Nav: Home

Study suggests new strategy against vascular disease in diabetes

February 26, 2018

Recent findings suggest a novel approach for protecting people with diabetes from their higher risk of advanced blood vessel disease, which sets the stage for early heart attacks and strokes.

Cardiovascular problems from atherosclerosis - plaque-like lesions forming in artery walls - are the major cause of death in people with type 2 diabetes and metabolic syndrome.

People with metabolic syndrome exceed the normal range for several clinical measurements: blood pressure, blood sugar levels, harmful lipids, body mass index, and belly fat.

The researchers studied mice with metabolic syndrome. The mice were obese and had impaired glucose tolerance, a sign of pre-diabetes. In the study, an insulin-mimicking synthetic peptide called S597 was shown to both reduce blood sugar levels and slow the progression of atherosclerotic lesions.

Insulin, even when it controls diabetes, does not prevent atherosclerosis.

The findings are published in the Feb. 26 issue of Diabetes, a peer-reviewed scientific journal of the American Diabetes Association.

The senior author is Karin E. Bornfeldt, University of Washington School of Medicine professor of medicine, Division of Metabolism, Endocrinology and Nutrition. Jenny Kanter, UW research assistant professor of medicine, was the lead author. They are scientists at the UW Medicine Diabetes Institute.

The study was conducted as a research collaboration with Novo Nordisk A/S.

Although S597 is composed of a single chain of amino acids and looks nothing like insulin, S597 can still activate insulin receptors. But, unlike insulin, it's more selective in what it turns on inside the cells.

This study showed that, when S597 binds to insulin receptors, it preferentially activated a signaling arm known as the Akt arm, which is associated with lowering blood sugar levels and with other beneficial effects. It only weakly activated, or may have even prevented the activation of, another signaling arm, called the Erk arm, that is suspected of causing undesirable side effects.

The researchers were impressed by the mechanisms behind the S597 slow-down of atherosclerotic lesions.

Atherosclerosis starts with fatty streaks appearing in blood vessel walls. As the atherosclerotic lesion grows, inflammation provoked by obesity and recruitment of immune cells can speed the growth of the plaque.

Certain white blood cells, particularly monocytes that participate in inflammation, and macrophages, or "big eaters" that are supposedly the bloodstream's cleanup crew, are among the culprits. They can become overladen by engulfing lipids, and can turn into foam cells. These cells gather, and then perish. The core of the lesion fills with dead cells and other debris. If it ruptures, a clot can rapidly form in the vessels of the heart or brain.

In mice given S597, the problem with excessive white cells in the lesion seems to be nipped at its source: the early stages of production of inflammatory monocytes and macrophages. The S597 treated mice did not seem prone to the high white cell count characteristic of the inflammation induced by metabolic syndrome and obesity.

In fact, the amount of blood-forming stem cells in the bone marrow was lowered to levels observed in lean, healthy mice. These stem cells exhibited less activity from the undesirable signaling pathway originating in the insulin receptors.

The numbers of macrophages dying in the lesion were also fewer. While the number of intact cleanup cells rose, the relative content of macrophages in the lesion cores did not go up. The S597 may have either kept more macrophages alive longer or impeded their pile up.

Probably because of all this influence on white cells, the lesions did not grow with the rapidity expected in diabetes and metabolic syndrome. The researchers also saw that lesions with debris-filled cores were less common in these mice.

The researchers noted that the S597 did not alter cholesterol levels in the plasma or systemic inflammation overall.

"Cholesterol lowering drugs like statins are making a big impact in our ability to prevent cardiovascular disease associated with metabolic syndrome and diabetes," Bornfeldt said. "We think that the results of this new study provide a conceptually novel treatment strategy to explore as an additional possibility for protecting against advanced atherosclerosis associated with metabolic syndrome and type 2 diabetes."

There is only one previous study of the effects of S597 in living organisms. This new study is believed to be the first reported to evaluate the effects of S597 on the blood vessel system.
-end-
Funding for this work came in part from National Institutes of Health grants and from a STAR postdoctoral fellowship from Novo Nordisk.

Three researchers on the study are employed by Novo Nordisk A/S, which also supplied the S597 peptide for testing.

University of Washington Health Sciences/UW Medicine

Related Diabetes Articles:

Maternal gestational diabetes linked to diabetes in children
Children and youth of mothers who had gestational diabetes during pregnancy are at increased risk of diabetes themselves, according to new research published in CMAJ (Canadian Medical Association Journal).
Two diabetes medications don't slow progression of type 2 diabetes in youth
In youth with impaired glucose tolerance or recent-onset type 2 diabetes, neither initial treatment with long-acting insulin followed by the drug metformin, nor metformin alone preserved the body's ability to make insulin, according to results published online June 25 in Diabetes Care.
People with diabetes visit the dentist less frequently despite link between diabetes, oral health
Adults with diabetes are less likely to visit the dentist than people with prediabetes or without diabetes, finds a new study led by researchers at NYU Rory Meyers College of Nursing and East Carolina University's Brody School of Medicine.
Diabetes, but not diabetes drug, linked to poor pregnancy outcomes
New research indicates that pregnant women with pre-gestational diabetes who take metformin are at a higher risk for adverse pregnancy outcomes -- such as major birth defects and pregnancy loss -- than the general population, but their increased risk is not due to metformin but diabetes.
New oral diabetes drug shows promise in phase 3 trial for patients with type 1 diabetes
A University of Colorado Anschutz Medical Campus study finds sotagliflozin helps control glucose and reduces the need for insulin in patients with type 1 diabetes.
Can continuous glucose monitoring improve diabetes control in patients with type 1 diabetes who inject insulin
Two studies in the Jan. 24/31 issue of JAMA find that use of a sensor implanted under the skin that continuously monitors glucose levels resulted in improved levels in patients with type 1 diabetes who inject insulin multiple times a day, compared to conventional treatment.
Complications of type 2 diabetes affect quality of life, care can lead to diabetes burnout
T2D Lifestyle, a national survey by Health Union of more than 400 individuals experiencing type 2 diabetes (T2D), reveals that patients not only struggle with commonly understood complications, but also numerous lesser known ones that people do not associate with diabetes.
A better way to predict diabetes
An international team of researchers has discovered a simple, accurate new way to predict which women with gestational diabetes will develop type 2 diabetes after delivery.
The Lancet Diabetes & Endocrinology: Older Americans with diabetes living longer without disability, US study shows
Older Americans with diabetes born in the 1940s are living longer and with less disability performing day to day tasks than those born 10 years earlier, according to new research published in The Lancet Diabetes & Endocrinology journal.
Reverse your diabetes -- and you can stay diabetes-free long-term
A new study from Newcastle University, UK, has shown that people who reverse their diabetes and then keep their weight down remain free of diabetes.
More Diabetes News and Diabetes Current Events

Best Science Podcasts 2019

We have hand picked the best science podcasts for 2019. Sit back and enjoy new science podcasts updated daily from your favorite science news services and scientists.
Now Playing: TED Radio Hour

Rethinking Anger
Anger is universal and complex: it can be quiet, festering, justified, vengeful, and destructive. This hour, TED speakers explore the many sides of anger, why we need it, and who's allowed to feel it. Guests include psychologists Ryan Martin and Russell Kolts, writer Soraya Chemaly, former talk radio host Lisa Fritsch, and business professor Dan Moshavi.
Now Playing: Science for the People

#538 Nobels and Astrophysics
This week we start with this year's physics Nobel Prize awarded to Jim Peebles, Michel Mayor, and Didier Queloz and finish with a discussion of the Nobel Prizes as a way to award and highlight important science. Are they still relevant? When science breakthroughs are built on the backs of hundreds -- and sometimes thousands -- of people's hard work, how do you pick just three to highlight? Join host Rachelle Saunders and astrophysicist, author, and science communicator Ethan Siegel for their chat about astrophysics and Nobel Prizes.