ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 67 O24 | DOI: 10.1530/endoabs.67.O24

Proglucagon peptide family responses after RYGB surgery in obese patients with type 2 diabetes

Kleopatra Alexiadou1, Joyceline Cuenco1, James W Howard2, Matthieu Fleuret2, Preeshila Behary1, George Tharakan1, Nicolai J Wewer Albrechtsen3, Jens Juul Holst4, Jason Pembroke2, Robert Wheller2, Ahmed R Ahmed1, Steve R Bloom1 & Tricia M Tan1

1Section of Investigative Medicine, Imperial College London, London, UK; 2LGC Limited, Fordham, Cambridgeshire, UK; 3Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark; 4Panum Institute, Department of Biomedical Sciences and the Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark.

Objective: Bariatric surgery is currently the most effective treatment for weight loss and diabetes remission. There are conflicting reports in the literature regarding the glucagon levels after RYGB surgery, likely due to cross-reactivity with oxyntomodulin and glicentin. The aim of this study was to characterize the proglucagon peptide family responses post-RYGB surgery in obese patients with type 2 diabetes using validated assays.

Method: Nineteen obese patients with type 2 diabetes were assessed before and 1, 3 and 12 months post-RYGB surgery. All participants had anthropometric profiling as well as a mixed meal tolerance (MMT) test during each visit. Glucose, insulin, GLP-1, Oxyntomodulin, Glicentin and Glucagon levels were measured at 0,15, 30, 60, 120 and 180 minutes.

Results: Fasting and post-prandial Glucose levels and fasting Insulin levels decreased significantly whereas post-prandial GLP-1 and Oxyntomodulin levels increased significantly at 1–3 and 12 months post RYGB (P<0.0001). There was a significant decrease in fasting glucagon levels at 3 and 12 months post RYGB as well as a decrease in post-prandial levels during MMT (P<0.0001). These results were measured using an alternative Mercodia protocol and were confirmed against LC/MS-MS.

Conclusions: Fasting and post-prandial glucagon levels decrease post-RYGB in obese patients with type 2 diabetes in parallel with the improvement seen in glucose homeostasis and insulin sensitivity. Mercodia immunoassay is precise in measuring the glucagon levels minimizing the cross-reactivity with glicentin and oxyntomodulin. Analysis with LC/MS-MS corroborated these results.