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Blood Sugar Control for Diabetes: Asking the Heart Questions

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Glucose testing

Credit: Thinkstock

When most people think about risk factors for cardiovascular disease, they likely think of blood pressure readings or cholesterol levels. But here’s something else that should be high on that list: diabetes. That’s because people with diabetes are roughly twice as likely to die of heart disease than other folks [1]. Yet the issue of how best to help such people lower their cardiovascular risks remains a matter of intense debate. Some studies have suggested that part of the answer may lie in tightly controlling blood sugar (glucose) levels with a strict regimen of medications and monitoring [2]. Other research has shown that the intense effort needed to keep blood glucose levels under tight control might not be worth it and may even make things worse for certain individuals [3].

Now, a follow up of a large, clinical trial involving nearly 1,800 U.S. military veterans with type 2 diabetes—the most common form of diabetes—provides further evidence that tight blood glucose control may indeed protect the cardiovascular system. Reporting in The New England Journal of Medicine [4], researchers found a significant reduction in a composite measure of heart attacks, strokes, heart failure, and circulation-related amputations among the vets who maintained tight glucose control for about five and a half years on average. What’s particularly encouraging is most of the cardiovascular-protective benefit appears to be achievable through relatively modest, rather than super strict, reductions in blood glucose levels.


Stem Cell Science: Taking Aim at Type 1 Diabetes

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human stem cell-derived beta cells

Caption: Insulin-producing pancreatic beta cells (green) derived from human embryonic stem cells that have formed islet-like clusters in a mouse. The red cells are producing another metabolic hormone, glucagon, that regulates blood glucose levels. Blue indicates cell nuclei.
Credit: Photo by B. D. Colen/Harvard Staff; Image courtesy of Doug Melton

For most of the estimated 1 to 3 million Americans living with type 1 diabetes, every day brings multiple fingerpricks to manage their blood glucose levels with replacement insulin [1,2]. The reason is that their own immune systems have somehow engaged in friendly fire on small, but vital, clusters of cells in the pancreas known as the islets—which harbor the so-called “beta cells” that make insulin. So, it’s no surprise that researchers seeking ways to help people with type 1 diabetes have spent decades trying a find a reliable way to replace these islets.

Islet replacement has proven to be an extremely difficult research challenge for a variety of reasons, but exciting opportunities are now on the horizon. Notably, a team of researchers, led by Douglas Melton of Harvard University, Cambridge, MA, and partially funded by NIH, reported groundbreaking success just last week in spurring a human embryonic stem cell (hESC) line and two human-induced pluripotent stem (iPS) cell lines to differentiate into the crucial, insulin-producing beta cells. Not only did cells generated from all three of these lines look like human pancreatic beta cells, they functioned like bona fide, glucose-responsive beta cells in a mouse model of type 1 diabetes [3].


Bionic Pancreas for Type 1 Diabetes

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Ed Damiano and son David

Caption: Boston University researcher Ed Damiano with his son David, who has type 1 diabetes, in 2002.
Credit: Toby Milgrome

From taking selfies to playing Candy Crush, smart phones are being put to a lot of entertaining uses. But today I’d like to share an exciting new use of mobile health (mHealth) technology that may help to save lives and reduce disability among people with type 1 diabetes—an advance inspired by one researcher’s desire to help his son.

By teaming a smart phone with a continuous glucose monitor and two pumps designed to deliver precise doses of hormones, a team from Boston has created a bionic pancreas that appears to control blood glucose levels in people with type 1 diabetes more effectively than current methods. That is a significant achievement because if blood glucose levels are either too high or too low, there can be serious health consequences.

In a healthy body, the pancreas masterfully regulates blood glucose levels by orchestrating the secretion of insulin and another hormone, called glucagon, which raises blood glucose. These hormones work together like an automatic thermostat, raising and lowering blood glucose when appropriate. However, in type 1 diabetes, the pancreas produces little or no insulin, leading to increased levels of glucose that gradually damage blood vessels, kidneys, and nerves, raising the risk of blindness and amputations.


DNA Analysis Finds New Target for Diabetes Drugs

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ATCG's with a silhouette of people

Credit: Jane Ades, National Human Genome Research Institute, NIH

Type 2 diabetes (T2D) tends to run in families, and over the last five years the application of genomic technologies has led to discovery of more than 60 specific DNA variants that contribute to risk. My own research laboratory at NIH has played a significant role in this adventure. But this approach doesn’t just provide predictions of risk; it may also provide a path to developing new ways of treating and preventing this serious, chronic disease that affects about 26 million Americans.

In an unprecedented effort aimed at finding and validating new therapeutic targets for T2D, an international team led by NIH-funded researchers recently analyzed the DNA of about 150,000 people across five different ancestry groups. Their work uncovered a set of 12 rare mutations in the SLC30A8 gene that appear to provide powerful protection against T2D, reducing risk about 65%—even in the face of obesity and other risk factors for the disease [1].


More Beta Cells, More Insulin, Less Diabetes

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Artist redition of a liver, WAT fat, and BAT fat cells combining with green dots representing betatrophin combining to induce pancreatic cells

Caption: Betatrophin, a natural hormone produced in liver and fat cells, triggers the insulin-producing beta cells in the pancreas to replicate
Credit: Douglas Melton and Peng Yi

Type 2 diabetes (T2D) has arguably reached epidemic levels in this country; between 22 and 24 million people suffer from the disease. But now there’s an exciting new development: scientists at the Harvard Stem Cell Institute have discovered a hormone that might slow or stop the progression of diabetes [1].

T2D is the most common type of diabetes, accounting for about 95% of cases. The hallmark is high blood sugar. It is linked to obesity, which increases the body’s demand for more and more insulin. T2D develops when specific insulin-producing cells in the pancreas, called beta cells, become exhausted and can’t keep up with the increased demand. With insufficient insulin, blood glucose levels rise. Over time, these high levels of glucose can lead to heart disease, stroke, blindness, kidney disease, nerve damage, and even amputations. T2D can be helped by weight loss and exercise, but often oral medication or insulin shots are ultimately needed.


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