Diabetes is a metabolic disease. And while a growing list of pharmacologic agents can help treat some of the symptoms caused by altered metabolism, it may be more effective to correct the metabolic errors underlying diabetes than to treat its symptoms. That means working with the gut, the most important metabolic organ in the body.

ADAMeetingNews.org spoke with two presenters who will be discussing the latest findings on gut metabolism during Tuesday’s symposium Go With Your Gut—Intestinal Regulation of Metabolism, which will begin at 7:30 a.m. in S-208 (South, Level 2).

What does the gut have to do with diabetes?

Suzanne Devkota, PhD, Assistant Professor and Director of Microbiome Research at the F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute at Cedars-Sinai Medical Center: The gut, and the microbiome that resides within the gut, sees everything you put in your mouth. Clinicians talk about the liver seeing everything you eat, but the gastrointestinal tract sees it before the liver. Therefore, the gut sits at the intersection of inflammation, the microbiome, and metabolic disease.

What does that intersection mean for diabetes?

Dr. Devkota: We know from twin studies that the gut microbiome is intimately associated with obesity, diabetes, and other metabolic disorders. We also know that certain members of the gut microbiome are associated with glycemic response to certain foods. That suggests that it may be possible to change your glycemic response to food by altering your gut microbiome. The gut microbiome offers a new door to understand some of the pathogenesis of diabetes and other metabolic diseases, and to alter their development. 

David Mangelsdorf, PhD, Professor and the Alfred G. Gilman Distinguished Chair in Pharmacology and the Raymond and Ellen Willie Distinguished Chair in Molecular Neuropharmacology in Honor of Harold B. Crasilneck, PhD, at the University of Texas Southwestern Medical School: Patients with chronic pancreatitis can also have chronic problems secreting insulin. When the exocrine pancreas shuts down during pancreatitis, it also shuts down beta cells. In severe pancreatitis, where the exocrine pancreas dissolves itself, it also dissolves beta cells, reducing insulin secretion permanently. We have discovered a novel hormone that stops pancreatitis cold in our animal models. If it works in humans, we can both prevent pancreatitis from happening and treat it once it begins, which would make a huge difference to patients with diabetes related to their pancreatitis.

How close to clinical reality are gut-based interventions for diabetes?

Dr. Mangelsdorf: We have shown in the mouse model when squirting this novel hormone into the pancreas that you can completely eliminate pancreatitis and the diabetes associated with pancreatitis. That is an immediate indication if we can get this into clinical trials and see if it works as well in humans as it does in mice.

Dr. Devkota: We don’t yet know cause and effect in the gut microbiome, but there are aspects that clearly make the microbiome a key player in metabolism and immunity. Clinical applications are still in development, but the data we have to date suggest that when people come into a medical visit and get a blood panel in the future, they will also be getting a fecal panel. Their microbiome profile will be as much a part of their medical record as their blood glucose profile, and just as important in guiding clinical treatment choices.