Beta-cell sensitivity to glucose is impaired after gastric bypass surgery.

AIMS: Patients with Roux-en-Y gastric bypass surgery (GB) have exaggerated postprandial insulin secretion, which has been attributed to increased meal glucose appearance and enhanced incretin effect. Here we sought to determine β-cell glucose sensitivity in the absence of meal stimulation and insulinotropic gut factors. MATERIALS AND METHODS: Twelve non-diabetic subjects with prior GB, and 7 matched non-surgical controls with normal glucose tolerance were studied. Blood glucose and insulin secretion rates were measured during a graded glucose infusion at increasing and then decreasing rates. Insulin sensitivity (SI ) and glucose effectiveness (SG ) were determined by the minimal model. RESULTS: The GB subjects had comparable SI to the controls. The GB subjects had relative hyperglycemia during highest dose of glucose infusion associated with significantly reduced β-cell glucose sensitivity throughout both step-up (GB: 34±6, CN: 82±9 pmol.min-1 .mM-1 .L, p<0.0001) and step-down (GB: 31±6, CN: 74±9 pmol.min-1 .mM-1 .L, p<0.0001) phases of the glucose infusion. The GB subjects also had reduced SG (GB: 0.04±0.00, CN: 0.07±0.01 min-1 , p = 0.004). CONCLUSION: In the absence of enteric stimuli β-cell sensitivity to changes in glycemia is blunted among individuals with GB, indicating a significant shift in a fundamental property of β-cell function several years after surgery.