Differential effects of bile acids on the postprandial secretion of gut hormones: a randomized crossover study.

Bile acids (BA) regulate postprandial metabolism directly and indirectly by affecting the secretion of gut hormones like glucagon-like peptide-1 (GLP-1). The postprandial effects of BA on the secretion of other metabolically active hormones are not well understood. The objective of this study was to investigate the effects of oral ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on postprandial secretion of GLP-1, oxyntomodulin (OXM), peptide YY (PYY), glucose-dependent insulinotropic peptide (GIP), glucagon, and ghrelin. Twelve healthy volunteers underwent a mixed meal test 60 min after ingestion of UDCA (12-16 mg/kg), CDCA (13-16 mg/kg), or no BA in a randomized crossover study. Glucose, insulin, GLP-1, OXM, PYY, GIP, glucagon, ghrelin, and fibroblast growth factor 19 were measured prior to BA administration at -60 and 0 min (just prior to mixed meal) and 15, 30, 60, 120, 180, and 240 min after the meal. UDCA and CDCA provoked differential gut hormone responses; UDCA did not have any significant effects, but CDCA provoked significant increases in GLP-1 and OXM and a profound reduction in GIP. CDCA increased fasting GLP-1 and OXM secretion in parallel with an increase in insulin. On the other hand, CDCA reduced postprandial secretion of GIP, with an associated reduction in postprandial insulin secretion. Exogenous CDCA can exert multiple salutary effects on the secretion of gut hormones; if these effects are confirmed in obesity and type 2 diabetes, CDCA may be a potential therapy for these conditions.NEW & NOTEWORTHY Oral CDCA and UDCA have different effects on gut and pancreatic hormone secretion. A single dose of CDCA increased fasting secretion of the hormones GLP-1 and OXM with an accompanying increase in insulin secretion. CDCA also reduced postprandial GIP secretion, which was associated with reduced insulin. In contrast, UDCA did not change gut hormone secretion fasting or postprandially. Oral CDCA could be beneficial to patients with obesity and diabetes.

Who will benefit from bariatric surgery for diabetes? A protocol for an observational cohort study.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) and obesity are pandemic diseases that lead to a great deal of morbidity and mortality. The most effective treatment for obesity and T2DM is bariatric or metabolic surgery; it can lead to long-term diabetes remission with 4 in 10 of those undergoing surgery having normal blood glucose on no medication 1 year postoperatively. However, surgery carries risks and, additionally, due to resource limitations, there is a restricted number of patients who can access this treatment. Moreover, not all those who undertake surgery respond equally well metabolically. The objective of the current research is to prospectively investigate predictors of T2DM response following metabolic surgery, including those directly involved in its aetiopathogenesis such as fat distribution and genetic variants. This will inform development of a clinically applicable model to help prioritise this therapy to those predicted to have remission. METHODS AND ANALYSIS: A prospective multicentre observational cohort study of adult patients with T2DM and obesity undergoing Roux-en-Y gastric bypass surgery. Patients will be comprehensively assessed before surgery to determine their clinical, metabolic, psychological, genetic and fat distribution profiles. A multivariate logistic regression model will be used to assess the value of the factors derived from the preoperative assessment in terms of prediction of diabetes remission. ETHICS AND DISSEMINATION: Formal ethics review was undertaken with a favourable opinion (UK HRA RES reference number 18/LO/0931). The dissemination plan is to present the results at conferences, in peer-reviewed journals as well as to lay media and to patient organisations. TRIAL REGISTRATION DETAILS: ClinicalTrials.gov, Identifier: NCT03842475.