Hepatic and peripheral insulin sensitivity and diabetes remission at 1 month after Roux-en-Y gastric bypass surgery in patients randomized to omentectomy

OBJECTIVE

Early after Roux-en-Y gastric bypass (RYGB), there is improvement in type 2 diabetes, which is characterized by insulin resistance. We determined the acute effects of RYGB, with and without omentectomy, on hepatic and peripheral insulin sensitivity. We also investigated whether preoperative diabetes or postoperative diabetes remission influenced tissue-specific insulin sensitivity after RYGB.

RESEARCH DESIGN AND METHODS

We studied 40 obese (BMI 48 ± 8 kg/m²) participants, 17 with diabetes. Participants were randomized to RYGB alone or in conjunction with omentectomy. Hyperinsulinemic-euglycemic clamps with isotopic-tracer infusion were completed at baseline and at 1 month postoperatively to assess insulin sensitivity.

RESULTS

Participants lost 11 ± 4% of body weight at 1 month after RYGB, without an improvement in peripheral insulin sensitivity; these outcomes were not affected by omentectomy, preoperative diabetes, or remission of diabetes. Hepatic glucose production (HGP) and the hepatic insulin sensitivity index improved in all subjects, irrespective of omentectomy (P ≤ 0.001). Participants with diabetes had higher baseline HGP values (P = 0.003) that improved to a greater extent after RYGB (P = 0.006). Of the 17 participants with diabetes, 10 (59%) had remission at 1 month. Diabetes remission had a group × time effect (P = 0.041) on HGP; those with diabetes remission had lower preoperative and postoperative HGP.

CONCLUSIONS

Peripheral insulin sensitivity did not improve 1 month after RYGB, irrespective of omentectomy, diabetes, or diabetes remission. Hepatic insulin sensitivity improved at 1 month after RYGB and was more pronounced in patients with diabetes. Improvement in HGP may influence diabetes remission early after RYGB.Of the estimated 26 million people in the U.S. with type 2 diabetes and the 79 million with prediabetes (1), ～80% are overweight or obese. Roux-en-Y gastric bypass (RYGB) surgery for treatment of obesity leads to long-term diabetes remission in ～80% of patients (2), whereas very limited effects are observed with lifestyle intervention (3). Improvements in diabetes are reported to occur immediately after RYGB (4), with ～30% of patients being discharged from the hospital with discontinuation of all diabetes medications (5).Impaired insulin sensitivity (insulin resistance) at the liver and in the periphery (primarily skeletal muscle) is an underlying mechanism of and precursor to diabetes (6). Several studies have described a long-term improvement in peripheral and hepatic insulin sensitivity 6 months to 1 year after RYGB (7–9), which is considered to occur secondary to weight loss. The mechanisms of the immediate improvement in diabetes after RYGB, before substantial weight loss, are not well delineated. Improvements in insulin sensitivity are reported early after RYGB, by hyperglycemic clamp at 1 and 4 weeks postoperatively (10) or by intravenous glucose tolerance tests (11) and homeostasis model assessment (HOMA) during the first week postoperatively (11,12). These approaches to measure insulin sensitivity, however, cannot distinguish between peripheral and hepatic insulin sensitivity. The hyperinsulinemic-euglycemic clamp method in conjunction with isotopically labeled tracer infusion allows measurement of peripheral (primarily skeletal muscle) insulin sensitivity as well as hepatic glucose production (HGP) and hepatic insulin sensitivity. Two studies have used this technique to assess insulin sensitivity early after RYGB, and interestingly, did not find a significant improvement in peripheral insulin sensitivity 2 to 4 weeks after RYGB; however, hepatic insulin sensitivity was not assessed (13,14). Recently, Camastra et al. (7) reported that peripheral and hepatic insulin sensitivity did not change at 2 weeks after RYGB in patients with and without diabetes.Increased visceral fat is considered an important risk factor for diabetes and insulin resistance (15). We recently reported, however, that surgical removal of the greater omentum (omentectomy) in conjunction with RYGB did not augment the improvement in insulin sensitivity long-term after RYGB (8). Here we report the acute effects of RYGB with or without omentectomy on hepatic and skeletal muscle insulin sensitivity. This was assessed by hyperinsulinemic-euglycemic clamp with tracer infusion at 1 month after RYGB. We also tested the hypothesis that an early remission of diabetes after RYGB is associated with improved hepatic and peripheral insulin sensitivity.