Diabetes is a disease in which the pancreas either does not produce enough insulin or cells in the body fail to respond to insulin properly. Diabetic patients experience abnormally high blood sugar levels, which can lead to heart disease, stroke, kidney failure, and eye damage. The disease, which affects more than 29 million Americans, is treated with drugs that help to keep blood sugar within a normal range. Steatosis, or fatty liver, occurs in at least half of all diabetics, though the relationship between the two diseases is not clear. Steatosis can also occur in other patients, such as those with hepatitis. It is a condition in which fat accumulates in the liver, causing inflammation and damage to liver cells. Most patients with fatty liver can only be treated with lifestyle and diet changes.

In a study published in the February issue of Diabetes, Obesity and Metabolism, scientists at Weill Cornell Medicine have identified a new drug that appears to treat both of these diseases at the same time. The drug targets a specific protein, called retinoic acid receptor beta-2 (RARB2), which is critical in the development and functioning of pancreatic cells.

"This is a whole new class of drugs," said senior author Dr. Lorraine Gudas, chair of the Department of Pharmacology and the Revlon Pharmaceutical Professor of Pharmacology and Toxicology at Weill Cornell Medicine. "RARB2 is a new target for diabetes treatment. We are also excited because, currently, there is no medicine that effectively treats fatty liver, so this may be a breakthrough therapy."

The researchers studied mice with diabetes. The mice were given the new drug in their water. "We found that this drug restored normal blood sugar levels in the mice," said Dr. Xiao-Han Tang, an assistant research professor in pharmacology at Weill Cornell Medicine, who is an author on the paper. "And we also found that it reduced fatty liver symptoms."

The new drug, which has not been tested in humans, might have several advantages over current treatments. First, it is able to be taken orally, which makes it appealing for patients when compared to injectable diabetes medications. Second, it does not cause weight gain in mice. This is critical, said first author Dr. Steven Trasino, a postdoctoral fellow in pharmacology at Weill Cornell Medicine. "Some of the most commonly used anti-diabetes drugs cause weight gain, which can eventually make both diabetes and fatty liver worse. Avoiding that is a great advantage."

The ability to treat both of these diseases at once could result in major benefits to patients. "We think that this drug is a potential, potent anti-diabetic drug for humans," Dr. Tang said. "It's very exciting." Dr. Gudas and her team, which also includes Dr. Jose Jessurun, a professor of pathology and laboratory medicine and co-author of the paper, are making plans to bring this discovery to the clinic.

Eating protein and vegetables before carbohydrates leads to lower post-meal glucose and insulin levels in obese patients with type 2 diabetes, Weill Cornell Medical College researchers found in a new study. This finding, published June 23 in the journal Diabetes Care, might impact the way clinicians advise diabetic patients and other high-risk individuals to eat, focusing not only on how much, but also on when carbohydrates are consumed.

]"We're always looking for ways to help people with diabetes lower their blood sugar," said senior author Dr. Louis Aronne, the Sanford I. Weill Professor of Metabolic Research and a professor of clinical medicine at Weill Cornell Medical College, who is the study's principal investigator. "We rely on medicine, but diet is an important part of this process, too. Unfortunately, we've found that it's difficult to get people to change their eating habits.

"Carbohydrates raise blood sugar, but if you tell someone not to eat them — or to drastically cut back — it's hard for them to comply," added Dr. Aronne, who is also director of the Comprehensive Weight Control Center at Weill Cornell. "This study points to an easier way that patients might lower their blood sugar and insulin levels."

Patients with type 2 diabetes typically use a finger prick test to check their glucose levels throughout the day. Maintaining normal levels, specifically after meals, is of the utmost importance, because if a diabetics' blood sugar level is consistently high or frequently spikes, they risk complications of their disease, including hardening of the arteries and eventually death from heart disease.

This study looked to validate and advance previous research that showed eating vegetables or protein before carbohydrates leads to lower post-meal glucose levels. This time, though, investigators looked at a whole, typically Western meal, with a good mix of vegetables, protein, carbohydrates and fat.

They worked with 11 patients, all of who had obesity and type 2 diabetes and take an oral drug that helps control glucose levels, called metformin. To see how food order impacted post-meal glucose levels, they had the patients eat a meal, consisting of carbohydrates (ciabatta bread and orange juice), protein, vegetables and fat (chicken breast, lettuce and tomato salad with low-fat dressing and steamed broccoli with butter) twice, on separate days a week apart.

Dr. Louis Aronne. Photo credit: Carlos Rene Perez

On the day of their first meal, researchers collected a fasting glucose level in the morning, 12 hours after the patients last ate. They were then instructed to eat their carbohydrates first, followed 15 minutes later by the protein, vegetables and fat. After they finished eating, researchers checked their post-meal glucose levels via blood test at 30, 60 and 120-minute intervals. A week later, researchers again checked patients' fasting glucose levels, and then had them eat the same meal, but with the food order reversed: protein, vegetables and fat first, followed 15 minutes later by the carbohydrates. The same post-meal glucose levels were then collected.

The results showed that glucose levels were much lower at the 30, 60 and 120 minute checks — by about 29 percent, 37 percent and 17 percent, respectively — when vegetables and protein were eaten before the carbohydrates. Insulin was also significantly lower when protein and vegetables were eaten first. This finding confirms that the order in which we eat food matters, and points to a new way to effectively control post-meal glucose levels in diabetic patients.

"Based on this finding, instead of saying ‘don't eat that' to their patients, clinicians might instead say, ‘eat this before that,'" Dr. Aronne said. "While we need to do some follow-up work, based on this finding, patients with type 2 might be able to make a simple change to lower their blood sugar throughout the day, decrease how much insulin they need to take, and potentially have a long-lasting, positive impact on their health."