Approximately 8.2 million Americans and 60,000 North Carolinians suffer from Type 2 diabetes, a metabolic disorder involving insulin irregularities and high blood glucose levels. Scientists are now one step closer to solving the mystery of this disease with the recent discovery of a gene that could be responsible for up to 20 percent of Type 2 cases.
PTPN1, which was identified by a team of researchers at Wake Forest University’s School of Medicine, is one of many genes suspected of playing a role in the development of Type 2 diabetes. Its function is to encode the production of proteins that are needed for insulin signaling pathways to metabolize glucose. It is considered a novel gene because it is the first strong evidence for a gene that controls this insulin resistance, the most pronounced problem in Type 2 diabetes.
There are two forms of this gene—the first is found in 35 percent of the population and increases the risk of diabetes by 30 percent, while the second gene has a neutral or protective role in the body.
Identification of this gene in an individual will enable doctors to predict who is at risk for Type 2 and encourage patients to take preventative steps such as exercise, a healthy diet and medication.
The implications of such research do not end here. With an increased emphasis on personalized medicine, the discovery of this gene, along with continued research on diabetes, will allow researchers to target specific pathways in drug development and will help researchers think about methods to identify other related genes.
“Diabetes is a multifactorial disease—there isn’t one root cause that is common to all inflicted,” said Debbie Muoio, assistant professor in medicine at the Sarah Stedman Nutrition and Metabolism Center at Duke University. “Now we’re even closer to being able to treat each patient differently depending on the particular cause of the individual’s diabetes.”
Three different studies were conducted that investigated the genetic blueprints of groups susceptible to Type 2 diabetes. Two involved Caucasian subjects from North Carolina and the third consisted of Latino subjects from Texas and Colorado. The results showed that there is a strong correlation between the Latino population and the onset of diabetes in general, as well as the presence of PTPN1, said Donald Bowden, a biochemistry and internal medicine professor at Wake Forest and an author of the study, which was published in the November issue of the journal Diabetes.
This discovery comes at a time when doctors are seeing an explosion of Type 2 diabetes, even in children who used to only develop Type 1. Formerly known as juvenile diabetes, Type 1 is characterized by the body’s destruction of the cells needed to make insulin. Doctors attribute the increased frequency of diabetes to the obesity epidemic.
“If you have a genetic predisposition or a strong family history of diabetes and you feed the person wrong things, you’re going to get diabetes,” said Mark Feinglos, professor of medicine and chief of the endocrinology division at the Duke University Medical Center. “Obesity causes Type 2 diabetes—it’s like a one-two punch.”
To help treat these metabolic disorders, Duke leads the way, with more physicians than anywhere in the state to treat diabetes, Feinglos said. Many of these doctors are also involved with the many research investigations being conducted within the University.
The Sarah Stedman Nutrition and Metabolism Center has been involved in surveying different weight loss methods on both psychological and biochemical levels, as well as working with animal models to elucidate the mechanisms involved in this disease.
One of their most prominent current projects is metabolomics. Scientists are performing metabolic profiles that are indicative of an individual’s susceptibility to the disease, leading to clues toward developing therapeutic strategies.
In terms of Type 1 diabetes research, Duke scientists are working on building cells that can be used in the transplantation of dysfunctional pancreatic cells. Potential new technology would replace the traditional method of insulin injections, “an imperfect therapy,” said Chris Newgard, director of the Stedman Center. To do this, scientists have been using cells from organ donors, but because of a shortage they have turned to engineering stem cells and building a renewable source of cells for regulation of insulin and its survival in hostile Type 1 environments.
“Obesity is the root cause, and if we can’t stop obesity, we’re going to be looking at a really expensive and draining epidemic of diabetes,” Newgard said. “Clinical translation for weight loss is critical.”
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