June 16, 2023
An alarming increase in the prevalence of obesity, diabetes and other metabolic diseases has occurred over the past few decades. Within the United States, obesity currently affects more than 30% of the adult population. And this trend also is associated with significant economic and health care system burdens around the world.
In an article published in Gut in 2023, co-authors Michael Camilleri, M.D., D.Sc., and Emad M. El-Omar, M.D., present 10 scenarios commonly encountered by gastroenterology and hepatology clinicians in which obesity is a significant cofactor, either in the etiology or in the response to treatment of the gastrointestinal or liver disease. Dr. Camilleri is a gastroenterologist and researcher at Mayo Clinic in Rochester, Minnesota, whose clinical practice and research focus includes obesity and disorders of gastrointestinal motility and function. Dr. El-Omar is editor-in-chief of Gut.
In this Q&A, Dr. Camilleri discusses the interplay between gastrointestinal and liver diseases and obesity, while highlighting the emerging role for gastroenterologists in treating these conditions.
Your article discusses several interventions currently used by gastroenterologists to treat GI structure, incretins and metabolic function. How can gastroenterologists use this knowledge to address underlying obesity?
Gastroenterologists currently prescribe a variety of interventions to treat GI problems that also can be used to treat obesity and improve glycemic control. The list includes the use of pancreatic lipase inhibition with orlistat, bariatric endoscopy, bariatric surgery, and combination therapies targeting metabolic and GI mechanisms.
Incretin-modifying agents, including glucagon-like peptide-1 (GLP-1) receptor agonists, are emerging as the most promising drug treatments for obesity itself and nonalcoholic fatty liver disease (NAFLD). These agents also appear to provide an effective way to target central appetite mechanisms. They also slow gastric emptying, and this helps increase postprandial fullness and decrease appetite. Meta-analyses suggest that the GLP-1 agents SQ semaglutide and liraglutide perform well in this role. GLP-1 agonists are associated with an increased risk of biliary tract and gallbladder diseases, so it's necessary to watch for adverse effects. A dual incretin agonist (GLP-1/glucose-dependent insulinotropic peptide) tirzepatide also is efficacious in treating obesity, improving glycemic control and reducing liver fat content.
Researchers have demonstrated the ability of other dual incretin agonists, such as cotadutide and pemvidutide, to reduce significant hepatic fibrosis in both animal models and humans. But these agents have not yet been approved for this use in the clinical setting.
How does obesity impact treatment and complications of inflammatory bowel disease (IBD)?
Obesity may significantly impact the treatment and complications of IBD in several ways. Research has shown us that obesity increases likelihood of nonresponse to treatment with tumor necrosis factor α (TNFα) inhibitors, a staple in the treatment of IBD and other inflammatory diseases.
We also have learned that fat distribution can affect an individual's responsiveness to treatment with biological agents. In patients with Crohn's disease treated with infliximab, for example, there is a significant association between visceral, but not subcutaneous, fat adiposity and the degree of mucosal healing. Research findings demonstrating this association suggest that we need to modify doses or measure blood levels of the biological agent when possible.
Obesity does not appear to be a significant risk factor for additional risks in patients with IBD, such as the need for hospitalization, surgery and onset of serious infections. However, researchers have noted that obesity is associated with worse outcomes for ileal pouch-anal anastomosis in patients with ulcerative colitis. Overall, bariatric surgery is a safe and effective option for patients with IBD.
How does obesity impact patients with both IBD and liver disease?
Obesity may impact more than one gastrointestinal or liver disease in a single patient. A systematic review and meta-analysis demonstrated that the prevalence of both NAFLD and liver fibrosis was nearly twice as high in individuals with IBD as in healthy individuals. Body mass index was the factor most strongly associated with elevated risks of both NAFLD and liver fibrosis in individuals with IBD.
What do we know about the safety and efficacy of bariatric surgery in obese patients who also require liver transplantation?
Numerous studies have demonstrated that bariatric surgery can be performed safely in patients undergoing liver transplantation, and this combined treatment results in improvement of obesity-related comorbidities in liver transplant recipients.
What light does recent research shed on the relationship between obesity, the gut microbiome, glucose tolerance and the role of gastroenterologists in delivering these interventions?
We understand that the gut microbiome affects body weight in multiple ways. It modulates metabolism, appetite, bile acid metabolism, and the hormonal and immune systems. Researchers are studying various methods of manipulating the microbiome, including fecal microbiota transplantation (FMT), to determine their effects on glucose tolerance and obesity.
FMT may impact incretin signaling, metabolism, bile acid dehydroxylation or weight loss. Study findings suggest that FMT boosts gut bacterial bile acid metabolism and delays the onset of glucose tolerance impairment among patients who are obese but otherwise metabolically healthy.
We believe that efforts to optimize the delivery of FMT and other interventions to address obesity by manipulating the gut microbiome should be led by a multidisciplinary team that includes a gastroenterologist and hepatologist.
For more information
Camilleri M, et al. Ten reasons gastroenterologists and hepatologists should be treating obesity. Gut. In press.
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