ABSTRACT

CONTEXT: Insulin resistance (IR) is a risk factor for type 2 diabetes, diabetic kidney disease, cardiovascular disease and non-alcoholic steatohepatitis. Biliopancreatic diversion (BPD) is the most effective form of bariatric surgery for improving insulin sensitivity.

OBJECTIVE: To identify plasma proteins correlating with the early restoration of insulin sensitivity after BPD.

DESIGN: Prospective single centre study including twenty insulin resistant men with morbid obesity scheduled for BPD. Patient characteristics and blood samples were repeatedly collected from baseline up to four weeks post-surgery. IR was assessed by HOMA-IR, Matsuda Index and by studying metabolic profiles during meal tolerance tests. Unbiased proteomic analysis was performed to identify plasma proteins altered by BPD. Detailed plasma profiles were made on a selected set of proteins by targeted multiple reaction monitoring mass spectrometry (MRM/MS). Changes in plasma proteome were evaluated in relation to metabolic and inflammatory changes.

RESULTS: BPD resulted in improved insulin sensitivity and reduced body weight. Proteomic analysis identified 29 proteins changed following BPD. Changes in plasma levels of afamin, apolipoprotein A-IV (ApoA4) and apolipoprotein A-II (ApoA2) correlated significantly with changes in IR.

CONCLUSION: Circulating levels of afamin, ApoA4 and ApoA2 were associated with and may contribute to the rapid improvement in insulin sensitivity after BPD.