Diabetes Forecast

Can Low-Calorie Sweeteners Contribute to Diabetes?

M. Yanina Pepino, PhD
News Bureau/Fred Zwicky

M. Yanina Pepino, PhD

Sensory nutrition scientist at the University of Illinois


American Diabetes Association Research Funding
Innovative Research

In an effort to cut sugar without cutting sweet taste, people with diabetes often become heavy consumers of artificial sweeteners. Products such as aspartame, saccharin, and sucralose are part of a $3 billion industry, used to flavor a wide variety of products by replacing sugar in everything from diet sodas to cookies and yogurt.

For most people, drinking sugar-free soda or eating an artificially sweetened cookie is based on a straightforward assumption that sugar substitutes don’t do anything but add flavor—they’re “free.” As far as the body is concerned, in other words, liquid containing a no-calorie sweetener should be the same as water, but better (or at least sweeter) tasting.

But what if low- and no-calorie sweeteners play a role in promoting diabetes? In a long-term study of more than 750 people over age 65, heavy consumption of low-calorie sweeteners—the equivalent of three or more diet sodas a day—was associated with weight gain and higher rates of type 2 diabetes and heart disease.

University of Illinois sensory nutritionist M. Yanina Pepino, PhD, is investigating what might be going on with the help of a grant from the American Diabetes Association. An expert on taste and metabolism who’s spent more than a decade exploring the science of artificial sweeteners, Pepino admits the science is new—and confusing. “There’s a lot of paradoxical data,” she says.

For example, perhaps people who are overweight and therefore at a higher-than-average risk of developing type 2 diabetes are more likely to be consuming artificial sweeteners in an effort to reduce their calorie intake. That doesn’t necessarily mean diet soda caused their diabetes.

Pepino’s research suggests there might be something else at play. Sweet taste, not sugar itself, may tamp down the body’s response to insulin. When this happens, the cells don’t take up glucose from the blood like they should, a condition known as insulin resistance. It’s a known contributor to type 2 diabetes, along with the higher insulin production that usually follows.

To test her theory, Pepino gave 17 obese people a calorie-free drink containing sucralose, a common sweetener sold under the Splenda brand name that is 600 times sweeter than sugar. (The drink was formulated to be a little sweeter than the typical diet soda.) Afterward, she monitored how their bodies reacted to an oral glucose tolerance test, a common measure of how well the body handles glucose.

Pepino then repeated the whole procedure, but this time she gave the subjects plain water to drink before the glucose test. “If the artificial sweetener is really inert, then the [body’s glucose response] should be the same as if you drink water,” she says. “But we found it was not the same.” Instead, the glucose tolerance test showed that the participants in the study were more insulin resistant after the sucralose drink than after water.

Her early data also suggests that there may be sweet taste receptors in the intestine that affect blood glucose. In a recent experiment, she asked participants to spit the sucralose drink out to see if just having the sweet taste would be enough to trigger a different response to the glucose test. This time, participants’ insulin levels didn’t rise as high as when the drink was swallowed, indicating less insulin resistance. This suggests the intriguing possibility that sweet taste signaling in the gut and the mouth independently regulate blood glucose.

In her latest experiment, Pepino is investigating hard-core artificial sweetener users to see if their reactions are different from those who don’t consume sugar substitutes regularly. In her earlier experiments, she tested the reactions of people who didn’t use artificial sweeteners regularly. This time, 20 volunteers who regularly consume artificial sweeteners and 20 who don’t will repeat the study to see if regular use changes the body’s response to the sweet taste and reduces the insulin resistance. “Perhaps if you use artificial sweeteners a lot, the brain doesn’t use sweetness signaling effectively,” she says.

It’s all part of an ongoing effort to figure out how these common food additives are affecting the body. Pepino is careful to stress that she doesn’t know for sure what’s going on, or whether all sugar substitutes cause the same responses as sucralose. But she is convinced that modern life is way too sweet. Readily available sweet flavors are a new phenomenon in the human experience: For our not-so-distant ancestors, sweetness would have been a rare treat, gleaned from ripe fruit or the very occasional raid on a beehive.

That suggests the importance of recalculating our relationship not just with sugar, but with sweet tastes altogether. “People should consume sweetness in moderation,” says Pepino. “It should be a treat, not a daily, constant occurrence.” 

Help Support Diabetes Science

If you would like to support diabetes research, such as that being done by M. Yanina Pepino, PhD, please go to diabetes.org/researchdonation.


Learn how estate and trust gifts made to the American Diabetes Association can change the future of diabetes. Call 888-700-7029 or e-mail plannedgiving@diabetes.org for more information.



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