Lower Fetuin-A, Retinol Binding Protein 4 and Several Metabolites after Gastric Bypass Compared to Sleeve Gastrectomy in Patients with Type 2 Diabetes

Abstract

BackgroundBypass of foregut secreted factors promoting insulin resistance is hypothesized to be one of the mechanisms by which resolution of type 2 diabetes (T2D) follows roux-en-y gastric bypass (GBP) surgery.AimTo identify insulin resistance-associated proteins and metabolites which decrease more after GBP than after sleeve gastrectomy (SG) prior to diabetes remission.MethodsFasting plasma from 15 subjects with T2D undergoing GBP or SG was analyzed by proteomic and metabolomic methods 3 days before and 3 days after surgery. Subjects were matched for age, BMI, metformin therapy and glycemic control. Insulin resistance was calculated using homeostasis model assessment (HOMA-IR). For proteomics, samples were depleted of abundant plasma proteins, digested with trypsin and labeled with iTRAQ isobaric tags prior to liquid chromatography-tandem mass spectrometry analysis. Metabolomic analysis was performed using gas chromatography-mass spectrometry. The effect of the respective bariatric surgery on identified proteins and metabolites was evaluated using two-way analysis of variance and appropriate post-hoc tests.ResultsHOMA-IR improved, albeit not significantly, in both groups after surgery. Proteomic analysis yielded seven proteins which decreased significantly after GBP only, including Fetuin-A and Retinol binding protein 4, both previously linked to insulin resistance. Significant decrease in Fetuin-A and Retinol binding protein 4 after GBP was confirmed using ELISA and immunoassay. Metabolomic analysis identified significant decrease of citrate, proline, histidine and decanoic acid specifically after GBP.ConclusionGreater early decrease was seen for Fetuin-A, Retinol binding protein 4, and several metabolites after GBP compared to SG, preceding significant weight loss. This may contribute to enhanced T2D remission observed following foregut bypass procedures.

Medium-Term Results of Laparoscopic Sleeve Gastrectomy: a Matched Comparison with Gastric Bypass

“…The reason for these findings is that duodenal exclusion might have a significant role in the treatment diabetes apart from weight reduction. A recent study comparing LSG and RYGB identified some duodenal factors that are possibly related to duodenal exclusion supported the duodenal exclusion theory [30]. In this study, the patients who received gastric bypass had significant lower HbA1c and LDL levels than did those who received LSG at 5 years after surgery.…”

Bariatric surgery and nonalcoholic fatty liver disease

“…The effect of bariatric surgery on the circulating levels of fetuin-A remains to be fully elucidated. A fall in levels has been reported in the immediate postoperative period [139] and up to 16 months after surgery [146]. However, one study reported a rise in serum fetuin-A levels in patients with NASH 4 weeks postoperatively [145], which returned to preoperative levels at 6 months.…”

“…Retinal-binding protein 4 (RBP4) and fetuin-A are two further insulin-blunting mediators that have been shown to be reduced following bariatric procedures [138][139][140]. RBP4 is a vitamin A transport protein secreted by adipocytes and hepatocytes that has been shown to induce insulin resistance in muscle, liver and fat [141].…”

“…Postoperative reductions in RPB4 levels have been reported inconsistently [140] and seem to be related to weight loss rather than to weight-independent mechanisms, with similar reductions seen in patients achieving significant dietary weight loss [139]. Interestingly, bypass procedures are associated with a greater reduction in RBP4 levels compared with sleeve gastrectomy, with authors proposing reduced duodenal absorption of retinol as causing downregulation of RBP receptor expression [139].…”

Analysis of the plasma proteome using iTRAQ and TMT‐based Isobaric labeling

“…In research related to T2D, Jullig et al used iTRAQ labeling of plasma to identify factors that favor resolution of T2D in subjects undergoing roux‐en‐y gastric bypass (GBP) surgery when compared with sleeve gastrectomy ( n = 15) . Culnan and co‐workers also considered changes in the plasma proteome associated with gastric by‐pass surgery .…”