in controls who did not take verapamil.

CHGA levels were also easily measured directly in serum using a simple test after a blood draw.

Lower levels in verapamil-treated volunteers correlated with better insulin production in a standard test of disease progression.

Also, serum CHGA levels in healthy, non-diabetic individuals were about twofold lower compared to those with type 1 diabetes.

After a year of verapamil treatment, patients had similar CHGA levels as healthy peers.

In the second year, CHGA levels continued to drop in verapamil-treated subjects.

But they rose in Type 1 diabetes subjects who discontinued verapamil during year two.

Prof Shalev explained: "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.

"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."

A genetic analysis showed verapamil promotes an anti-oxidative profile in human pancreatic cells.

Such protective changes might further explain the sustained improvements in pancreatic beta-cell function observed with continuous verapamil use.

Prof Shalev said the small study needs to be confirmed by a larger ongoing study in Europe. But the preservation of beta cells is promising.

She said: "In humans with Type 1 diabetes, even a small amount of preserved insulin production 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.

"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."

About 400,000 people are currently living with type 1 diabetes in the UK, including around 29,000 children.