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

Abstract

We hypothesized that individuals who have undergone gastric bypass have greater insulin sensitivity that obese subjects but less compared with lean. We measured free fatty acid (FFA) and glucose kinetics during a two-step, hyperinsulinemic euglycemic clamp in nondiabetic subjects who were 38 Ϯ 5 mo post-gastric bypass surgery (GB; n ϭ 15), in lean subjects (L; n ϭ 15), and in obese subjects (O; n ϭ 16). Fasting FFAa were not significantly different between the three study groups but during both doses of insulin were significantly higher in O than in either GB or L. The effective insulin concentration resulting in half-maximal suppression of FFA was similar in L and GB and significantly less in both groups compared with O. Glucose infusion rates during low-dose insulin were not significantly different in GB compared with either L or O. During high-dose insulin, glucose infusion rates were significantly greater in GB than in O but less than in L. Endogenous glucose production in GB was significantly lower than O only during low dose of insulin. We conclude that gastric bypass is associated with improvements in adipose tissue insulin sensitivity to levels similar to lean, healthy persons and also with improvements in the response of glucose metabolism to insulin. These changes may be due to preferential reduction in visceral fat and decreased FFA availability. However, some differences in insulin sensitivity in GB remain compared with L. Residual insulin resistance may be related to excess total body fat or abnormal lipolysis and requires further study. insulin sensitivity; glucose; body composition; obesity OBESITY IS FREQUENTLY ACCOMPANIED by insulin resistance (5). Elevated circulating free fatty acid (FFA) concentrations, due to increased adipose tissue lipolysis, are thought to mediate insulin resistance in both obesity and type 2 diabetes (4). Weight loss via a hypocaloric diet has been shown to reduce lipolysis in obese individuals (14). However, although gastric bypass surgery has been shown to improve insulin action on glucose metabolism, relatively little is known about the effect of gastric bypass surgery on the insulin sensitivity of adipose tissue.We measured FFA kinetics during a two-step hyperinsulinemic euglycemic clamp in nondiabetic individuals who had undergone gastric bypass surgery and in nondiabetic lean and obese subjects. We hypothesized that gastric bypass subjects have greater insulin sensitivity with respect to lipolysis compared with obese subjects but less than lean subjects. We also hypothesized that gastric bypass subjects would have greater insulin sensitivity with respect to glucose kinetics than obese subjects but less than lean subjects and that there would be a relationship between adipose tissue insulin sensitivity and the sensitivity of glucose metabolism to insulin.Research design and methods. The Mayo Institutional Review Board approved the study, and subjects gave informed consent. The Mayo Clinical Research Unit (CRU) was used for this study. Three groups of nondiabetic sub...

Mechanisms of improved glycaemic control after Roux-en-Y gastric bypass

“…Using the HEC with a glycerol tracer and indirect calorimetry, a large increase in lipolysis and lipid oxidation rates has also been shown during the first 2-3 weeks after RYGB, with normalisation at the 1 year follow-up [20]. In another study, insulin-mediated suppression of NEFA in RYGB-operated patients was comparable to that in lean controls and was significantly greater than that in obese controls more than 1 year postoperatively [74].…”

What causes the insulin resistance underlying obesity?

“…The most commonly performed bariatric procedure, Roux-en-Y gastric bypass, results in resolution of T2DM in approximately 80% of patients [44 ▪ ]. A recent study using hyperinsulinemic euglycemic clamps in humans demonstrated an improvement in adipose tissue insulin sensitivity with significant suppression of lipolysis after the Roux-en-Y gastric bypass procedure [45]. Although the mechanisms leading to the dramatic improvement in glucose homeostasis are not well understood, it appears that they involve both weight-dependent and independent processes.…”

“…This immediate effect of improvement in glucose homeostasis is not seen in other bariatric procedures that do not include a component of gastrointestinal bypass. Similarly, partial removal of the subcutaneous (liposuction) or visceral (omentectomy) adipose depots do not improve insulin sensitivity [45,46]. …”

Weight Change–Adjusted Effects of Gastric Bypass Surgery on Glucose Metabolism: 2- and 10-Year Results From the Swedish Obese Subjects (SOS) Study

“…Changes in the postprandial secretory pattern of incretins, such as glucagon-like peptide 1, are generally suggested as the major component of this effect, although alterations in dietary habits, gastric emptying, bile acids, and/or microbiota have also been put forward as possible mechanisms that could explain this phenomenon (19). Indeed, remission of type 2 diabetes has been reported within days to weeks after GBP surgery, before substantial weight reduction has occurred (20,21).…”