Metabolic Parameters, Weight Loss, and Comorbidities 4 Years After Roux-en-Y Gastric Bypass and Sleeve Gastrectomy.

BACKGROUND: Sleeve gastrectomy (LSG) is now the predominant bariatric surgery performed, yet there is limited long-term data comparing important outcomes between LSG and Roux-en-Y gastric bypass (RYGB). This study compares weight loss and impact on comorbidities of the two procedures. METHODS: We retrospectively evaluated weight, blood pressure, hemoglobin A1c, cholesterol, and medication use for hypertension, diabetes, and hyperlipidemia at 1-4 years post-operatively in 380 patients who underwent RYGB and 334 patients who underwent LSG at the University of Michigan from January 2008 to November 2013. Follow-up rates from 714 patients initially were 657 (92%), 556 (78%), 507 (71%), and 498 (70%) at 1-4 years post-operatively. RESULTS: Baseline characteristics were similar except for higher weight and BMI in LSG. There was greater weight loss with RYGB vs. LSG at all points. Hemoglobin A1c and total cholesterol improved more in RYGB vs. LSG at 4 years. There was greater remission of hypertension and discontinuation of all medications for hypertension and diabetes with RYGB at 4 years. CONCLUSIONS: Weight loss, reduction in medications for hypertension and diabetes, improvements in markers of diabetes and hyperlipidemia, and remission rates of hypertension were superior with RYGB vs. LSG 4 years post-operatively. Choice of bariatric procedures should be tailored to surgical risk, comorbidities, and weight loss goals.

Milestone Weight Loss Goals (Weight Normalization and Remission of Obesity) after Gastric Bypass Surgery: Long-Term Results from the University of Michigan.

BACKGROUND: Rates of weight normalization and obesity remission after Roux-en-Y gastric bypass (GB) are unknown. This study evaluated weight loss, rates of achieving body mass index (BMI) <25 or 30 kg/m2, recidivism, and predictors of success following GB. METHODS: We retrospectively studied weight and BMI at baseline, 2 and 6 months, and annually at 1-7 years in 219 patients undergoing GB at the University of Michigan from January 2008 to November 2010. RESULTS: Follow-up was excellent for a population traditionally associated with high attrition rates with data availability of 157/219, 145/219, 144/219, 134/219, 123/219, 82/161, and 29/64 patients at 1-7 years, respectively. Mean baseline BMI was 47.0 kg/m2. Weight normalization (BMI <25 kg/m2) occurred in 2.3-6.8% of patients. More importantly, 47% of patients achieved remission of obesity (BMI <30 kg/m2) at some time point and 24% (52/219) at the last observed time point. BMI <30 kg/m2 was associated with a lower initial BMI and follow-up for more than 2 years. CONCLUSIONS: Rates of weight normalization are low after GB; however, a large number of patients achieved BMI <30 kg/m2. While the percent total weight loss and excess weight loss are both quite high in the entire cohort and this is likely associated with significant health benefits, our results still underscore the need to address obesity with intensive clinical attention earlier in its course.

Roux-En-Y Gastric Bypass Vs. Sleeve Gastrectomy: Balancing the Risks of Surgery with the Benefits of Weight Loss.

BACKGROUND: The purpose of the study was to compare weight loss, metabolic parameters, and postoperative complications in patients undergoing Roux-en-Y gastric bypass (GB) and sleeve gastrectomy (SG). METHODS: We retrospectively studied 30-day postoperative complications as well as change in weight, blood pressure, cholesterol, hemoglobin, hemoglobin A1C, and creatinine from baseline to 2, 6, 12, and 24 months postoperatively in 383 patients undergoing GB and 336 patients undergoing SG at the University of Michigan from January 2008 to November 2013. For a study population which typically has high attrition rates, there were excellent follow-up rates (706/719 at 2 months, 566/719 at 6 months, 519/719 at 12 months, and 382/719 at 24 months). RESULTS: Baseline characteristics were similar in both groups except for higher weight and BMI in the SG group. The GB group experienced greater total body weight loss at 6, 12, and 24 months (41.9 vs. 34.6 kg at 24 months, p < 0.0001). Excess weight loss was 69.7 and 51.7 % following GB and SG respectively at 24 months (p < 0.0001). BP improved significantly in both groups. Surgical complication rates were greater after GB (10.1 vs. 3.5 %, p = 0.0007) with no significant difference in life-threatening or potentially life-threatening complications. CONCLUSIONS: Weight loss was greater following GB compared to SG at 2 years. The risk for surgical complications was greater following GB. Surgical intervention should be tailored to surgical risk, comorbidities, and desired weight loss.

Alterations in lipid signaling underlie lipodystrophy secondary to AGPAT2 mutations.

Congenital generalized lipodystrophy (CGL), secondary to AGPAT2 mutation is characterized by the absence of adipocytes and development of severe insulin resistance. In the current study, we investigated the adipogenic defect associated with AGPAT2 mutations. Adipogenesis was studied in muscle-derived multipotent cells (MDMCs) isolated from vastus lateralis biopsies obtained from controls and subjects harboring AGPAT2 mutations and in 3T3-L1 preadipocytes after knockdown or overexpression of AGPAT2. We demonstrate an adipogenic defect using MDMCs from control and CGL human subjects with mutated AGPAT2. This defect was rescued in CGL MDMCs with a retrovirus expressing AGPAT2. Both CGL-derived MDMCs and 3T3-L1 cells with knockdown of AGPAT2 demonstrated an increase in cell death after induction of adipogenesis. Lack of AGPAT2 activity reduces Akt activation, and overexpression of constitutively active Akt can partially restore lipogenesis. AGPAT2 modulated the levels of phosphatidic acid, lysophosphatidic acid, phosphatidylinositol species, as well as the peroxisome proliferator-activated receptor γ (PPARγ) inhibitor cyclic phosphatidic acid. The PPARγ agonist pioglitazone partially rescued the adipogenic defect in CGL cells. We conclude that AGPAT2 regulates adipogenesis through the modulation of the lipome, altering normal activation of phosphatidylinositol 3-kinase (PI3K)/Akt and PPARγ pathways in the early stages of adipogenesis.

Role of FoxO1 in FFA-induced oxidative stress in adipocytes.

Reactive oxygen species (ROS) production has recently been established as an essential contributor in the pathogenesis of obesity-associated insulin resistance. The FoxO1 pathway plays a role not only in nutrient sensing but also in regulating ROS production. We exposed adipocytes to free fatty acids (FFA) and demonstrated that FoxO1 protein levels decrease in a dose-dependent manner. The FoxO1 downregulation correlated with an increase in the production of ROS and a proinflammatory adipokine pattern characterized by a decrease in adiponectin and an increase in IL-6, plasminogen activator inhibitor-1, and monocyte chemotactic protein-1 mRNA expression levels. Similarly, a decrease in FoxO1 protein levels was seen in adipocytes of db/db mice compared with controls. Treatment with the sirtuin agonist resveratrol, which translocates FoxO1 to the nucleus, increased FoxO1 protein levels in adipocytes exposed to FFA. This correlated with a decrease in the generation of ROS and a partial reversal of the proinflammatory adipokine pattern. Together these results indicate that the insulin-resistant adipocyte produced by the exposure to a high concentration of fatty acids is characterized by decreased levels of FoxO1. These data also suggest that modulation of the Sirt1/FoxO1 pathway is a potentially useful therapeutic target for the obesity-induced dysfunctional adipocyte.