SITNFlash

Greetings SITN members!

This month’s newsletter discusses an important health topic: diabetes. Twenty million Americans are reported to have diabetes, but the actual number of affected individuals is even higher because many people are diabetic but remain undiagnosed. Although diabetes has been studied for decades, the underlying causes of this increasingly common disease are still under investigation. As this month’s newsletter describes, genetic technologies are bringing some answers, but also a lot more questions.

If you want to learn more about the biology behind diabetes, please join us for our free public seminar series, starting on September 21st! We're excited to be presenting a variety of topics, including a whole lecture entitled “Obesity and Diabetes” scheduled for Thursday October 12th at Harvard Medical School and Monday October 16th at the Mildred Ave. Community Center in Mattapan. Please see below for the full 2006 seminar series schedule, or visit our website at http://sitn.hms.harvard.edu/.

Enjoy!

--The SITN Staff

When we eat, a hormone called insulin controls how our bodies use the sugar in food to create energy. If a person’s body does not make or use insulin properly, a disease called diabetes results. Approximately 20 million Americans have diabetes, making it one of the major public health challenges of the new millennium. The vast majority of diabetic patients have what is called Type II diabetes, or adult-onset diabetes, because it occurs later in life. By working hard to maintain sugar levels in the blood, diabetic patients can continue to enjoy very healthy lives. However, serious complications can occur, including heart disease and blindness, so it is particularly important that we understand what causes diabetes and work to develop new treatments for this disease.

What causes diabetes?

Although there are likely to be numerous contributing factors, the greatest risk factors that have been identified for diabetes are age and obesity. In fact, the skyrocketing rate of diabetes in recent years can be traced to the obesity epidemic in America. Diabetes is also known to have a genetic component: if your parents or siblings have diabetes, you are at greater risk of developing the disease as well. Although scientists have worked hard to identify genes that can increase the risk of contracting diabetes, so far very few have been identified. Furthermore, none of these genes seem to play a major role in the disease, leaving the genetic component of diabetes poorly understood.

A new genetic risk factor?

In January of this year, researchers from the biopharmaceutical company deCode Genetics in Iceland identified a new human genetic risk factor for diabetes, an alternative form, or “allele” (pronounced: “ah-lee-al”), of a gene named TCF7L2. Every human has two copies of genes, one inherited from each parent. If both copies of TCF7L2 are of this newly discovered harmful allele, it increases one’s risk of diabetes by 141%. This gives TCF7L2 the distinction of being the gene with the largest role in the development of diabetes—at least that has been identified so far. The TCF7L2 gene makes a type of protein called a transcription factor that directs the cell to make other proteins. One of the proteins that TCF7L2 controls is in fact already known to control insulin activity. This connection with insulin, and therefore diabetes, suggests one way that this gene may affect the disease. Pharmaceutical companies are now actively working to develop drugs that can change TCF7L2 function, and ultimately the development of diabetes.

Scientific progress depends on the reproducibility of results by independent researchers, and the confirmation of the deCode study was published last month in the New England Journal of Medicine (NEJM). Although the link between diabetes and the harmful allele of TCF7L2 was not as strong as that reported in the deCode study, the researchers did confirm that the TCF7L2 variation is a serious risk factor for diabetes.

Genes = Destiny?

The unique design of the New England Journal of Medicine study allowed the researchers to go further with their analysis. This study was originally published in 2001, and was designed to look at the efficacy of diet and exercise in preventing diabetes. The researchers found that a low calorie diet and moderate exercise can reduce the risk of developing diabetes by 60% in overweight individuals. Remarkably, when researchers re-analyzed this data after the deCode study, they found that the overweight patients that did not start dieting or exercising were 80% more likely to develop diabetes if they had the harmful allele of TCF7L2. In contrast, the patients that had undertaken the lifestyle changes had a reduced risk of diabetes whether they possessed the harmful allele or not.

These results suggest that by controlling their weight and becoming more active, patients were able to counteract the increased risk caused by the harmful allele of TCF7L2. This is a great example of how our environment and lifestyle choices can interact with our genes to make us who we are. How diet and exercise affect the function of TCF7L2 is currently unknown and will undoubtedly be an active and exciting avenue of research.

-- Dodzie Sogah, Harvard Medical School

Primary Articles

1. Florez JC et al. TCF7L2 polymorphisms and progression to diabetes in the Diabetes Prevention Program. New England Journal of Medicine. July 20, 2006:p241-50
2. Grant SF et al. Variant of transcription factor 7-like 2 (TCF7L2) gene confers risk of type 2 diabetes. Nature Genetics. March 2006: p320-323

For More Information:

American Diabetes Association: <www.diabetes.org >

Here's the schedule for the 2006 lecture series! The series kicks off on September 21st with an introductory lecture entitiled "Making Sense of Science in the News," with a new lecture every week thereafter on a wide range of topics in the headlines, from mental health to global warming. Lastly, this year we will be continuing to offer or lectures on two night at two locations, so feel free to attend the seminar that is more convenient for you! Here is the full schedule:

Of course, this information may change as we get closer to the start of the series, so check http://sitn.hms.harvard.edu/ for the latest updates!