A new study performed by researchers at the University of Utah Health suggests that a rare genetic mutation may help explain why some families are more likely to have diabetes and kidney failure.
They believe the finding, made within multiple generations of a single family, could lead to better treatments for these disorders in a wide range of patients, regardless of whether they inherited the mutation or not.
“In the past, we’ve seen,” according to Marcus Pezzolesi – the study’s corresponding author, “sporadic cases here and there, but this is the first family to demonstrate that this mutation can be inherited.”
“What’s exciting is,” as highlighted by the author, “that there are therapies being developed that could improve this condition not just within this family but more broadly among a vast spectrum of patients with diabetes who are at risk of kidney disease.”
The study, which was carried out in association with the Harvard Medical School and the Joslin Diabetes Center in Boston, is published in NPJ Genomic Medicine.
Adiponectin is a hormone that improves insulin sensitivity, prevents cell death, and reduces inflammation. Scientists have known for a long time that people who are overweight or obese make less adiponectin.
These people are therefore more vulnerable to insulin resistance, type 2 diabetes, renal disease, and other potentially fatal illnesses.
Pezzolesi and colleagues examined DNA samples taken from 14 members of a single family at the Joslin Diabetes Center to see if there might be a hereditary basis for diabetic kidney damage. Six members of the family, spanning three generations, all had end-stage kidney disease and diabetes.
To delve even further, the scientists employed whole genome sequencing to pinpoint a problem in the ADIPOQ gene, which produces the adiponectin protein. The mutation shortens the gene, preventing it from producing the hormone that breaks down ceramides, a fatty molecule comparable to cholesterol. People who carry the mutation consequently have greater ceramide levels. Ceramides may play a role in the development of type 2 diabetes and diabetic kidney disease, according to earlier investigations.
Single copies of this mutation were found to be sufficient to reduce adiponectin synthesis in laboratory tests of human embryonic kidney cells. According to the study’s findings, this mutation affects roughly one in every 57,000 individuals.
Overall, people who carried the genetic mutation had about 85% less adiponectin and 30% more ceramides in their blood than people in the same family who did not carry the mutation, who were used as a control group.
The study’s co-corresponding author and associate professor of nutrition and integrative physiology at the University of Utah Health, William Holland, Ph.D., adds, “What’s most exciting for me is that this finding allows us to confirm decades of research in animals.” The current study demonstrates that adiponectin deficiency negatively impacts metabolic health in people. This is consistent with the physiologic effects of adiponectin in modulating insulin sensitivity, glucose tolerance, and ceramide levels in mice.
Although the study was limited to a single family, Holland claims that its results could have a significant impact on how these illnesses are identified and treated in a wide range of patients.
According to him, “We can use these findings as a starting point for the development of personalized medicines that mimic the beneficial effects of adiponectin and diminishes the risk of diabetes and kidney disease.”
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