1. Mechanisms of remission in type 2 diabetes mellitus using Roux-en-Y gastric bypass
- Author
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Carswell, Kirstin, Amiel, Stephanie Anne, and Patel, Ameet
- Abstract
Introduction: Defects in fat processing, in particular non-esterified fatty acids (NEFA), may hold the link between obesity, hyperlipidaemia, insulin resistance (IR) and type 2 diabetes mellitus (T2DM). The secretion of insulin, more effective at inhibiting lipolysis than glucose production, is inhibited by high NEFA levels. I hypothesised that postprandial hormone alterations following Roux-en-Y gastric bypass (RYGB) improve adipocyte insulin sensitivity through the peripheral effects of incretins. Methods: Participants with T2DM (n=9) and without T2DM [NDM] (n=10) underwent RYGB for morbid obesity. Fasting and postprandial blood was analysed for glycaemic, lipidaemic and gut hormones changes around surgery. Intra-operatively, adipose tissue biopsies were taken and lipolysis assessed during a 2hr incubation with pre- and post-RYGB plasma and relevant hormonal concentrations. Results: By post-operative day 4, there were improvements in IR (p<0.0001) and reduced fasting insulin levels (p=0.0017) despite no reduction in postprandial insulin (p=0.6714). Fasting NEFA levels were reduced in NDM (p<0.05) but not in the T2DM group (p=0.0816), whilst postprandial NEFA (∆AUC [360min]) reduced in the T2DM group (p<0.0001) but not in the NDM group (p=0.4111), ANOVA p<0.05. Significant changes in gut hormone levels around RYGB were noted, in fasting: reduced GIP (p=0.0079), PYY (p=0.0066) and ghrelin levels (p=0.0005); post-prandial: increased GLP-1 (p=0.0018) and PYY levels (p<0.0001); reduced GIP (p=0.0318) and ghrelin levels (p=0.0004). Incubation of adipocytes in both fasting and postprandial plasma post-RYGB resulted in increased lipolysis versus pre-RYGB plasma (peripheral p=0.0235 and p=0.0205, respectively [n=8]). Insulin and PYY inhibited lipolysis but no effect of GLP-1, GIP and ghrelin on lipolysis was detected. Conclusions: Although likely that postprandial hormonal alterations improve adipocyte lipolysis through their peripheral effects, it is most likely the global reduction in insulin levels, thereby reducing the anti-lipolytic effect, combined with overall improvements in IR, responsible for these findings and not the peripheral effects of incretins.
- Published
- 2017