Purity of islet preparations and 5-year metabolic outcome of allogenic islet transplantation.

In allogenic islet transplantation (IT), high purity of islet preparations and low contamination by nonislet cells are generally favored. The aim of the present study was to analyze the relation between the purity of transplanted preparations and graft function during 5 years post-IT. Twenty-four patients with type 1 diabetes, followed for 5 years after IT, were enrolled. Metabolic parameters and daily insulin requirements were compared between patients who received islet preparations with a mean purity <50% (LOW purity) or ≥50% (HIGH purity). We also analyzed blood levels of carbohydrate antigen 19-9 (CA 19-9)-a biomarker of pancreatic ductal cells-and glucagon, before and after IT. At 5 years, mean hemoglobin A1c (HbA1c levels) (P = .01) and daily insulin requirements (P = .03) were lower in the LOW purity group. Insulin independence was more frequent in the LOW purity group (P < .05). CA19-9 and glucagon levels increased post-IT (P < .0001) and were inversely correlated with the degree of purity. Overall, our results suggest that nonislet cells have a beneficial effect on long-term islet graft function, possibly through ductal-to-endocrine cell differentiation. ClinicalTrial.gov NCT00446264 and NCT01123187.

Influence of Roux-en-Y gastric bypass on plasma bile acid profiles: a comparative study between rats, pigs and humans.

BACKGROUND: Roux-en-Y gastric bypass (RYGBP) is the most widely used bariatric surgery procedure, which induces profound metabolic and physiological effects, such as substantial improvements in obesity, type 2 diabetes and their comorbidities. Increasing evidence identifies bile acids (BAs) as signaling molecules that contribute to the metabolic improvement after RYGBP. However, how and to what extent BAs mediate the metabolic effects of RYGBP still remains unclear and requires mechanism of action studies using preclinical models. In this study, we compared plasma BA profiles before and after RYGBP in two animal models, rats and pigs, with humans to evaluate their translational potential. METHODS: Plasma BAs were profiled in rats, pigs and humans by liquid chromatography coupled with tandem mass spectrometry before and after RYGBP. RESULTS: RYGBP increased baseline plasma total BA concentrations in humans and in the two animal models to a similar extent (∼3-fold increase), despite differences in presurgery BA levels and profiles between the models. However, qualitatively, RYGBP differently affected individual plasma BA species, with similar increases in some free species (cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA)), different increases in glyco-conjugated species depending on the model and globally no increase in tauro-conjugated species whatever the model. CONCLUSIONS: The tested animal models share similar quantitative RYGBP-induced increases in peripheral blood BAs as humans, which render them useful for mechanistic studies. However, they also present qualitative differences in BA profiles, which may result in different signaling responses. Such differences need to be taken into account when translating results to humans.