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T2DM resolution

Proteins central to T2DM resolution following RYGB

Greater decrease of both Fetuin-A and RBP4 seen after bypass than after sleeve

Roux-en-y gastric bypass results in a greater early decrease in several proteins and several metabolites compared with laparoscopic sleeve gastrectomy (LSG), which could explain why bypass patients present with enhanced resolution of type 2 diabetes according to a study published in PlosOne.

The outcomes seem to support the foregut hypothesis that nutrient bypass of the upper gut leads to reduction in secretion of an unidentified gut peptide which promotes insulin resistance.

The researchers from the University of Auckland, North Shore Hospital, Middlemore Hospital, Auckland City Hospital, Auckland, New Zealand, the University of Hong Kong, and the University of New South Wales, Sydney, Australia, sought to identify the insulin resistance-associated proteins and metabolites, which decrease more after bypass than after sleeve gastrectomy (LSG) prior to diabetes remission.

They carried out a non-randomised, matched, prospective controlled intervention trial that compared the acute effect of bypass to sleeve, compared with matched caloric intake, on glycaemia among  21 obese patients with type 2 diabetes.

Eight patients had a bypass and seven a sleeve. Approximately three days prior to surgery and three days post-surgery blood samples were collected for analysis.


The researchers identified six proteins that were significantly lower and four significantly higher after both surgery types, four proteins increased and one decreased after sleeve, while only one protein increased after bypass. Two proteins, retinol binding protein 4 (RBP4) and Fetuin-A have been previously reported in the context of insulin resistance and significantly decreased: RBP4 decreased to 72% after bypass, p<0.01, and Fetuin-A decreased to 75% after bypass, p<0.05 (Figure 1).


Figure 1: Proteomic results for Fetuin-A and RBP4

“The greater decrease of both Fetuin-A and RBP4 seen after GBP than after SG is consistent with an impact of foregut exclusion on reducing these proteins…Further studies are required to document the functional evolution of gut microbiota after foregut excluding GBP compared to restrictive types of bariatric surgery such as SG in order to test these hypotheses” the authors write.

“Our proteomic analysis showed a significant decrease in two proteins involved in insulin resistance, RBP4 and Fetuin-A, three days after GBP but not SG,” they conclude. “Notably, although insulin resistance had not improved significantly three days after bariatric surgery, the statistically significant correlations between the levels of RBP4 and Fetuin-A with HOMA-IR support a direct relationship between lower levels of these proteins and improved insulin resistance in our dataset.”

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