Improvement in ß-cell function in patients with normal and hyperglycemia following Roux-en-Y gastric bypass surgery

Abstract

Glycemic disorders resolve following Roux-en-Y gastric bypass (RYGB) surgery, but early and longer-term mechanisms regarding effects on β-cell dysfunction as well as relationships with decreasing adiposity are not well understood. We evaluated longitudinal changes in peripheral insulin sensitivity (Si), the acute insulin response to glucose (AIRg), and the composite estimate of β-cell function, the disposition index (DI), over 24 mo via frequently sampled intravenous glucose tolerance testing in severely obese women who had fasting normoglycemia (n = 16) and hyperglycemia (n = 11) before RYGB surgery; homeostatic model assessment (HOMA-IR) estimated insulin resistance; air displacement plethysmography determined adipose tissue mass. At baseline, subjects with normoglycemia had adequate DI associated with elevated AIRg, but DI was markedly reduced in subjects with hyperglycemia. Within 1-6 mo post-RYGB, glycemic control was normalized in subjects with hyperglycemia related to reduced HOMA-IR (-54% at 1 mo, P < 0.005) and increased DI (23-fold at 6 mo vs. baseline, P < 0.05). Over 24 mo, DI improved in subjects with hyperglycemia (15-fold vs. baseline, P < 0.005) and also modestly in subjects with normoglycemia (58%, P < 0.05), due largely to increased Si. Decreasing adiposity correlated with longer-term HOMA-IR and Si values at 6 and 24 mo, respectively. In patients exhibiting fasting hyperglycemia before surgery, β-cell function improved early following RYGB, due largely to increases in insulin secretion. For both normoglycemic and hyperglycemic subjects, further improvement or stabilization of β-cell function over the 2 yr is due largely to improved Si associated with reduced adiposity.

Figures

Fig. 1.

Baseline insulin action and responses following Roux-en-Y gastric bypass (RYGB) surgery in patients with normoglycemia and hyperglycemia. The impact of RYGB on peripheral insulin sensitivity (Si, μU·min−1·ml−1, ○ and dotted line), the acute insulin response to glucose (AIRg, μU·ml−1·min−1, ▵ and dashed line) and the disposition index (DI, min−1, ■ and solid line) were measured via intravenous glucose tolerance test from baseline to 24 mo in severely obese women (n = 15) with normoglycemia and hyperglycemia at baseline, as described in materials and methods.

Fig. 2.

Graphic representation of the relationship between Si and insulin secretion during the 24-mo intervention period. Relationships are depicted between Si and AIRg in severely obese women with normoglycemia (■) and hyperglycemia at baseline (○) from baseline to 6 and to 24 mo (depicted by arrows) following RYGB (n = 15). Data of the same relationship in healthy controls was provided by Kahn et al (24); the mean relationship as well as the 5th and 95th percentiles are presented. Hyperglycemic subjects experienced normalization of the relationship, as shown by upward and rightward shifts of their dots at 6 mo following surgery. Normoglycemic subjects were in the normal range of response of the DI at baseline and at 6 mo but experienced improvement, signified by a rightward shift of their dot, at 24 mo following surgery.