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


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Authors
Roberts, Geoffrey P 
Kay, Richard G 
Howard, James 
Hardwick, Richard H 
Abstract

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.

Description
Keywords
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
1550-7289
1878-7533
Volume Title
14
Publisher
Elsevier BV
Sponsorship
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)