International “Big Data” Study Offers Fresh Insights into T2D

World map

Caption: This international “Big Data” study involved hundreds of researchers in 22 countries (red).

It’s estimated that about 10 percent of the world’s population either has type 2 diabetes (T2D) or will develop the disease during their lives [1]. Type 2 diabetes (formerly called “adult-onset”) happens when the body doesn’t produce or use insulin properly, causing glucose levels to rise. While diet and exercise are critical contributory factors to this potentially devastating disease, genetic factors are also important. In fact, over the last decade alone, studies have turned up more than 80 genetic regions that contribute to T2D risk, with much more still to be discovered.

Now, a major international effort, which includes work from my own NIH intramural research laboratory, has published new data that accelerate understanding of how a person’s genetic background contributes to T2D risk. The new study, reported in Nature and unprecedented in its investigative scale and scope, pulled together the largest-ever inventory of DNA sequence changes involved in T2D, and compared their distribution in people from around the world [2]. This “Big Data” strategy has already yielded important new insights into the biology underlying the disease, some of which may yield novel approaches to diabetes treatment and prevention.

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Precision Medicine: Using Genomic Data to Predict Drug Side Effects and Benefits

Gene Variant and Corornary Heart DiseasePeople with type 2 diabetes are at increased risk for heart attacks, stroke, and other forms of cardiovascular disease, and at an earlier age than other people. Several years ago, the Food and Drug Administration (FDA) recommended that drug developers take special care to show that potential drugs to treat diabetes don’t adversely affect the cardiovascular system [1]. The challenge in implementing that laudable exhortation is that a drug’s long-term health risks may not become clear until thousands or even tens of thousands of people have received it over the course of many years, sometimes even decades.

Now, a large international study, partly funded by NIH, offers some good news: proof-of-principle that “Big Data” tools can help to identify a drug’s potential side effects much earlier in the drug development process [2]. The study, which analyzed vast troves of genomic and clinical data collected over many years from more than 50,000 people with and without diabetes, indicates that anti-diabetes therapies that lower glucose by targeting the product of a specific gene, called GLP1R, are unlikely to boost the risk of cardiovascular disease. In fact, the evidence suggests that such drugs might even offer some protection against heart disease.

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DNA Analysis Finds New Target for Diabetes Drugs

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].

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More Beta Cells, More Insulin, Less Diabetes

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. Continue reading