Some people don't like to eat their vegetables, but for obese people with type 2 diabetes, broccoli could hold the key to slowing, and potentially reversing, the disease, according to a new study.
Scientists used both computational and experimental research to zero in on a network of 50 genes that cause symptoms associated with type 2 diabetes. They also located a compound called sulforaphane - which is found naturally in cruciferous vegetables such as broccoli, Brussels sprouts and cabbages - that could turn down the expression of those genes, according to the findings, published today (June 14) in the journal Science Translational Medicine.
In the study, the scientists gave sulforaphane to obese patients, in the form of a concentrated broccoli sprout extract. They found that it improved the patients' systems' ability to control their glucose levels and reduced their glucose production - two symptoms of diabetes that can lead to other health problems, including coronary artery disease, nerve damage and blindness, according to the Centers for Disease Control and Prevention.
"It's very exciting and opens up new possibilities for the treatment of type 2 diabetes," Anders Rosengren, an assistant professor at the University of Gothenburg in Sweden, told Live Science.
Type 2 diabetes, the most common form of diabetes, affects more than 300 million people globally. For those with the disease who are obese, the excess fat in the liver makes the body less sensitive to the hormone insulin, which can make it difficult for the organ to help regulate blood sugar levels. Normally, insulin, which is produced by the pancreas, stimulates the liver to pull glucose out of the bloodstream and store it for later use.
People with type 2 diabetes are usually advised to change their diet to help control their blood sugar levels. "Lifestyle changes are at the core of type 2 diabetes treatment but often need to be complemented with drugs," Rosengren said.
Currently the main treatment option is the drug metformin. But not every person who needs it can take it. About 15 percent of type 2 diabetes patients have reduced kidney function and taking metformin can increase their risk for lactic acidosis, an unhealthy build-up of lactic acid, which can cause abdominal discomfort, shallow breathing, muscle pain or cramping, and tiredness.
About 30 percent of patients who take metformin develop nausea, bloating and abdominal pain.
Finding an alternative to metformin was one of the team's objectives. But there was also general frustration in the clinical community that research labs were having a difficult time developing new anti-diabetic compounds, Rosengren said.
One challenge is that researcherslooking to develop new drugs have traditionally studied single genes or individual proteins. But diabetes is much more complicated than that. It involves a large network of genes, so the scientists had to find a new, systematic approach that took a holistic view of the disease.
Study leader Annika Axelsson, a doctoral student at Gothenburg, and her colleagues began by analyzing liver tissue from diabetic mice who were raised on a "Western diet" containing 42 percent fat and 0.15 percent cholesterol. After several tests, the scientists identified 1,720 genes associated with hyperglycemia, a condition in which an excessive amount of glucose circulates in the blood.
After further analysis, the researchers narrowed the 1,720 genes to a network of 50 linked genes that together result in high bloodglucose levels. This network became the so-called disease signature for type 2 diabetes.
Next, the researchers used a database of existing drug compounds and employed a mathematical modeling program to rank those compounds for their potential ability to reverse the disease signature - in other words, to turn down those overexpressed genes.
Sulforaphane had the highest ranking. The team ran several experiments to see if it could actually lower glucose levels in living systems. First, they tested the compound in cells growing in lab dishes, and found that it inhibited glucose production. Next, they tested it in rodents, and found that it improved glucose tolerance in animals on a high-fat or high-fructose diet.
Finally, the researchers tested sulforaphane in people. Over the course of 12 weeks, 97 patients with type 2 diabetes took a daily dose of concentrated broccoli sprout extract in powdered form. The dose was about 100 times the amount found naturally in broccoli. For those who were not obese, the sulforaphane did not have any affect.
But for those who were obese, the results were significant, the researchers reported. Typically, for people with type 2 diabetes, glucose levels in the blood stay high, even when they are fasting. But sulforaphane reduced fasting blood glucose in these patients by 10 percent compared to the participants in the study who took a placebo, according to the study. That amount is enough to lower a person's risk of developing health complications. And the compound did not cause gastrointestinal problems that metformin can cause, nor other side effects.
For the next phase of this study, Rosengren said the team would like to investigate the effects of sulforaphane on people with prediabetes to see whether it could improve their glucose control before type 2 diabetes develops.
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