Gastrectomy with Roux-en-Y reconstruction as a lean model of bariatric surgery.

Change log
Roberts, Geoffrey P 
Kay, Richard G 
Howard, James 
Hardwick, Richard H 

BACKGROUND: Altered enteroendocrine hormone responses are widely believed to underlie the beneficial effects of bariatric surgery in type 2 diabetes. While elevated postprandial glucagon-like peptide-1 (GLP-1) is considered one of the mediators, increased postprandial glucagon levels have recently been implicated. OBJECTIVES: We investigated hormonal responses in lean patients after prophylactic total gastrectomy (PTG), as a model of Roux-en-Y gastric bypass without the confounding effects of obesity or massive weight loss. SETTING: University hospital, United Kingdom. METHODS: Ten participants after PTG and 9 healthy volunteers were recruited for oral glucose tolerance tests. Plasma glucose, insulin, GLP-1, peptide YY, glucose-dependent insulinotropic-polypeptide, glucagon, oxyntomodulin, glucagon(1-61), and glicentin levels were assessed using immunoassays and/or mass spectrometry. RESULTS: PTG participants exhibited accelerated plasma glucose appearance, followed, in 3 of 10 cases, by hypoglycemia (<3 mM glucose). Plasma GLP-1, peptide YY, glucose-dependent insulinotropic-polypeptide, glicentin, and oxyntomodulin responses were elevated, and glucagon appeared to rise in PTG participants when measured with a glucagon-specific enzyme-linked immunosorbent assay. We revisited the specificity of this assay, and demonstrated significant cross-reactivity with glicentin and oxyntomodulin at concentrations observed in PTG plasma. Reassessment of glucagon with the same assay using a modified protocol, and by liquid chromatography-mass spectrometry, demonstrated suppression of glucagon secretion after oral glucose tolerance tests in both PTG and control cohorts. CONCLUSIONS: Care should be taken when assessing glucagon levels in the presence of elevated plasma levels of other proglucagon products. Substantial elevation of GLP-1 and insulin responses after PTG likely contribute to the observed hypoglycemia, and mirror similar hormone levels and complications observed in bariatric weight loss patients.

Bariatric surgery, Roux-en-Y gastric bypass, gastrectomy, glucagon, glucagon-like peptide-1 (GLP-1), hypoglycemia, Adult, Bariatric Surgery, Blood Glucose, Case-Control Studies, Female, Gastrectomy, Gastric Bypass, Gastric Inhibitory Polypeptide, Glucagon, Glucagon-Like Peptide 1, Glucose Tolerance Test, Humans, Hypoglycemia, Insulin, Male, Peptide YY, Proglucagon, Thinness
Journal Title
Surg Obes Relat Dis
Conference Name
Journal ISSN
Volume Title
Elsevier BV
Wellcome Trust (100574/Z/12/Z)
Medical Research Council (MC_UU_12012/3)
Medical Research Council (MC_UU_12012/5)
Wellcome Trust (106262/Z/14/Z)
MRC (MR/M0090401/1)
Evelyn Trust (unknown)
European Foundation for the Study of Diabetes (EFSD) (unknown)
Royal College of Surgeons of England (unknown)
Medical Research Council (MR/M009041/1)
Medical Research Council (MR/M024873/1)
MRC (MC_UU_00014/3)
MRC (MC_UU_00014/5)