A rare genetic mutation may help explain why some families are more susceptible to diabetes and kidney failure, according to a new study led by University of Utah health scientists. They say the discovery, made within several generations of the same family, could eventually lead to better treatments for these conditions among a range of patients, whether they have inherited the mutation or not.

In the past, we have seen sporadic cases here and there, but this is the first family to demonstrate that this mutation may be inherited. Marcus Pezolesi, PhD, MPH, corresponding author of the study and U of U Health associate professor of internal medicine in the department of nephrology, says. What is exciting is that treatments are being developed that can improve this condition not only within this family but in the vast spectrum of patients with diabetes at risk of kidney disease.

The study, conducted in collaboration with the Joslin Diabetes Center and Harvard Medical School in Boston, appears in NPJ Genomic Medicine,

Scientists have long known that people who are overweight or obese produce less adiponectin, a hormone that promotes insulin sensitivity, inhibits cell death, and reduces inflammation. As a result, these individuals have a higher risk of developing insulin resistance, type 2 diabetes, kidney disease, and other life-threatening conditions.

To determine whether there may be a genetic cause for diabetic kidney disease, Pezolsi and his colleagues analyzed DNA samples from 14 members of a family collected at the Joslin Diabetes Center. In all, six family members over three generations had diabetes and end-stage kidney disease.

Digging deeper, the researchers used whole-genome sequencing to isolate a defect in a gene called ADIPOQ, which encodes the adiponectin protein. The mutation shortens the gene, disrupting its ability to produce the hormone, which breaks down ceramides, a fatty substance similar to cholesterol. As a result, people with the mutation have higher levels of ceramides. Previous studies suggest that ceramides are a driving force behind the onset of type 2 diabetes and may contribute to diabetic kidney disease.

In laboratory studies of human embryonic kidney cells, researchers found that just one copy of this mutation was able to reduce adiponectin production. Researchers determined that this mutation occurs in about one out of every 57,000 people.

Overall, carriers of the genetic mutation had approximately 85% less adiponectin and 30% higher levels of ceramides circulating in their blood relative to non-carriers within the same family, who were used as a control group.

Whats most exciting to me is that this discovery allows us to confirm decades of research in animals, says William Holland, PhD, study co-corresponding author and U Health Associate Professor of Nutrition and Integrative Medicine. physiology. The biological effects of adiponectin in regulating insulin sensitivity, glucose tolerance and ceramide levels are well established in rats, and the present study demonstrates that loss of adiponectin impairs metabolic health in humans.

Although the study was conducted in the same family, Holland says, its findings could have broad implications for the diagnosis and treatment of these conditions in many people. We can use these findings as a starting point for the development of personalized drugs that mimic the beneficial effects of adiponectin and reduce the risk of diabetes and kidney disease, he says.

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Detection Of Rare Genetic Mutation In A Family Could Lead To Better Diabetes Treatment - Nation World News