NEW YORK – All sugars are not created equal, and the difference in the effects on the body between different types of sugar added to processed foods may explain at least some of the spike in type 2 diabetes incidence, an investigator said at the annual advanced postgraduate course held by the American Diabetes Association.

Most sweetened foods do not contain either pure fructose or pure glucose, but animal and human studies of their differential effects show that macronutrient components of diet can conspire with increased body weight and fat to cause metabolic disease, said Kimber L. Stanhope, Ph.D., associate research nutritional biologist in the department of molecular bioscience at the University of California, Davis, School of Veterinary Medicine.

Dr. Kimber L. Stanhope said various types of sugar, such as those contained in gummied fruit snacks, can increase body weight and fat to cause metabolic disease.

"Fructose compared to glucose increases visceral adiposity [and] lipid dysregulation and decreases insulin sensitivity," she said.

Both epidemiologic data and recent experimental evidence suggest that consumption of 25% of daily energy as beverages sweetened with high-fructose corn syrup (HFCS), or 12.5% of energy as sucrose-sweetened beverages can increase cardiovascular disease (CVD) risk factors in young adults in as little as 2-3 weeks, she said.

Other evidence suggests that, among middle-aged overweight or obese adults, consumption of sucrose-sweetened drinks at about 20% of energy intakes increases levels of fat in the liver and viscera and increases CVD risk factors over 6 months.

The findings also suggest that current USDA guidelines, which recommend no more than 25% of energy intake from added sugars, need to be revised to lower the acceptable upper limit for sugar, Dr. Stanhope said.

"However, obtaining absolutely definitive evidence that even the sugar industry cannot criticize will require clinical studies in which we provide every gram of food to our subjects, and that will ensure there are absolutely no confounders among the diets of the various groups that could undermine our conclusions," she said.

But even assuming that study funding is available, definitive results may not be available for another 6 or 7 years.

"Do we really want to wait that long before we do something about our dietary guidelines, or before we really start educating the public?" she added.

Different sugars, different results

Dr. Stanhope and other researchers look at fructose and glucose because both have been shown to cause metabolic dysregulation and have been implicated as contributors to metabolic disease. To tease out the possible causes, it is necessary to study their separate mechanistic effects, she said.

She and colleagues conducted a study in 2009 in which men and women aged 40-72 years were given either glucose- or fructose-sweetened beverages as part of energy-balance meals, with the sugars comprising 25% of energy requirements for 10 weeks. The subjects were in the overweight to moderately obese range, with body mass indices (BMIs) ranging from 25 to 35 kg/m².

The investigators hypothesized that fructose would lead to greater weight gain than glucose because fructose dose not stimulate production of the satiety hormone leptin, but the hypothesis was not borne out. Patients in each group gained a mean of about 1.5 kg, and an identical amount of body fat as measured by dual-energy x-ray absorptiometry (DEXA) scan.

"However, there was a surprise: the subjects consuming fructose tended to deposit the new fat that they gained in the visceral adipose, whereas the subjects consuming glucose deposited more of their new fat in the subcutaneous adipose," Dr. Stanhope said.

The mechanism for the different fat distribution may involve lipoprotein lipase (LPL), the rate-limiting enzyme that clears triglycerides from circulation and deposits them into adipose for storage or to muscle for energy use. The enzyme is activated by insulin, and LPL associated with subcutaneous fat has been shown to be much more sensitive to insulin activation than LPL associated with visceral fat.

Compared with glucose, consumption of fructose is associated with lower postmeal glucose peaks, lower postmeal insulin peaks, and lesser activation of LPL in subcutaneous fats, which therefore leaves more fat in circulation for uptake by visceral adipose tissue, Dr. Stanhope explained, noting that this model is hypothetical and needs to be confirmed with further studies.

Asked in an interview whether naturally occurring fructose was associated with similar effects to that of fructose added to processed foods, Dr. Stanhope said that fresh fruits actually contain only small amounts of fructose and have healthy components such as antioxidant compounds that far outweigh any negligible metabolic effects of fructose.

Dr. Stanhope reported having no financial disclosures.

Fructose sweeteners drive metabolic dysregulation