In Brief: Working To Solve a Common Weight Loss Surgery Complication
Joslin Scientists Find New Clues for Treatment
Joslin Diabetes Center researchers and Harvard Medical School colleagues have identified metabolic changes that may explain why nearly 30 percent of patients who undergo weight loss surgery develop post-bariatric hypoglycemia (PBH). This serious condition occurs when the body overproduces insulin after meals, causing dangerous blood sugar crashes after meals that can lead to confusion, fainting, and seizures.
“While some patients can manage PBH with diet and medication, severe cases don’t always respond to treatment—or even to reversing the surgery,” said co-corresponding author Mary-Elizabeth Patti, MD, Director of Joslin’s Hypoglycemia Clinic. “That’s why finding new treatment options is so important.”
Bariatric surgeries, such as gastric bypass and sleeve gastrectomy, are powerful tools for treating type 2 diabetes (T2D), a condition that affects more than 500 million people worldwide and increases the risk of heart disease, kidney failure, and nerve damage. While lifestyle changes and medications can help manage the disease, bariatric surgery has proven to be an effective intervention for T2D, triggering immediate beneficial metabolic changes that lead to improved insulin sensitivity and reduced blood sugar levels in addition to sustained weight loss. In some individuals, glucose levels can drop to levels below normal, or hypoglycemia.
In previous studies, Patti and colleagues found that patients with PBH had significantly higher levels of a hormone called FGF19 compared to post-surgical individuals without hypoglycemia. People with obesity tend to have lower levels of this hormone, but after bariatric surgery, its levels rise—sometimes too much.
To understand what triggers this spike in FGF19, Patti’s team, working with the laboratory of co-corresponding author Sloan Devlin at Harvard Medical School, analyzed bile acids—digestive compounds that help break down fats and that play a crucial role in regulating metabolism and blood sugar. Comparing samples from patients with PBH and individuals without the condition, they found distinct differences in bile acid composition, suggesting these differences may be responsible for the excessive insulin response and hypoglycemia after meals.
Through a series of experiments, the researchers mapped out the metabolic steps likely driving PBH. By identifying specific proteins involved in the process, they uncovered a potential new treatment strategy: blocking a transporter in the gut responsible for shuttling bile acids from intestines into blood. By inhibiting this transporter in mice, the researchers were able to reduce the blood sugar drop that happens after a meal. Their findings offer hope for more effective therapies to help patients struggling with unpredictable and potentially life-threatening blood sugar drops after bariatric surgery. More broadly, this work may have implications for patients struggling with hypoglycemia in other contexts. The findings appeared in Nature Metabolism.
Read the full paper in Nature Metabolism.
BIDMC Study Authors: Co-authors included Rafael Ferraz-Bannitz, Cameron Cummings, Amanda Sheehan, Pilar Casanova Querol, Berkcan Ozturk and Hanna Lang of Joslin; co-corresponding author A. Sloan, Devlin, Snehal N. Choudhari, Gabriel D’Agostino, Fei Ye of Harvard Medical School; Yingiia Chen and Eric G. Sheu of Brigham and Women’s Hospital.
COI: Dr. Patti Serves on the data safety monitoring board for Fractyl, has received investigator-initiated research support from Dexcom, and has served as a consultant for Eiger, Hanmi and MBX Pharmaceuticals.
Citation: This study was supported by grants from the National Institutes of Health (R01 DK126855, R01 DK121995, K99 DK128503, P30 DK036836); and an American Surgical Association Foundation Fellowship Award.
About Joslin Diabetes Center
Joslin Diabetes Center is world-renowned for its deep expertise in diabetes treatment and research. Part of Beth Israel Lahey Health, Joslin is dedicated to finding a cure for diabetes and ensuring that people with diabetes live long, healthy lives. We develop and disseminate innovative patient therapies and scientific discoveries throughout the world. Joslin is affiliated with Harvard Medical School and one of only 18 NIH-designated Diabetes Research Centers in the United States.
