Reduction of 8-iso-prostaglandin F2α in the first week after Roux-en-Y gastric bypass surgery.

Obesity is associated with increased markers of oxidative stress. We examined whether oxidative stress is reduced within the first week after Roux-en-Y gastric bypass (RYGB) surgery and could be related to changes in adipose tissue depots. The reactive oxygen species (ROS) marker 8-iso-prostaglandin F2α (8-iso-PGF2α) and activity of antioxidant glutathione peroxidases (GPX) in plasma were compared before and ~1 week after RYGB. The effects of RYGB on subcutaneous adipose tissue and interstitial fluid 8-iso-PGF2α levels and subcutaneous adipose tissue expression of GPX-3 were also assessed. Levels of 8-iso-PGF2α in subcutaneous and visceral adipose tissue were determined. Plasma 8-iso-PGF2α levels decreased (122 ± 75 to 56 ± 15 pg/ml, P = 0.001) and GPX activity increased (84 ± 18 to 108 ± 25 nmol/min/ml, P = 0.003) in the first week post-RYGB. RYGB also resulted in reductions of 8-iso-PGF2α in subcutaneous adipose tissue (1,742 ± 931 to 1,132 ± 420 pg/g fat, P = 0.046) and interstitial fluid (348 ± 118 to 221 ± 83 pg/ml, P = 0.046) that were comparable to plasma (26-33%, P = 0.74). Adipose GPX-3 expression was increased (6.7 ± 4.7-fold, P = 0.004) in the first postoperative week. The improvements in oxidative stress occurred with minimal weight loss (2.4 ± 3.4%, P = 0.031) and elevations in plasma interleukin-6 (18.0 ± 46.8 to 28.0 ± 58.9 pg/ml, P = 0.004). Subcutaneous and visceral adipose tissues express comparable 8-iso-PGF2α levels (1,204 ± 470 and 1,331 ± 264 pg/g fat, respectively; P = 0.34). These data suggest that RYGB affects adipose tissue leading to the restoration of adipose redox balance within the first postoperative week and that plasma 8-iso-PGF2α is primarily derived from subcutaneous adipose tissue.

Role of the foregut in the early improvement in glucose tolerance and insulin sensitivity following Roux-en-Y gastric bypass surgery.

Bypass of the foregut following Roux-en-Y gastric bypass (RYGB) surgery results in altered nutrient absorption, which is proposed to underlie the improvement in glucose tolerance and insulin sensitivity. We conducted a prospective crossover study in which a mixed meal was delivered orally before RYGB (gastric) and both orally (jejunal) and by gastrostomy tube (gastric) postoperatively (1 and 6 wk) in nine subjects. Glucose, insulin, and incretin responses were measured, and whole-body insulin sensitivity was estimated with the insulin sensitivity index composite. RYGB resulted in an improved glucose, insulin, and glucagon-like peptide-1 (GLP-1) area under the curve (AUC) in the first 6 wk postoperatively (all P ≤ 0.018); there was no effect of delivery route (all P ≥ 0.632) or route × time interaction (all P ≥ 0.084). The glucose-dependent insulinotropic polypeptide (GIP) AUC was unchanged after RYGB (P = 0.819); however, GIP levels peaked earlier after RYGB with jejunal delivery. The ratio of insulin AUC to GLP-1 and GIP AUC decreased after surgery (P =.001 and 0.061, respectively) without an effect of delivery route over time (both P ≥ 0.646). Insulin sensitivity improved post-RYGB (P = 0.001) with no difference between the gastric and jejunal delivery of the mixed meal over time (P = 0.819). These data suggest that exclusion of nutrients from the foregut with RYGB does not improve glucose tolerance or insulin sensitivity. However, changes in the foregut response post-RYGB due to lack of nutrient exposure cannot be excluded. Our findings suggest that foregut bypass may alter the incretin response by enhanced nutrient delivery to the hindgut.

The importance of caloric restriction in the early improvements in insulin sensitivity after Roux-en-Y gastric bypass surgery.

OBJECTIVE: Many of the metabolic benefits of Roux-en-Y gastric bypass (RYGB) occur before weight loss. In this study we investigated the influence of caloric restriction on the improvements in the metabolic responses that occur within the 1st week after RYGB. RESEARCH METHODS AND DESIGN: A mixed meal was administered to nine subjects before and after RYGB (average 4 +/- 0.5 days) and to nine matched, obese subjects before and after 4 days of the post-RYGB diet. RESULTS: Weight loss in both groups was minimal; the RYGB subjects lost 1.4 +/- 5.3 kg (P = 0.46) vs. 2.2 +/- 1.0 kg (P = 0.004) in the calorically restricted group. Insulin resistance (homeostasis model assessment of insulin resistance) improved with both RYGB (5.0 +/- 3.1 to 3.3 +/- 2.1; P = 0.03) and caloric restriction (4.8 +/- 4.1 to 3.6 +/- 4.1; P = 0.004). The insulin response to a mixed meal was blunted in both the RYGB and caloric restriction groups (113 +/- 67 to 65 +/- 33 and 85 +/- 59 to 65 +/- 56 nmol x l(-1) x min(-1), respectively; P < 0.05) without a change in the glucose response. Glucagon-like peptide 1 levels increased (9.2 +/- 8.6 to 12.2 +/- 5.5 pg x l(-1) x min(-1); P = 0.04) and peaked higher (45.2 +/- 37.3 to 84.8 +/- 33.0 pg/ml; P = 0.01) in response to a mixed meal after RYGB, but incretin responses were not altered after caloric restriction. CONCLUSIONS: These data suggest that an improvement in insulin resistance in the 1st week after RYGB is primarily due to caloric restriction, and the enhanced incretin response after RYGB does not improve postprandial glucose homeostasis during this time.

Roux-en-Y gastric bypass reverses renal glomerular but not tubular abnormalities in excessively obese diabetics.

BACKGROUND: Obesity and type 2 diabetes are associated with renal dysfunction, which improves after Roux-en-Y gastric bypass (RYGB). During a 12-month follow-up period, we studied prospectively the changes in glomerular and tubular functions that occurred in excessively obese diabetic and non diabetic subjects after RYGB. METHODS: The cohort included 35 patients, 54% of whom had type 2 diabetes. Glomerular filtration rate (GFR) was estimated using creatinine clearance. Tubular function was studied by measuring the ratio of urinary cystatin C to urinary creatinine (UCC ratio). RESULTS: Baseline renal parameters, anthropometric characteristics, and changes in body mass index after the surgical procedures were similar between the 2 cohorts. At 12 months after RYGB, creatinine clearance decreased 15% in diabetics (P = .02) and 21% in nondiabetics (P = .03). A change in GFR was seen earlier in the nondiabetics (-29% after 6 months; P = .003). The UCC ratio was increased at both 6- and 12-month follow-ups (P = .03 and .003, respectively) only in the diabetic group. CONCLUSION: GFR was improved at 12 months after RYGB, with nondiabetics showing a greater propensity score. Tubular function remained unchanged in the nondiabetic subjects, but worsening occurred in the diabetic subjects. These results underscore the importance of reversal of excessive obesity before the onset of frank diabetes.

Endocrine and metabolic response to gastric bypass.

PURPOSE OF REVIEW: Diabetes resolves in 80% of individuals undergoing successful Roux-en-Y gastric bypass. Absolute caloric restriction alone resulting from gastric anatomic changes indeed leads to weight loss; however, immediate effects in glycemic control often precede substantial weight loss typically associated with insulin sensitivity. One putative explanation relates to hormonal effects accompanying Roux-en-Y gastric bypass. We reviewed the existing and recent literature to investigate the hormonal changes accompanying Roux-en-Y gastric bypass. RECENT FINDINGS: Changes in levels of five candidate enteric hormones have been recently associated with early postoperative glycemic control following Roux-en-Y gastric bypass; the strongest effects are seen with variations in glucagon-like peptide-1, glucose-dependent insulinotropic peptide and ghrelin. SUMMARY: The unique hybridization of static anatomic restriction and dynamic absorptive bypass lends a duality to the beneficial effects of Roux-en-Y gastric bypass. This duality likely explains the short-term and long-term resolution of diabetes in patients undergoing Roux-en-Y gastric bypass.

Reconstruction of complex facial defects after radical resection of advanced skin cancers.

Management of patients with extensive facial skin cancers is a challenge. We present a series of nine patients with extensive facial skin cancers and our experience with managing these patients.