MADRID — Diet is, to a certain extent, the common thread tying type 2 diabetes to fatty liver disease. And, as affirmed during the 34th National Conference of the Spanish Diabetes Society, there is mounting evidence that the increase in consumption of ultraprocessed foods is related to this link.

According to experts participating in a roundtable discussion, the data leave no question as to why metabolic-associated fatty liver disease is a significant cause for concern among endocrinologists in Spain. It is highly prevalent, and rates are trending upward. The roundtable discussion was organized by the Spanish Society of Obesity, the Spanish Society of Endocrinology and Nutrition, and the Spanish Diabetes Society.

“Metabolic-associated fatty liver disease has become the most common cause of chronic liver disease, and it is estimated that 25% of the world’s population suffers from it. However, the worst is yet to come, since it’s estimated that cases will increase by 56% over the next 10 years, which could potentially make it the leading cause of cirrhosis,” said Rubén Nogueiras, MD, of the Research Center for Molecular Medicine and Chronic Diseases of the University of Santiago de Compostela, who is a researcher with the Spanish Biomedical Research Center for Physiopathology of Obesity and Nutrition.

“Metabolic-associated fatty liver disease is caused by multiple factors,” Nogueiras told Medscape Spanish Edition. “The most common causes responsible for the growing number of cases include excess weight, obesity, insulin resistance or type 2 diabetes, abnormal levels of triglycerides and cholesterol, and metabolic syndrome, or having one or more characteristics of this syndrome. Genetic causes also come into play. Having any one of these conditions increases the likelihood of developing metabolic-associated fatty liver disease.”

The concern regarding the incidence of this disease appears to be somewhat mitigated by advances in two main areas: diagnosis, and basic and clinical research.

“Until recently, reliable diagnosis required a biopsy. However, ultrasound technology is now available that can measure liver stiffness, hardness, and fatty changes within the liver. This technique, along with a blood test, allows for a relatively reliable diagnosis of the stage of the disease,” said Nogueiras.

Nogueiras pointed out that most studies focus on hepatocytes, which are the most abundant cells in the liver. “We believe that other cells may also be significant and may provide solutions for keeping the disease from progressing to more serious stages, and even for improving the condition.”

Nogueiras and his team focus their efforts on studying stellate cell reprogramming. Normally inactive, stellate cells are activated when the liver is injured and are responsible for the hepatic fibrosis that develops when metabolic-associated fatty liver disease progresses, causing more serious injury.

“Depending on the type of reprogramming, we are able to activate or deactivate these cells and thereby induce or reverse hepatic fibrosis in animal models,” he said.

Medicinal Therapy

Commenting on the main areas that are currently under investigation in this disease, Nogueiras said that many groups focus their research on multiple primary goals. “One of these is to find reliable markers that can predict disease progression and classify patients using biomarkers, since not everyone with metabolic-associated fatty liver disease is the same or responds in the same way to treatment. Different clinical trials have also been performed with different drugs, and looking farther to the future, there is an effort to discover new molecules that could be used as therapeutic targets. Another aim is to find the most appropriate drug for each therapeutic target: in other words, using personalized medicine.”

The specialists agreed that despite this progress, the great, unresolved issue in the approach to metabolic-associated fatty liver disease is finding an effective medicinal treatment, since “there is currently no drug approved for treating this disease. There have been clinical trials that have tested different drugs against different therapeutic targets, but they haven’t advanced to the marketing stage,” said Nogueiras.

When asked about the outlook for discovering a medical treatment in the middle to long term, Nogueiras said, “That’s the million-dollar question. It’s a highly complex disease, and, like we said, it has many factors. That’s why finding an effective drug with few side effects is a real challenge. Up until now, the clinical trials for different drugs — of which some have appeared to be quite promising — have, for multiple reasons, not achieved the level of success we hoped. We’ll have to wait for results from ongoing studies. But we predict that in the medium term, we will find an option that will work in at least a sizeable percentage of patients.”

Ultraprocessed Foods

Nonalcoholic fatty liver disease was the theme at the plenary session that capped off the meetings. The plenary session was led by the nutritionist Shira Zelber-Sagim, PhD, of the School of Public Health at the University of Haifa in Israel.

Zelber-Sagim discussed how the types of foods that are routinely consumed affect the risks for developing nonalcoholic fatty liver disease and type 2 diabetes. She reported the latest evidence of the close relationship between both diseases. “The most beneficial treatment for nonalcoholic fatty liver disease is weight loss achieved through a Mediterranean diet paired with physical activity. So, people with this disease should eat a healthy diet that includes minimally processed or unprocessed products (fruits, vegetables, pulses, whole grains, unprocessed meats and fish, et cetera), low in sugar and saturated fat and high in polyphenols, vitamins, healthy oils (like olive oil), and some types of fats (like omega-3 fatty acids).”

The nutritionist also emphasized that the Mediterranean diet encompasses all these factors. “It has been shown that even partial adherence to a Mediterranean diet can be beneficial.”

Among the global population, however, exposure to ultraprocessed industrialized foods has “caused the Mediterranean diet to be abandoned and encouraged the adoption of a less healthy diet.”

Research such as that conducted by the European Prospective Investigation into Cancer and Nutrition, which was performed in 10 countries and included 36,034 individuals aged 35 to 74 years, has shown a “dramatic” increase in the consumption of ultraprocessed foods worldwide. According to the study, these foods represent between 61% (Spain) and 78% to 79% (the Netherlands and Germany) of average calorie intake.

Moreover, ultraprocessed foods made up 57.5% of the calories in the daily energy intake of the 9317 participants in the NHANES 2009–2010 study in the United States.

“Soft drinks, packaged snacks, breakfast cereals, instant sauces, and many oven-ready products are your typical ultraprocessed foods,” said Zelber-Sagim.

Dose-Dependent Effect

Zelber-Sagim explained that several studies carried out in diverse populations have shown an association between the proportion of ultraprocessed foods in the diet and the risk of developing diet-related chronic diseases, such as obesity and cancer, as well as gastrointestinal disorders, cardiovascular risk factors, fragility, and mortality.

“Therefore, cutting back on how much of these foods we’re eating may be an effective strategy for preventing and treating obesity and other associated diseases, like diabetes and nonalcoholic fatty liver disease,” she said.

She emphasized that a growing number of researchers have shown a direct and dose-dependent association between eating ultraprocessed foods and developing nonalcoholic fatty liver disease.

“A link between red meat and processed meat and this disease has also been observed. Also, eating too many processed foods with high fat, sugar, and fructose content and foods prepared at high temperatures leads to a higher intake of advanced glycation end products, which accelerate liver injury.”

The specialist also mentioned other factors tied to the association between nonalcoholic fatty liver disease and the consumption of ultraprocessed foods that could be leading to an increase in prevalence. “Low income and dietary deficiencies may be related to a higher prevalence of nonalcoholic fatty liver disease and advanced fibrosis, very likely due to the affordability of high-calorie processed foods that are very rich in fats and sugars, as well as a general decline in high-quality diets.

“In light of these data, the authorities need to make a pointed effort to take educational and political steps to increase the access of the general population to healthier options and to help reduce the consumption of ultraprocessed foods, not only to prevent nonalcoholic fatty liver disease and diabetes but to improve health in general,” she said.

“We need to stand up to ultraprocessed products. They are made from industrial ingredients and contain little or no whole food. So, from their very nature, they’re not healthy and should be avoided. They are also often characterized by a lower nutritional quality and a high-calorie density and contain additives, substances from the packaging that comes in contact with the foods, and compounds formed during production, processing, and storage,” she concluded.

Nogueiras and Zelber-Sagim have disclosed no relevant financial relationships.

This article was translated from the Medscape Spanish Edition.

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