Roux-en-Y gastric bypass versus calorie restriction: support for surgery per se as the direct contributor to altered responses of insulin and incretins to a mixed meal.

OBJECTIVE: To study the immediate effects of Roux-en-Y gastric bypass (RYGB) on glucose homeostasis, insulin, and incretin responses to mixed-meal tests compared with the effects of calorie restriction (CR).

SETTING: University-affiliated bariatric surgery clinic.

BACKGROUND: RYGB induces remission of type 2 diabetes (T2D) long before significant weight loss occurs. The time course and underlying mechanisms of this remission remain enigmatic. A prevailing theory is that secretory patterns of incretin hormones are altered due to rearrangement of the gastrointestinal tract. To what extent reduced calorie intake contributes to the remission of T2D is unknown.

METHODS: Nine normoglycemic patients and 10 T2D patients were subjected to mixed-meal tests (MMT) 4 weeks before surgery before initiation of a very low calorie diet regimen (MMT-4 w ), 1 day before surgery on a very low calorie diet regimen (MMT-1 d ), on the morning of the first day after surgery (MMT+1 d ; first postsurgical meal), and 6 weeks after surgery (MMT+6 w ). Insulin, glucose, active glucagon-like peptide 1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured.

RESULTS: CR lowered insulin in T2D patients, whereas glucose, GIP, and GLP-1 were unaffected. RYGB immediately increased plasma insulin and GIP. The GLP-1 response was delayed compared with the GIP response. T2D patients exhibited lower insulin responses after RYGB compared with normoglycemic patients. GIP responses were similar in both groups at all occasions, whereas T2D patients displayed markedly elevated GLP-1 responses 6 weeks after RYGB. Glucose was unaffected by CR and RYGB in both groups. Insulin sensitivity was unaffected by CR but improved with RYGB.

CONCLUSION: RYGB exerts powerful and immediate effects on insulin and incretin responses to food, independently of changes caused by CR.