A new study based on genetic testing of 150,000 people has found a rare mutation that protects even fat people from getting Type 2 diabetes. The effect is so pronounced — the mutation reduces risk by two-thirds — that it provides a promising new target for developing a drug to mimic the mutation’s effect.
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.
Already 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.
But Timothy Rolph, a Pfizer vice president, cautioned it can take 10 to 20 years to get a drug to market after discovering something new about human genetics and disease.
The study, published Sunday in Nature Genetics, involved a mutation so rare that finding it was only recently possible, with vast data from large numbers of people, researchers 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.”
For scientists, the result was a surprise because the same mutation that protects people from diabetes, by destroying 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.
The work began four years ago when a group of geneticists from academic institutions and Pfizer decided to search for gene mutations that protect against diabetes. Usually researchers look for mutations that increase — rather than decrease — the risk of diseases, with the aim of determining who gets a disease, and why.
The group started with populations in Finland and Sweden, where 28,000 people had been studied for years. The data included their ages, weights and diseases, including diabetes.
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