Obesity Type Factors Into Weight Loss Success

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MAUI, Hawaii — When the correct obesity treatment is matched with the right patient, weight loss can double, said Andres Acosta, MD, PhD, from the Precision Medicine for Obesity Lab at the Mayo Clinic in Rochester, Minnesota.

Understanding what is driving each patient’s weight gain will be key to turning around the grim projection that obesity rates in the United States will approach 50% by 2030, he said here at the Gastroenterology Updates IBD Liver Disease Conference 2020.

His team is trying to understand why some people succeed with only lifestyle changes and other people gain weight even after bariatric surgery. Identifying the underlying cause of obesity is becoming crucial as the list of treatment options grows.

Acosta and his team invited patients at Mayo to participate in the study via ads and fliers. They included 600 patients with a body mass index greater than 30 kg/m2 and no other obesity-related comorbidities. The researchers then used a machine-learning algorithm based on measurements of calories consumed, energy burned at rest, and emptying of food from the stomach; they also employed questionnaires on eating, exercise habits, and emotional status. The patients were then classified into four phenotypes:

“When these patients start eating, they go for seconds and thirds and don’t feel full. They usually don’t feel hungry, but once they start eating, they cannot stop.”

“These folks eat to normal fullness and within an hour or two they start feeling hungry again. The gut is not giving the signal to the brain.”

Emotional hunger

“They eat for reward and sensations. Some call this ‘food addiction.’ “

Slow burn

“These patients have a faulty metabolism and aren’t burning calories efficiently.”

When the researchers tested the prevalence of the four phenotypes in a different cohort of 180 Mayo patients, recruited in the same way as the previous cohort, they found that 25% fit into more than one phenotype category and 9% fit into none of the categories.

These cohorts reflect the general obese population in the United States, Acosta told Medscape Medical News. And “we know that there might be more phenotypes — this is a new way of classifying obesity.”

This is a new way of classifying obesity.
Dr Andres Acosta

The phenotypes that the researchers identified help to show how patients in each group differ from the general obese population, he added. For instance, when Mayo researchers presented patients with a buffet-style meal where they could eat until they felt full, they found that women who are obese generally eat about 700 calories. But women with a ‘hungry brain’ phenotype eat about 1100 calories before they feel full, he reported. For men who are obese, those thresholds are 900 and 1600 calories, respectively.

That’s quite a difference when you consider the extra calories at every meal, said Acosta.

“For those of you thinking that obesity is a behavioral disease, I’ll say sure, but only in a subset of patients” — those in the ’emotional hunger’ phenotype group, he added.

Similarly, there is a subset of patients who have abnormal, inefficient energy expenditure, the researchers found.

When a patient comes in saying the reason he weighs 450 pounds is that he has a poor metabolism, Acosta said that, instead of rejecting that notion out of hand, phenotyping can help determine when that line of thinking is worth pursuing.

“We can bring a precision medicine approach to obesity,” he pointed out.

A blood test designed to help determine phenotype is being developed by Acosta’s lab at the Mayo Clinic in conjunction with Phenomix Sciences, which Acosta founded and holds stock in.

The blood test is currently undergoing external validation, but he said he expects it to be commercially available this summer.

Phenotype-Guided Treatment

The researchers tested weight loss in two groups of patients treated with anti-obesity medication: 75 received phenotype-guided therapy; and 200 received therapy not guided by phenotype.

The groups were similar except that patients in the nonphenotype group were a bit older. Use of medications was the same, both groups had comorbidities and, in both groups, more than 40% of patients had diabetes.

However, more patients in the phenotype group than in the nonphenotype group lost more than 20% of their body weight (37% vs 1%), which is “as good as bariatric surgery at 1 year,” Acosta reported. And more patients in the phenotype group lost more than 10% of their body weight (42% vs 18%).

“A phenotype-guided intervention can really select the best responders and move the response rate from 35% to 80%,” he said. “This results in a significant weight loss, with patients going from 8% total body weight loss in 1 year to 16% total body weight loss in 1 year.”

“Just by selecting the right patient for the right intervention” — without a new medication or device — “we can double the amount of weight loss,” he explained.

Final results of the study will be presented at the Digestive Disease Week annual meeting in May, Acosta said.

POWER Program

Whereas phenotyping helps identify which patients might benefit most from which treatment, another project Acosta led lays out a continuum of care. The white paperPractice Guide on Obesity and Weight Management, Education and Resources (POWER) — developed by the American Gastroenterological Association with input from nine medical societies has four parts: assessment, intensive weight loss intervention, weight stabilization and re-intensification when needed, and prevention of weight regain.

The purpose of the POWER program is to provide personalized care through multidisciplinary teams with long-term plans for weight management that incorporate existing guidelines and tools, Acosta explained.

POWER starts with personalized assessment, and the first step is to ask patients whether they want to talk about obesity, he told Medscape Medical News.

“If they’re not ready, put it aside. If you try to talk about obesity and weight management with a patient who is not ready, you’re going to get burned; the patient will not be happy,” he said.

On the next visit, ask how he or she feels about progress made and remind the patient that weight loss is an option that can be discussed, he advised.

For patients who are ready, the POWER program lays out nutrition and physical activity goals.

Patients with obesity have been told they need to lose weight “multiple, multiple times,” said Laura Kulik, MD, from the Feinberg School of Medicine in Chicago, Illinois.

The approach described by Acosta — which sets out a clear plan and breaks the challenge down by giving specific patient goals for eating, calorie targets, and the number of steps they need to walk (asking them to come back if that’s not working) — shows promise, Kulik told Medscape Medical News.

“When patients don’t have a plan, I think they lose hope,” she said.

Obesity is following other diseases into personalized medicine, she pointed out, and Acosta’s phenotyping works on the same principle as figuring out the role of the ‘hunger hormone’ ghrelin and how it affects weight individually in people who undergo a gastric sleeve procedure as opposed to the gastric band.

“It’s a matter of finding how you determine that biomarker you can use to then treat each person individually,” she said.

Gastroenterology Updates IBD Liver Disease (GUILD) Conference 2020: Presented February 19, 2020.

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