Scientists have found two surprising causes of diabetes — a pair of genes that didn’t seem to have anything to do with the disease.
Defects in either gene cause an unusual variant of the most common kind of diabetes.
Nobody knows why. But by showing that the genes can sabotage the body’s efforts to rein in high blood sugar levels, the new work “opens up a whole new pathway that has to be explored” to understand diabetes, said researcher Graeme Bell. And that might lead to new treatments.
The vast majority of diabetes is type 2 disease, which affects about 15 million Americans. It usually develops in people older than 40, especially if they’re overweight.
In contrast, the variant caused by the genes usually appears before age 25, often in adolescence or childhood. Together, the genes may account for 2 percent to 5 percent of type 2 cases, Bell said.
Bell is a professor of biochemistry, molecular biology and medicine at the Howard Hughes Medical Institute at the University of Chicago. He and an international team of researchers presented their findings in Thursday’s issue of the journal Nature.
In diabetes, blood sugar levels rise out of control because the body doesn’t secrete enough insulin, doesn’t respond normally to insulin, or has both problems. Diabetes can lead to such problems as kidney disease, blindness and nerve damage. The nerve damage and impaired circulation in the feet and legs can set the stage for amputation.
The variant caused by the genes is called maturity-onset diabetes of the young, or MODY. Another MODY gene had been found before, and Bell said at least one more remains to be uncovered.
The two genes in his study were already known to scientists, mostly for turning on other genes in the liver. The genes are also active in the intestine, kidney and the pancreas, which makes insulin, but it’s not clear what they do in those organs.
People with MODY don’t secrete enough insulin to handle high blood sugar levels, and it’s not clear yet why defects in the two genes would lead to that problem, Bell said.
The work suggests that as scientists hunt for genes that make people vulnerable to type 2 diabetes, they should consider those that regulate other genes, he said.
In an accompanying commentary, John Todd of Oxford University said the findings add “an exciting new dimension” to knowledge about the biology of diabetes and to the hunt for genes linked to common diabetes.