In a new study, "Loss-of-function mutations in SLC30A8 protect against type 2 diabetes," a rare gene mutation found in some people prevents them from developing type 2 diabetes, whether or not they're obese, according to a March 2, 2014 Fox News article, "Gene mutation may prevent Type 2 diabetes." The New York Times recently also reported on the new study's results published online March 2, 2014 in Nature Genetics.
What the new study explained focused on researching 150,000 people who had a genetic a mutation that destroys a gene used by pancreas cells – where insulin is made. People with the mutation were found to produce slightly higher levels of insulin and have slightly lower blood glucose levels for life.
As a result, that the mutation reduces diabetes risk by two-thirds – even among people who are overweight.
Loss-of-function mutations protective against human disease provide in vivo validation of therapeutic targets, but none have yet been described for type 2 diabetes (T2D) until this new study, explains the study's abstract. The idea is that some people have a mutation on certain genes that greatly reduces the risk of developing type 2 diabetes, but not totally. It's more like a two-thirds reduction risk.
The genetic mutation could lead to the development of a drug that destroys a gene
Now that the new finding which shows some people have the benefit of a mutation that destroys a gene could lead to the development of a drug for people with type 2 diabetes who obviously don't have the gene that prevents type 2 diabetes. The drug manufacturer, Pfizer, which helped finance the study, cautions that bringing a new drug to market can take 10 to 20 years. But the idea that a prescription drug might be developed in one or two decades is a surprise for big pharmaceutical corporations.
So if it doesn't matter whether the person is obese, if you have the genetic mutation, it works by reducing the risk of developing type 2 diabetes by two-thirds. The mutation destroys a gene used by pancreas cells where insulin is made. Those with the mutation seem to make slightly more insulin and have slightly lower blood glucose levels for their entire lives.
Drug companies are interested
Pfizer, which helped finance the study, and Amgen, which owns a company whose data played a key role in the research, are starting programs aimed at developing drugs that act like the mutation, the companies said.
“The study is a tour de force, and the authors are the top people in the field,” said Dr. Samuel Klein, director of the center for human nutrition at Washington University School of Medicine, who was not involved in the study.
This is the first time in diabetes research that a mutation that destroys a gene has proved beneficial, noted Louis Philipson, director of the Kovler Diabetes Center at the University of Chicago. For drug development, he said, “that is very powerful.”
The same mutation that protects people from diabetes destroys one copy of the gene, known as ZnT8, has the opposite effect in some strains of mice. Destroying that gene actually causes diabetes in the animals. But for humans, the mutation works.
So far, Dr. Stefanson said, none has been found. With his data he has established that people with the mutation are no more likely to get 750 diseases he searched for.
Scientists observe that epigenetic changes could explain type 2 diabetes, according another new study by different researchers
People with type 2 diabetes have epigenetic changes on their DNA that healthy individuals do not have. This has been shown in a major study by a different team of researchers at Lund University. The researchers also found epigenetic changes in a large number of genes that contribute to reduced insulin production. This new study is different from the study in Nature Genetics, "Loss-of-function mutations in SLC30A8 protect against type 2 diabetes,"
"This shows that the risk of developing type 2 diabetes is not only genetic, but also epigenetic", said Charlotte Ling, who led the Lund University study, "Genome-Wide DNA Methylation Analysis of Human Pancreatic Islets from Type 2 Diabetic and Non-Diabetic Donors Identifies Candidate Genes That Influence Insulin Secretion," published online March 6, 2014 in PLOS Genetics.
Epigenetic changes occur as a result of factors including environment and lifestyle, and can affect the function of genes
Charlotte Ling and her colleagues have analyzed insulin- producing cells of both healthy individuals and patients with type 2 diabetes. The analysis revealed epigenetic changes in approximately 800 genes in those with type 2 diabetes. Over 100 of the genes also had altered expression and many of these could contribute to reduced insulin production. Reduced insulin production is one of the underlying causes of type 2 diabetes.
In order to work out which is the chicken and which is the egg, i.e. whether the epigenetic changes are a consequence of the disease or if the disease is a result of the changes, the researchers also investigated whether healthy individuals had epigenetic changes caused by age, BMI and raised blood sugar levels.
"We were able to observe that a number of epigenetic changes had already taken place in healthy subjects as a result of age or high BMI, and were therefore able to conclude that these changes could contribute to the development of the disease", said Charlotte Ling, according to a March 7, 2014 news release, Epigenetic changes could explain type 2 diabetes. "Unlike genes that can't be changed, epigenetic changes are reversible", added Tasnim Dayeh, first author of the publication in PLOS Genetics.
Drugs that cause epigenetic changes have long been used in the treatment of cancer and epilepsy. The new survey changes the view of epigenetics in relation to diabetes, according to Charlotte Ling. "It shows that epigenetics is of major significance for type 2 diabetes, and can help us to understand why people develop the condition. This also opens the way for the development of future drugs."
What is epigenetics?
The cells of the body contain our genetic make-up (DNA), which contains genes. Our genes are inherited and cannot be altered. On the genes are epigenetic modifications, for example, 'methyl groups', which affect the expression and function of the genes, for example whether they are 'on' or 'off'. The methyl groups can be influenced in different ways through exercise, diet and lifestyle, in a process known as DNA methylation.
This is epigenetics, a relatively new research field that has received an increasing amount of interest in recent years. Also see, "Animal study suggests that newborn period may be crucial time to prevent later diabetes." Or check out, "Most people with diabetes do not meet treatment goals."