Tailored diet, exercise can ‘completely’ reverse liver disease with diabetes



Parks EJ. Benefits of lowering liver fat in prediabetes and diabetes. Presented at: American Diabetes Association Scientific Sessions; June 23-26, 2023; San Diego.

Parks reports no relevant financial disclosures.

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Key takeaways:

  • Insulin resistance is associated with both diabetes and nonalcoholic fatty liver disease.
  • Reducing sugar intake and increasing physical activity can reduce liver damage.

SAN DIEGO — Diabetes and nonalcoholic fatty liver disease are “common bedfellows” due to processes brought on by insulin resistance, but a reduction in dietary sugars combined with exercise can reverse the damage, according to a speaker.

Diabetes and nonalcoholic fatty liver disease (NAFLD) occur together in populations, Elizabeth Parks, PhD, FAHA, FTOS, professor of nutrition and exercise physiology at the University of Missouri School of Medicine and associate director of the Clinical Research Center in the Institute for Clinical and Translational Science, said during the Edwin Bierman Award Lecture at the American Diabetes Association Scientific Sessions.

Man exercising

Insulin resistance is associated with both diabetes and nonalcoholic fatty liver disease. Source: Adobe Stock.

“These diseases are common bedfellows because insulin resistance causes an increase in fat buildup in the liver and this causes the liver to put out more glucose into the blood, making diabetes worse,” Parks told Healio. “It is a negative circle, with the liver stuck in the middle having to deal with too many extra calories.”

However, Parks and a team of researchers, including hepatologists, exercise physiologists and registered dietitians, have conducted groundbreaking studies using stable isotope tracers and mass spectrometry to track how and where the body metabolizes dietary fats and sugars. That research has yielded discoveries in human fat metabolism that is changing the way liver disease is managed and treated.

Elizabeth Parks, PhD, FAHA, FTOS

“Our lab focuses on the transitions between fasting, to feeding, to fasting, in humans and in rodents,” Parks said during the presentation. “I believe the basis for much disease happens when the endogenous nutrients that are present in the blood and are being released stay in the blood while dietary nutrients come in, and there is a competition between those two sources of nutrients. That is the basis of most disease, and it happens when you are fed.”

Fasted vs. fed state

Many common medical tests for patients are conducted when the patient is in a fasted state, Parks said.

“It is because we think of this as a steady state of metabolism,” Parks said. “But Richard Feynman said a system is in equilibrium when all the fast things have happened but the slow things have not. This is true. The longer individuals fast, finally, their glucose comes down to a real nadir. Even in the fasting state, we are not really at a ‘steady state.’”

In past research, Parks and colleagues defined and identified the natural sugar stimulation of de novo lipogenesis in healthy people, discovered lipogenesis is elevated in people with nonalcoholic steatohepatitis, and that that biochemical pathway loses its circadian rhythm in overnutrition. Parks and colleagues have also investigated the role of insulin resistance and mitochondrial activity in NAFLD and modeled nonlinear systems to investigate muscle fatty acid uptake in insulin resistance and intestinal lipid metabolism.

“We try to focus on the transitions in protein fat and carbohydrate metabolism as we seek to study treatments that optimize these transitions in fasting and feeding to reduce burden,” Parks said.

‘The liver can heal’

Data show the more weight loss a person experiences, the greater the drop in de novo lipogenesis, Parks said. More loss of de novo lipogenesis is associated with a greater drop in liver fat. Exercise is also associated with an improvement in liver disease, Parks said, whereas a decrease in liver fat is also associated with a decrease in hepatic glucose.

The process is what Parks calls the “reroute hypothesis”: Energy restriction, through a precision diet, likely reduces the transcription factors that produce fatty acids and also deny the liver the substrate — fructose and glucose — to make fatty acids. Fitness, through exercise, reduces nutrient overload, reducing liver fat, cell death and hepatic glucose production, potentially leading to remission of liver disease.

“NAFLD is completely reversible with diet and exercise,” Parks told Healio. “Reductions in dietary sugars cause a reduction in the storage of fats in the liver from any source. Fats coming in from the diet are less likely to be stored in the liver, as are fats coming to the liver from the adipose tissue. Thus, reducing sugars in the diet signals the liver to store less fat overall.”

Like diet, exercise helps improve liver health by routing glucose and fats away from the liver to be burned in the muscle, Parks said.

“This reduces excess nutrient toxicity and without this pressure, the liver can heal,” Parks told Healio. “Thus, the two treatments, diet and exercise, work together to provide a maximal benefit to the liver.”

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