Improvement in β-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 ␤-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 ␤-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 ϭ 16) and hyperglycemia (n ϭ 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 (Ϫ54% at 1 mo, P Ͻ 0.005) and increased DI (23-fold at 6 mo vs. baseline, P Ͻ 0.05). Over 24 mo, DI improved in subjects with hyperglycemia (15-fold vs. baseline, P Ͻ 0.005) and also modestly in subjects with normoglycemia (58%, P Ͻ 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, ␤-cell function improved early following RYGB, due largely to increases in insulin secretion. For both normoglycemic and hyperglycemic subjects, further improvement or stabilization of ␤-cell function over the 2 yr is due largely to improved Si associated with reduced adiposity. disposition index; weight loss; adipose tissue mass SEVERE OBESITY, DEFINED AS body mass index greater than 40 kg/m 2 , is associated with an increased prevalence of type 2 diabetes (T2DM) (5). Bariatric surgery is the most efficient method of producing substantial weight loss in severely obese patients (42). Surgical procedures induce weight loss by reducing the volume of the stomach, thereby restricting food intake, or by diverting the flow of ingested food to the ileum and bypassing the duodenum and the proximal jejunum, which promotes malabsoption (39). Roux-en-Y gastric bypass (RYGB) is a common and restrictive plus malabsorptive procedure; other procedures include adjustable gastric banding, a restrictive-only surgery, and biliopancreatic diversion, a primarily malabsorptive procedure that is less common in the US. (39).As has been found in overweight and obese individuals (47), severely obese persons with prediabetes and diabetes have a decline in ␤-cell function such that insulin secretion is inadequate to compensate for reduced insulin sensitivity (Si) (19,37). A special feature of bariatric surgery is its ability to induce remission of T2DM (9). Following adjustable gastric banding, remission of diabetes is strongly related to weight loss (15, 38). However, a greater effect of diabetes resolution is seen with malabsor...

Immediate enhancement of first-phase insulin secretion and unchanged glucose effectiveness in patients with type 2 diabetes after Roux-en-Y gastric bypass

“…However, in the longer-term, weight loss will improve insulin sensitivity in adipose tissue and decrease circulating free fatty acids, which may have additional beneficial effects on insulin secretion (4,14). In line with previous findings, we did not observe improved intrinsic ␤-cell function in normoglycemic individuals, whose ␤-cells by definition are not exposed to a glucotoxic environment, further supporting the proposed role of glucotoxicity (18,36,41,43,48,52). First-phase insulin secretion increased nonsignificantly in the IGT group.…”

“…A novel finding of the present study is the demonstration of an early enhancement of first-phase insulin secretion to iv glucose within 1 wk after surgery in patients with type 2 diabetes, before any major weight loss. Previous studies using IVGTTs have reported gradually increased first-phase insulin secretion in patients with type 2 diabetes in the first year after RYGB, attributed to weight loss (10,18,25,36,41,43,48,52). One study performed an IVGTT within the first week after RYGB and did not report significantly improved AIRg in patients with type 2 diabetes (48).…”

Early Enhancements of Hepatic and Later of Peripheral Insulin Sensitivity Combined With Increased Postprandial Insulin Secretion Contribute to Improved Glycemic Control After Roux-en-Y Gastric Bypass

“…In addition, relief of gluco-and lipotoxicity has been proposed as potential contributors to improved b-cell function based previous reports of gradual improvement in insulin secretion in response to an IV glucose bolus (12,14,(22)(23)(24). However, in our study, patients with T2D displayed unchanged insulin secretion in response to the IV challenge despite reductions in fasting glucose concentrations and FA levels (at 1 year).…”

“…In contrast, after intravenous (IV) challenges, insulin secretion increases more gradually after RYGB in patients with T2D (14,(22)(23)(24) and even declines in glucosetolerant subjects (24,25). Improved b-cell function after RYGB thus may be linked to the oral rather than the IV route of administration (6).…”

Gastric bypass surgery is associated with near-normal insulin suppression of lipolysis in nondiabetic individuals

“…Adjusting palmitate R a for differences in insulin concentrations produced similar results, particularly at HDI, where insulin concentrations were similar in lean and post-gastric bypass subjects. The improvement of insulin sensitivity after gastric bypass in terms of peripheral glucose disposal has been studied using a number of well-established techniques, including calculated indices of insulin sensitivity such as homeostasis of model assessment (3), intravenous (16) and oral glucose tolerance tests (24), and glucose clamps (as we used in our study) (1,3). However, there is only one report showing that lipolysis is reduced after gastric bypass surgery.…”