Background & Aims Visceral adipose tissue (VAT) is an important risk factor for the metabolic complications associated with obesity. Therefore, a reduction in VAT is considered an important target of obesity therapy. Therefore, we evaluated whether reducing VAT mass by surgical removal of the omentum, improves insulin sensitivity and metabolic function in obese patients. Methods We conducted: 1) a 12-month randomized controlled trial to determine whether reduction in VAT by omentectomy in 22 obese subjects enhances Roux-en-Y gastric bypass (RYGB) surgery-induced improvement in hepatic and skeletal muscle insulin sensitivity, assessed by using the hyperinsulinemic-euglycemic clamp technique, and 2) a 3-month longitudinal single-arm study to determine whether laparoscopic omentectomy alone in 7 obese subjects with type 2 diabetes mellitus (T2DM) improves insulin sensitivity, assessed by using the Frequently Sampled Intravenous Glucose Tolerance Test. Results The greater omentum, weighing 0.82 kg (95% CI: 0.67–0.97) was removed from subjects who had omentectomy in both studies. In study 1, muscle insulin sensitivity (relative increase in glucose disposal during insulin infusion) approximately doubled and hepatic insulin sensitivity increased by ~4-fold at 12 months after RYGB alone and RYGB plus omentectomy compared with baseline (P<0.001). There were no significant differences between groups (P>0.87) or group×time interactions (P>0.36). In study 2, surgery had no effect on insulin sensitivity (P=0.844) and use of diabetes medications. Conclusions These results demonstrate that decreasing VAT through omentectomy, whether performed alone or in combination with RYGB surgery, does not improve metabolic function in obese patients.

Background In the Single Ventricle Reconstruction (SVR) trial, one-year transplant-free survival was better for the Norwood procedure with right ventricle-to-pulmonary artery shunt (RVPAS) compared with a modified Blalock-Taussig shunt (MBTS) in patients with hypoplastic left heart and related syndromes. At 6 years, we compared transplant-free survival and other outcomes between the groups. Methods Medical history was collected annually using medical record review, telephone interviews, and the death index. The cohort included 549 patients randomized and treated in the SVR trial. Results Transplant-free survival for the RVPAS vs. MBTS groups did not differ at 6 years (64% vs. 59%, P=0.25) or with all available follow-up of 7.1±1.6 years (log-rank P=0.13). The RVPAS vs. MBTS treatment effect had non-proportional hazards (P=0.009); the hazard ratio (HR) for death or transplant favored the RVPAS before Stage II surgery (HR=0.66; 95% CI 0.48–0.92). The effect of shunt type on death or transplant was not statistically significant between Stage II to Fontan surgery (HR 1.36, 95% CI 0.86–2.17, p=0.17) or after the Fontan procedure (HR 0.76, 95% CI 0.33–1.74, p=0.52). By 6 years, RVPAS patients had a higher incidence of catheter interventions (0.38 vs. 0.23/patient-year, P<0.001), primarily due to more interventions between the Stage II and Fontan procedures (HR=1.72, 95% CI 1.00–3.03). Complications did not differ by shunt type; by 6 years, one in five patients had had a thrombotic event and one in six, seizures. Conclusions By 6 years, the hazards of death or transplant and catheter interventions were not different between the RVPAS vs. MBTS groups. Children assigned to the RVPAS group had 5% higher transplant-free survival but the difference did not reach statistical significance, and they required more catheter interventions. Both treatment groups have accrued important complications. Clinical Trial Registration Registered with ClinicalTrials.gov number, NCT00115934 URL: http://clinicaltrials.gov/show/NCT00115934

Roux-en-Y gastric bypass (RYGB) surgery has become an accepted treatment for excessive obesity. We conducted a longitudinal study to assess regional body composition, muscle proteolysis, and energy expenditure before RYGB, and 6 and 12 months after RYGB. Whole-body and regional fat mass (FM) and lean mass (LM) were assessed via dual-energy X-ray absorptiometry (DXA), and myofibrillar protein degradation was estimated by urinary 3-methylhistidine (3-MeH) in 29 subjects. Energy expenditure and substrate oxidation were also determined using a whole-room, indirect calorimeter in 12 of these subjects. LM loss constituted 27.8 ± 10.2% of total weight loss achieved 12 months postoperatively, with the majority of LM loss (18 ± 6% of initial LM) occurring in the first 6 months following RYGB. During this period, the trunk region contributed 66% of whole-body LM loss. LM loss occurred in the first 6 months after RYGB despite decreased muscle protein breakdown, as indicated by a decrease in 3-MeH concentrations and muscle fractional breakdown rates. Sleep energy expenditure (SEE) decreased from 2,092 ± 342 kcal/d at baseline to 1,495 ± 190 kcal/day at 6 months after RYGB (P < 0.0001). Changes in both LM and FM had an effect on the reduction in SEE (P < 0.001 and P = 0.005, respectively). These studies suggest that loss of LM after RYGB is significant and strategies to maintain LM after surgery should be explored.

OBJECTIVE -This study tested the hypothesis that phosphodiesterase 5 inhibition alone or in combination with ACE inhibition improves glucose homeostasis and fibrinolysis in individuals with metabolic syndrome.RESEARCH DESIGN AND METHODS -Insulin sensitivity, ␤-cell function, and fibrinolytic parameters were measured in 18 adults with metabolic syndrome on 4 separate days after a randomized, crossover, double-blind, 3-week treatment with placebo, ramipril (10 mg/ day), tadalafil (10 mg o.d.), and ramipril plus tadalafil.RESULTS -Ramipril decreased systolic and diastolic blood pressure, ACE activity, and angiotensin II and increased plasma renin activity. Ramipril did not affect insulin sensitivity or ␤-cell function. In contrast, tadalafil improved ␤-cell function (P ϭ 0.01). This effect was observed in women (331.9 Ϯ 209.3 vs. 154.4 Ϯ 48.0 32 ⅐ mmol Ϫ1 ⅐ l Ϫ1 , respectively, for tadalafil treatment vs. placebo; P ϭ 0.01) but not in men. There was no effect of any treatment on fibrinolysis.CONCLUSIONS -Phosphodiesterase 5 inhibition may represent a novel strategy for improving ␤-cell function in metabolic syndrome.