Published January 14, 2015
Over-the-counter allergy and asthma drugs helped obese, diabetic mice lose weight and control their blood sugar, researchers reported on Monday.
Three other studies strongly linked obesity and type-2 diabetes to a dysfunctional immune system, and researchers said these findings could lead to better drugs or perhaps even vaccines to treat the effects of both conditions.
Rates of obesity and type 2 diabetes are surging around the world as people eat more and exercise less. The four studies published in the journal Nature Medicine help explain how obesity might cause diabetes and how the two together can cause organ damage, heart disease and death.
Guo-Ping Shi at Brigham and Women's Hospital and Harvard Medical School in the United States and colleagues found that mast cells — the immune cells that get out of control in allergy and asthma — were abundant in fat tissues of obese and diabetic people and mice.
They created obese and diabetic mice by overfeeding them. Then they gave some of the mice two antihistamines, one called ketotifen fumarate, sold by Novartis AG under the brand name Zaditor and generically available cromolyn.
Both help stabilize mast cells in people with allergy or asthma, Shi said in a statement.
Mice fed a healthy diet improved moderately, while those given either cromolyn or Zaditor showed dramatic improvements. But mice given the drug and switched to a healthy diet showed nearly 100 percent recovery in all areas.
"The best thing about these drugs is that we know it's safe for people," Shi said. "The remaining question now is: Will this also work for people?"
Shi will test both in monkeys.
Type 1 diabetes is an autoimmune disease — one in which the immune system mistakenly attacks healthy tissue. The studies in Nature Medicine suggest that type 2 diabetes and obesity also involve the immune system.
Satoshi Nishimura of the University of Tokyo and colleagues found a surge in immune cells or lymphocytes called CD8 T-cells in obese mice fed a high-fat diet.
Mice engineered to be deficient in CD8 T-cells had markedly less inflammation, even when fed a high-fat diet.
"So if we can find the molecule that triggers (the production of) CD8 T-cells, we can block or inhibit it (the molecule) using drugs," Nishimura said in a telephone interview.
Harvard pathology professor Diane Mathis and colleagues found T-cells were abundant in the abdominal fat tissue of normal-weight humans and mice, but absent in obese and diabetic humans and mice.
Obese mice and people had another class of immune cells called macrophages in their fat while normal weight people and animals did not have them.
This could cause the body to stop using insulin correctly — a hallmark of type 2 diabetes, said Harvard's Steven Shoelson, who worked on the study.
"It's possible that the inflammation caused by macrophages results in insulin resistance," Shoelson said. T-cells may help control this, he said.
Michael Dosch of the Hospital for Sick Children in Toronto, Canada, and colleagues made similar findings. It may be possible to vaccinate people against type 2 diabetes, they suggested.