CHICAGO – Of medical and surgical tactics to tackle long-term weight loss, , and gene expression in the Roux limb may hold the key to the surgery’s efficacy, according to an ongoing study.
“We know that Roux-en-Y gastric bypass surgery is highly effective as not only a weight-loss therapy, but more and more we’re appreciating its role as a diabetes therapy as well,” said Margaret Stefater, MD, PhD, speaking in an interview at the annual meeting of the Endocrine Society.
The study, she said, was designed to learn more about the intestine’s contribution to the salubrious effect that Roux-en-Y surgery has on diabetes.
“We used microarray in order to characterize gene expression in the intestine” to gain a broad understanding of the processes that are altered after surgery, said Dr. Stefater, a pediatric endocrinology fellow at Boston Children’s Hospital. More specifically, though, the study looked at an individual’s changes in gene expression over time and correlated those changes with that patient’s clinical picture.
The data reported by Dr. Stefater and shared in a press conference, represent part of an ongoing longitudinal prospective study of 32 patients.
“The study aims to characterize gene expression for the first postoperative year,” and findings from the first 6 postoperative months of 19 patients were shared at the meeting, said Dr. Stefater. “This is the first look at our cohort.”
So far, she and her colleagues have compared gene expression using microarray at 1 month and 6 months post-surgery, comparing change across time and change from baseline data.
From hundreds of candidate genes, Dr. Stefater and her colleagues have developed a smaller gene list that, even in the first postoperative month, is predictive of changes in hemoglobin A1c levels over time. “Remarkably, the changes in a select list of genes out to 1 month is actually able to predict hemoglobin A1c levels out to 1 year,” she said. “This speaks to the fact that biological reprogramming in the intestine is somehow related to glycemic response in patients.
“We hope that by understanding these processes, we can home in on those processes that are most likely to be mechanistically responsible for these changes, and then to reverse-engineer this surgery to identify processes or targets which may be good places to start when we think about creating better, or nonsurgical, therapies for people who have obesity and diabetes,” said Dr. Stefater.
Dr. Stefater reported no relevant financial disclosures.
SOURCE: Stefater MA et al. ENDO 2018, Abstract OR 12-6.