A patient with severe obesity (BMI 45 kg/m2) has undergone Roux-en-Y gastric bypass. Six months post-surgery, she shows dramatic resolution of type 2 diabetes even before significant weight loss. The MOST likely hormonal mechanism is:

• A Increased ghrelin secretion from the bypassed gastric fundus stimulates pancreatic beta cells
• B Elevated FGF21 from the bypassed duodenum acting as an insulin sensitizer
• C Increased peptide YY from bypassed jejunum reducing hepatic glucose production
• D Markedly elevated post-meal GLP-1 secretion from L-cells of the ileum due to early nutrient delivery to the distal gut ✓

Explanation

After Roux-en-Y bypass, undigested nutrients reach the distal ileum (L-cell rich region) far more rapidly and in greater amounts than before surgery. This triggers a massive exaggerated GLP-1 (glucagon-like peptide 1) secretion post-meals. GLP-1 enhances glucose-dependent insulin secretion, suppresses glucagon, delays gastric emptying, and promotes satiety — collectively resolving T2DM before caloric restriction-induced weight loss occurs (the 'hindgut hypothesis'). Ghrelin is actually reduced post-bypass from the excluded fundus, not increased.

Reference: Harper's Illustrated Biochemistry, 32nd ed.

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Written and medically reviewed by the StethoPrep medical team.