A pathway involved in the production of bile acids may play a role in the remission of type 2 diabetes often seen after bariatric surgery. Note that serum fibroblast growth factor 19 levels increased for the majority of all groups of patients following bariatric surgery, but diabetic patients who went into remission had the greatest increases.
CHICAGO — A pathway involved in the production of bile acids may play a role in the remission of type 2 diabetes often seen after bariatric surgery, researchers reported here.
In an analysis of data from two cohort studies, diabetic patients who went into remission following Roux-en-Y gastric bypass (RYGB) surgery had the greatest increases in levels of fibroblast growth factor 19 (FGF19) and the greatest increases in total bile acids compared with diabetics who did not go into remission and with non-diabetic patients who had surgery (P<0.001 for both), according to George Argyropoulos, PhD, of Geisinger Health System in Danville, Pa., and colleagues.
They reported their findings in Diabetes Care and in the Diabetes Care symposium at the American Diabetes Association meeting.
”Patients in remission experienced the biggest changes in FGF19 and bile acids,” Argyropoulos said. ”We hypothesize that bile acids play a major role in FGF19, which … may sensitize patients to insulin.”
RYGB surgery leads to remission of diabetes in a large proportion of patients, but the mechanism behind this relationship isn’t well understood. FGF19 has been associated with the regulation of hepatic bile acid production, so the researchers speculated that this pathway may play a role in that remission.
Argyropoulos and colleagues assessed data from two cohorts of bariatric surgery patients: one with 66 patients with diabetes and 54 patients without the disease; a second with 115 diabetic and 71 non-diabetic patients.
They split the cohort into three groups: RYGB patients without diabetes, RYGB with diabetes who had remission for at least 12 months after surgery, and RYGB patients with diabetes who didn’t have remission of diabetes after surgery.
Pre-operatively, patients with diabetes had lower levels of FGF19 and higher bile acid levels than non-diabetic patients, ”suggesting the possible presence of an impairment in the enterohepatic FGF19-[bile acid, (BA)] pathway in the diabetic state,” the researchers wrote.
In genetic analyses, lower levels of FGF19 correlated with higher hepatic cholesterol 7 alpha-hydroxylase (CYP7A1) — a modulator of bile acid production — in diabetic patients, but not in non-diabetic patients (P<0.048).
Overall, the researchers found that serum FGF19 levels increased for the majority of all groups of patients following bariatric surgery, but diabetic patients who went into remission had the greatest increases of all three groups (P<0.001).
Diabetic patients in remission also had the greatest increases in total bile acids, they found (P<0.001). Specifically, the greatest increases in cholic and deoxycholic acids were seen in this group, and although all groups saw increases in chenodeoxycholic acid (CDCA), gains were greatest among those in remission from diabetes (P<0.01 for all).
The researchers noted that cholic acid has been inversely related with insulin resistance, suggesting it could play a key role in remission of diabetes after bariatric surgery.
Argyropoulos said the likely mechanism could be that with surgery, bile acids get secreted into an empty duodenum and travel directly to the distal small intestine, which is closer to the ileum, where FGF19 is produced.
These bile acids may be more bioactive since they don’t come in contact with food, and may be able alter hepatic glucose oxidation and stimulate FGF19 production, he said, adding that this may re-sensitize the liver to FGF19 and promote glucose homeostasis.
Mitchell Roslin, MD, of Lenox Hill Hospital in New York City, who was not involved in the study, said the research is ”very valid” given that it’s been known that bile acids ”are an important part of the equation” in bariatric surgery.
”I don’t think it’s the bile acids or FGF19 themselves, but I think they are passengers that allow bacteria or inflammatory agents to get into a patient’s system,” Roslin said.
He added that other inflammatory diseases also appear to be mediated by bariatric surgery, including psoriasis and rheumatoid arthritis.
”They get markedly better,” he said, ”and I think the same pathway is involved.”
The study was supported by the Geisinger Clinic and the NIH.
The researchers reported no conflicts of interest.
From www.medpagetoday.com
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