Several studies have linked sugar to health problems, but researchers from Yale found that sucralose, a common zero-calorie artificial sweetener, can also potentially have negative health impacts when combined with carbohydrates.

Sucralose is found in Splenda, low-cal sodas and thousands of baked and fried goods, many of which also contain carbs. A study published in the peer-reviewed journal Cell Metabolism this month found that consuming sucralose with carbohydrates could decrease the body's insulin sensitivity and the brain's response to sugar.

Because the study included a small sample size that lasted only two weeks, it's hard to say exactly what kind of long-term impact those changes could have on people's health, said senior author Dana Small, director of Yale's Modern Diet and Physiology Research Center.

"It's possible that if people kept consuming those beverages that they would adapt," Small said. "But ... in an extreme circumstance, this could contribute to the development of diabetes."

There is a theory that consuming sweet foods and beverages without calories “uncouples” sweet taste perception from energy intake, which impairs the body's response to sugar, leading to weight gain, glucose intolerance and diabetes.

To test that theory, researchers gave 45 healthy adults who did not regularly consume low-calorie sweeteners three different kinds of sweetened beverages. 

One group was given a beverage sweetened with sucralose, the equivalent of two packets of Splenda. The second group was given an equally sweet beverage with table sugar. The third group had a beverage with the artificial sweetener and a tasteless carbohydrate called maltodextrin.

Participants drank seven of these beverages over the course of two weeks, and no changes were observed in the group drinking sucralose alone or sugar. Researchers found that only when artificial sweeteners were combined with carbohydrates did the subject's insulin sensitivity and brain response to sugar become impaired, refuting the "uncoupling" theory.

To rule out the possibility that the maltodextrin was the cause, researchers performed a follow-up experiment and found no evidence that the carbohydrate alone could alter insulin sensitivity.

Small said a lot more research needs to be done to determine the long-term effects, whether they're reversible and whether they occur with other low-calorie sweeteners.

Small said that it's "probably naive" to think artificial sweeteners don't cause harm and that the negative impact is most clear when they are consumed with carbohydrates.

"I think there's growing evidence that consuming artificial sweeteners can cause harm," she said. "If you’re going to consume artificial sweetener, don’t have your diet soda with french fries. Have the diet soda by itself."