Mysterious link between high blood pressure and diabetes finally solved

BRISTOL, United Kingdom — Doctors have noted for decades that many hypertension (high blood pressure) patients also have diabetes — an inability to control their blood sugar. Up until now, the connection between the two conditions remained a mystery. Researchers from the University of Bristol and the University of Auckland, however, may finally have the answer.

Scientists have discovered that a small protein cell called glucagon-like peptide-1 (GLP-1) appears to “couple” the human body’s control over both blood sugar and blood pressure.

“We’ve known for a long time that hypertension and diabetes are inextricably linked and have finally discovered the reason, which will now inform new treatment strategies,” says senior study author Professor Julian Paton, Director of Manaaki Mãnawa – The Centre for Heart Research at the University of Auckland, in a media release.

The link connects to a sensory organ in the neck

Released by the wall of the gut after eating, GLP-1 works to stimulate insulin from the pancreas, which helps control blood sugar. Scientists have known about GLP-1’s function for some time, but they didn’t know about GLP-1’s additional ability to stimulate a small sensory organ in the neck called the carotid body.

The team used an unbiased and extensive genomics technique called RNA sequencing to read expressed gene messages within the carotid body among rats both with and without high blood pressure. Those experiments led to the discovery of a receptor that senses GLP-1 located within the carotid body. Importantly, this receptor wasn’t as adept among hypertensive rats.

“Locating the link required genetic profiling and multiple steps of validation.  We never expected to see GLP-1 come up on the radar, so this is very exciting and opens many new opportunities,” says senior study author David Murphy, Professor of Experimental Medicine from Bristol Medical School: Translational Health Sciences (THS).

“The carotid body is the convergent point where GLP-1 acts to control both blood sugar and blood pressure simultaneously; this is coordinated by the nervous system which is instructed by the carotid body,” Prof. Paton adds.

Could a new medication treat both conditions?

Both diabetes and hypertension can put an individual at increased risk of a cardiac event or heart disease. Even while on medication, many patients remain high-risk. Why? Most meds simply treat the symptoms, not the root cause.

“We’ve known that blood pressure is notoriously difficult to control in patients with high blood sugar, so these findings are really important because by giving GLP-1 we might be able to reduce both sugar and pressure together, and these two factors are major contributors to cardiovascular risk,” explains Prof. Rod Jackson, world-renowned epidemiologist from the University of Auckland.

“The prevalence of diabetes and hypertension is increasing throughout the world, and there is an urgent need to address this. Drugs targeting the GLP-1 receptor are already approved for use in humans and widely used to treat diabetes. Besides helping to lower blood sugar these drugs also reduce blood pressure, however, the mechanism of this effect wasn’t well understood,” comments lead study author Mr. Audrys Pauža, a British Heart Foundation-funded PhD student in Professor David Murphy’s lab in the Bristol Medical School.

“This research revealed that these drugs may actually work on the carotid bodies to enact their anti-hypertensive effect. Leading from this work, we are already planning translational studies in humans to bring this discover into practice so that patients most at risk can receive the best treatment available.”

Importantly, GLP-1 may be just the tip of the scientific iceberg. Researchers report several additional novel targets for potential studies moving forward.

The study is published in the journal Circulation Research.