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Background: Response to metabolic surgery is heterogeneous and the metabolic states that underpin weight loss and metabolic improvement are still unclear. In this study, we investigate parameters of post-bariatric fasting glucoregulation and leverage artificial intelligence-assisted whole-slide image analyses to characterize associated immunohistologic features of the pancreas., Materials and Methods: We performed either loop duodeno-jejunostomy (DJOS) with exclusion of 1/3 of total intestinal length, loop duodeno-ileostomy with exclusion of 2/3 of total intestinal length (DiOS), or a sham operation on 8-week-old male obese ZDF rats. Six months post-operative, we measured blood metabolites and hormones. Subsequently, pancreatic and intestinal tissue was removed, formalin fixed, and paraffin embedded. Immunohistologic (IHC) analyses included proliferating cell nuclear antigen (PCNA) to visualize the proliferation fraction and pancreatic and duodenal homeobox 1 (PDX 1) as a measure of pancreatic cell differentiation. For IHC quantification, all slides were digitalized and analyzed using QuPath. All analyzed slides were reviewed by two independent pathologists for correctness., Results: DJOS and DiOS were associated with preserved fasting insulin production compared to sham. Histopathologic evaluation showed significantly higher numbers of beta cells and specifically of clustered cell organization in DJOS and DiOS compared to sham. Cell proliferation (PCNA) was significantly elevated in DJOS and DiOS compared to sham., Conclusion: In this interventional model of bariatric surgery in severe genetic diabetes, we demonstrate post-operative histologic and immunohistologic features of the pancreas associated with improved fasting glucose homeostasis., (© 2022. The Author(s).) more...

Introduction: There is an ongoing debate on which procedure provides the best treatment for type 2 diabetes. Furthermore, the pathomechanisms of diabetes improvement of partly anatomically differing operations is not fully understood., Methods: A loop duodenojejunostomy (DJOS) with exclusion of one third of intestinal length, a sleeve gastrectomy (SG), or a combination of DJOS + SG was performed in 8-week-old male ZDF rats. One, three, and six months after surgery, an oral glucose tolerance test and measurements of GLP-1, GIP, insulin, and bile acids were conducted., Results: After an initial (4 weeks) equal glucose control, DJOS and DJOS + SG showed significantly lower glucose levels than SG 3 and 6 months after surgery. There was sharp decline of insulin levels in SG animals over time, whereas insulin levels in DJOS and DJOS + SG were preserved. GIP levels were significantly larger in both groups containing a sleeve at all three time points, whereas GLP-1 was equal in all groups at all time. Bile acid levels were significantly higher in the DJOS compared to the SG group at all time points. Interestingly, the additional SG in the DJOS + SG group led to lower bile acid levels 1 and 6 months postoperatively., Conclusion: The effect of SG on glucose control was transient, whereas a duodenal exclusion was the more effective procedure in this model due to a sustained pancreatic function with a preserved insulin secretion. more...

Introduction: Metabolic surgery is known to impact glucose tolerance but the exact mechanism is still unclear. Based on recently-published data, especially the role of the hindgut may require redefinition., Methods: Either a loop duodeno-jejunostomy (DJOS) with exclusion of one third of total intestinal length, a loop duodeno-ileostomy (DiOS, exclusion of two thirds), or SHAM operation was performed in 9-week-old Zucker diabetic fatty rats. One, 3, and 6 months after surgery, an oral glucose tolerance test (OGTT) and glucose-stimulated hormone analyses were conducted. Body weight was documented weekly., Results: DJOS and DiOS animals showed significantly better glucose control in all OGTTs than the SHAM group (two-way ANOVA p < 0.0001). Body weight developed largely parallel in both intervention groups; SHAM animals had gained significantly less weight after 6 months (Mann-Whitney DJOS/DiOS vs. SHAM p < 0.05, DJOS vs. DiOS p > 0.05). Operative interventions had no impact on GLP-1 and GIP levels at any time point (Mann-Whitney p > 0.05 for all). DJOS/DiOS operations could preserve insulin production up to 6 months, while there was already a sharp decline of insulin levels in the SHAM group (Mann-Whitney: DJOS/DiOS vs. SHAM p < 0.05 for all time points). Additionally, insulin sensitivity was improved significantly 1 month postoperative in both intervention groups compared to SHAM (Mann-Whitney DJOS/DiOS vs. SHAM p < 0.05)., Conclusion: The data of the current study demonstrate a sharp amelioration of glucose control after duodenal exclusion with unchanged levels of GLP-1 and GIP. Direct or delayed hindgut stimulation had no impact on glucose control in our model. more...