From the AGA Journals

Study linked gastric phenotypes, hormone levels to obesity

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Study is valuable, but needs further validation

The last 2 decades have witnessed a dramatic rise in surgical as well as less invasive procedures to combat obesity and insulin resistance. However, it is clear that bariatric medicine/surgery has a long way to go. We have little or no knowledge about predictors of outcome and optimal selection for response to medical, surgical, or endoscopic interventions, leading to a "one-size-fits-all" approach, which may not be the most appropriate for treating obesity.
Perhaps an even more important problem is that therapies (such as drugs or balloons) may be ignored or even dismissed on the basis of overall disappointing results in large cohort studies, even though they may have the potential to produce much more significant weight loss in yet to be identified subgroups of patients.

Dr. Pankaj Jay Pasricha

With the expected proliferation of less invasive procedures with better patient acceptance, it becomes even more imperative, therefore, to start phenotyping patients across several dimensions including, but not limited, to the individual's gastrointestinal physiology and pathophysiology. In this article, Acosta et al. have taken a preliminary step in that direction, with a focus on gastric physiology and associated parameters of eating and satiety in a large group of obese patients. Their initial classification of "gastric phenotypes" needs to be validated further but provides a valuable framework to start building a more nuanced and tailored approach to interventions, particularly those that act predominantly on the stomach such as balloons, a dazzling variety of which are expected to appear on the market in the near future.

Dr. Pankaj Jay Pasricha, AGAF, is director of the Johns Hopkins Center for Neurogastroenterology; director of the Food Body and Mind Center at Johns Hopkins; professor of medicine and neurosciences, Johns Hopkins School of Medicine; and professor of innovation management, Johns Hopkins Carey School of Business, Baltimore. He has no conflicts of interest.


 

References

A prospective study linked obesity to faster gastric emptying time, higher fasted stomach volume, lower postprandial levels of the appetite-modifying hormone peptide tyrosine tyrosine, and higher postprandial levels of glucagonlike peptide–1, researchers reported in the March issue of Gastroenterology.

By understanding how patients’ obesity relates to these types of specific, quantifiable measures, clinicians might better tailor treatments based on their mechanisms of action, said Dr. Andres Acosta and his associates at Mayo Medical School, Rochester, Minn. “This observation has public health relevance, as it would usher in a new era of matching patients based on quantitative traits to pharmacotherapy, potentially enhancing drug efficacy in treatment of obesity, and reducing expenditures for both validating the efficacy of such medications and prescribing them to obese individuals in clinical practice,” the researchers said.

Source: American Gastroenterological Association

Extended-release phentermine-topiramate and other prescription weight-loss therapies vary from patient to patient in terms of efficacy, the researchers noted. For example, only about half of patients treated with phentermine-topiramate ER have been found to lose more than 10% of their body weight, while 30% lose less than 5% of body weight on the drug, they said. Furthermore, past studies have yielded conflicting data on whether gastric functions, such as emptying time and volume, predict body mass index (BMI), they noted (Gastroenterology 2014 Dec. 2 [doi:10.1053/j.gastro.2014.11.020]).

To explore these relationships, the investigators prospectively studied 328 adults and found that obese individuals had higher stomach volume when fasting (P = .03), faster gastric emptying (P < .001 for solids and P < .011 for liquids), lower levels of peptide tyrosine tyrosine (PYY) after eating (P = .003), and higher postprandial levels of glucagonlike peptide–1 (GLP-1) (P < .001), compared with normal-weight individuals.

Next, they carried out an expanded analysis that added retrospective data from another 181 adults. Among the 509 total subjects in that analysis, 85 were of normal weight (BMI, 18-24.9 kg/m2), 158 were overweight (BMI, 25-29.9 kg/m2), 135 fell within the obesity class I definition (BMI, 30-34.9 kg/m2), and 131 met the criteria for obesity class II (BMI greater than 35 kg/m2), the researchers reported. This study found that obese subjects ate more before feeling full (P = .038), compared with normal-weight individuals, as did patients whose waist circumference was abnormally high (P = .016), compared with subjects of normal girth, they added. In fact, for every 5 kg per m2 increase in BMI, individuals consumed about 50 calories more, and those with abnormal waist circumference consumed about 100 calories more at a buffet meal, compared with individuals whose waist circumference was normal (P = 0.016), they added.

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The researchers also studied the effects of phentermine-topiramate ER on weight loss in 24 of the obese individuals, of whom half were randomized to the drug and half to placebo. The treatment group lost an average of 1.4 kg (standard deviation, 0.4 kg), compared with a 0.23-kg average loss for the placebo group (SD, 0.4 kg; P = 0.03), the investigators said. The treatment group also consumed fewer calories and had slower gastric emptying than the placebo group, they added. Furthermore, the amount of calories that individuals had previously consumed at a buffet meal was significantly linked with their response to phentermine-topiramate ER, they reported. Based on those results, obese individuals who tend to consume more than 1,000 calories at buffets could be expected to lose more than 1 kg per week on phentermine-topiramate ER, at least in the short term, they added.

Finally, factors related to satiety were found to explain 21% of differences among overweight and obese individuals, while gastric capacity explained 14% and psychological factors such as anxiety and depression explained 13%, the investigators said. Such measures “can serve as biomarkers to enrich selection of patients for treatment, based on the pharmacological effects of the medication,” they added. Just as satiety predicted response to phentermine-topiramate ER, other biomarkers might predict response to amylin agonists or GLP-1 agonists, they said.

The National Institutes of Health supported the study, and Vivus provided medication. The researchers reported having no conflicts of interest.

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