RESUMO
BACKGROUND: Venous thromboembolism (VTE) is a leading cause of 30-day mortality after metabolic and bariatric surgery (MBS). Multiple predictive tools exist for VTE risk assessment and extended VTE chemoprophylaxis determination. OBJECTIVE: To review existing risk-stratification tools and compare their predictive abilities. SETTING: MBSAQIP database. METHODS: Retrospective analysis of the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) database was performed (2015-2019) for primary minimally invasive MBS cases. VTE clinical factors and risk-assessment tools were evaluated: body mass index threshold of 50 kg/m2, Caprini risk-assessment model, and 3 bariatric-specific tools: the Cleveland Clinic VTE risk tool, the Michigan Bariatric Surgery Collaborative tool, and BariClot. MBS patients were deemed high risk based on criteria from each tool and further assessed for sensitivity, specificity, and positive predictive value. RESULTS: Overall, 709,304 patients were identified with a .37% VTE rate. Bariatric-specific tools included multiple predictors: procedure, age, race, gender, operative time, length of stay, heart failure, and dyspnea at rest; operative time was the only variable common to all. The body mass index cutoff and Caprini risk-assessment model had higher sensitivity but lower specificity when compared with the Michigan Bariatric Surgery Collaborative and BariClot tools. While the sensitivity of the tools varied widely and was overall low, the Cleveland Clinic tool had the highest sensitivity. The bariatric-specific tools would have recommended extended prophylaxis for 1.1%-15.6% of patients. CONCLUSIONS: Existing MBS VTE risk-assessment tools differ widely for inclusion variables, high-risk definition, and predictive performance. Further research and registry inclusion of all significant risk factors are needed to determine the optimal risk-stratified approach for predicting VTE events and determining the need for extended prophylaxis.
Assuntos
Cirurgia Bariátrica , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controle , Melhoria de Qualidade , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Anticoagulantes/uso terapêutico , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/métodos , Fatores de RiscoRESUMO
BACKGROUND: The National Comprehensive Cancer Network guidelines recommend harvesting 16 or more lymph nodes for the adequate staging of gastric adenocarcinoma. This study examines the rate of adequate lymphadenectomy over recent years, its predictors, and its impact on overall survival(OS). STUDY DESIGN: The National Cancer Database was utilized to identify patients who underwent surgical treatment for gastric adenocarcinoma between 2006-2019. Trend analysis was performed for lymphadenectomy rates during the study period. Logistic regression, Kaplan-Meier survival plots, and Cox proportional hazard regression were utilized. RESULTS: A total of 57,039 patients who underwent surgical treatment for gastric adenocarcinoma were identified. Only 50.5% of the patients underwent a lymphadenectomy of ≥ 16 nodes. Trend analysis showed that this rate significantly improved over the years, from 35.1% in 2006 to 63.3% in 2019 (p < .0001). The main independent predictors of adequate lymphadenectomy included high-volume facility with ≥ 31 gastrectomies/year (OR: 2.71; 95%CI:2.46-2.99), surgery between 2015-2019 (OR: 1.68; 95%CI: 1.60-1.75), and preoperative chemotherapy (OR:1.49; 95%CI:1.41-1.58). Patients with adequate lymphadenectomy had better OS than patients who did not: median survival: 59 versus 43 months (Log-Rank: p < .0001). Adequate lymphadenectomy was independently associated with improved OS (HR:0.79; 95%CI:0.77-0.81). Laparoscopic and robotic gastrectomies were independently associated with adequate lymphadenectomy compared to open, OR: 1.11, 95%CI:1.05-1.18 and OR: 1.24, 95%CI:1.13-1.35, respectively. CONCLUSION: Although the rate of adequate lymphadenectomy improved over the study period, a large number of patients still lacked adequate lymph node dissection, negatively impacting their OS despite multimodality therapy. Laparoscopic and robotic surgeries were associated with a significantly higher rate of lymphadenectomy ≥ 16 nodes.
Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Prognóstico , Excisão de Linfonodo , Linfonodos/cirurgia , Linfonodos/patologia , Gastrectomia , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
BACKGROUND: Enhanced recovery protocols (ERPs) after metabolic and bariatric surgery (MBS) may help decrease length of stay (LOS) and postoperative nausea/vomiting but implementation is often fraught with challenges. The primary aim of this pilot study was to standardize a MBS ERP with a real-time data support dashboard and checklist and assess impact on global and individual element compliance. The secondary aim was to evaluate 30 day outcomes including LOS, hospital readmissions, and re-operations. METHODS AND PROCEDURES: An ERP, paper checklist, and virtual dashboard aligned on MBS patient care elements for pre-, intra-, and post-operative phases of care were developed and sequentially deployed. The dashboard includes surgical volumes, operative times, ERP compliance, and 30 day outcomes over a rolling 18 month period. Overall and individual element ERP compliance and outcomes were compared pre- and post-implementation via two-tailed Student's t-tests. RESULTS: Overall, 471 patients were identified (pre-implementation: 193; post-implementation: 278). Baseline monthly average compliance rates for all patient care elements were 1.7%, 3.7%, and 6.2% for pre-, intra-, and post-operative phases, respectively. Following ERP integration with dashboard and checklist, the intra-operative phase achieved the highest overall monthly average compliance at 31.3% (P < 0.01). Following the intervention, pre-operative acetaminophen administration had the highest monthly mean compliance at ≥ 99.1%. Overall TAP block use increased 3.2-fold from a baseline mean rate of 25.4-80.8% post-implementation (P < 0.01). A significant decrease in average intra-operative monthly morphine milligram equivalents use was noted with a 56% drop pre- vs. post-implementation. Average LOS decreased from 2.0 to 1.7 days post-implementation with no impact on post-operative outcomes. CONCLUSION: Implementation of a checklist and dashboard facilitated ERP integration and adoption of process measures with many improvements in compliance but no impact on 30 day outcomes. Further research is required to understand how clinical support tools can impact ERP adoption among MBS patients.
Assuntos
Cirurgia Bariátrica , Recuperação Pós-Cirúrgica Melhorada , Humanos , Projetos Piloto , Assistência Perioperatória/métodos , Tempo de Internação , Estudos RetrospectivosRESUMO
OBJECTIVES: To measure changes in the composition of serum bile acids (BA) and the expression of Takeda G-protein-coupled receptor 5 (TGR5) acutely after bariatric surgery or caloric restriction. SUMMARY BACKGROUND DATA: Metabolic improvement after bariatric surgery occurs before substantial weight loss. BA are important metabolic regulators acting through the farnesoid X receptor and TGR5 receptor. The acute effects of surgery on BA and the TGR5 receptor in subcutaneous white adipose tissue (WAT) are unknown. METHODS: A total of 27 obese patients with type 2 diabetes mellitus were randomized to Roux-en-Y gastric bypass (RYGB) or to hypocaloric diet (HC diet) restriction (NCT 1882036). A cohort of obese patients with and without type 2 diabetes mellitus undergoing vertical sleeve gastrectomy was also recruited (n = 12) as a comparison. RESULTS: After vertical sleeve gastrectomy, the level of BA increased [total: 1.17â±â1.56âµmol/L to 4.42â±â3.92âµmol/L (P = 0.005); conjugated BA levels increased from 0.99â±â1.42âµmol/L to 3.59â±â3.70âµmol/L (P = 0.01) and unconjugated BA levels increased from 0.18â±â0.24âµmol/L to 0.83â±â0.70âµmol/L (P = 0.009)]. With RYGB, there was a trend toward increased BA [total: 1.37â±â0.97âµmol/L to 3.26â±â3.01âµmol/L (P = 0.07); conjugated: 1.06â±â0.81âµmol/L to 2.99â±â3.02âµmol/L (P = 0.06)]. After HC diet, the level of unconjugated BA decreased [0.92â±â0.55âµmol/L to 0.32 ± 0.43âµmol/L (P = 0.05)]. The level of WAT TGR5 gene expression decreased after surgery, but not in HC diet. Protein levels did not change. CONCLUSIONS: The levels of serum BA increase after bariatric surgery independently from caloric restriction, whereas the level of WAT TGR5 protein is unaffected.
Assuntos
Cirurgia Bariátrica , Ácidos e Sais Biliares/sangue , Diabetes Mellitus Tipo 2/cirurgia , Dieta Redutora , Obesidade/cirurgia , Receptores Acoplados a Proteínas G/sangue , Adulto , Feminino , Humanos , Immunoblotting , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: Mitochondrial dysfunction in adipose tissue has been implicated as a pathogenic step in the development of type 2 diabetes mellitus (T2DM). In adipose tissue, chronic nutrient overload results in mitochondria driven increased reactive oxygen species (ROS) leading to carbonylation of proteins that impair mitochondrial function and downregulation of key genes linked to mitochondrial biogenesis. In patients with T2DM, Roux-en-Y gastric bypass (RYGB) surgery leads to improvements in glycemic profile prior to significant weight loss. Consequently, we hypothesized that improved glycemia early after RYGB would be paralleled by decreased protein carbonylation and increased expression of genes related to mitochondrial biogenesis in adipose tissue. METHODS: To evaluate this hypothesis, 16 obese individuals were studied before and 7-8 days following RYGB and adjustable gastric banding (AGB). Subcutaneous adipose tissue was obtained pre- and post-bariatric surgery as well as from eight healthy, non-obese individual controls. RESULTS: Prior to surgery, adipose tissue expression of PGC1α, NRF1, Cyt C, and eNOS (but not Tfam) showed significantly lower expression in the obese bariatric surgery group when compared to lean controls (p < 0.05). Following RYGB, but not after AGB, patients showed significant decrease in HOMA-IR, reduction in adipose protein carbonylation, and increased expression of genes linked to mitochondrial biogenesis. CONCLUSIONS: These results suggest that rapid reduction in protein carbonylation and increased mitochondrial biogenesis may explain postoperative metabolic improvements following RYGB.
Assuntos
Derivação Gástrica , Biogênese de Organelas , Carbonilação Proteica , Gordura Subcutânea/metabolismo , Adulto , Estudos de Casos e Controles , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Óxido Nítrico Sintase/genética , Óxido Nítrico Sintase/metabolismo , Fator 1 Nuclear Respiratório/genética , Fator 1 Nuclear Respiratório/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , RNA Mensageiro/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: Despite providing superb excess weight loss and increased resolution of comorbid diseases, such as type 2 diabetes mellitus, compared to other bariatric procedures, the duodenal switch/ biliopancreatic diversion (DS/BD) has not gained widespread acceptance among patients and physicians. In this study, we investigated outcomes, symptoms and complications among postsurgical DS patients compared to RYGB patients. METHODS: We used propensity scores to retrospectively match patients who underwent DS/BD between 2005 and 2010 to comparable Roux-en-Y gastric bypass (RYGB) patients. We then reviewed patient charts, and surveyed patients using the University of Minnesota Bariatric Surgery Outcomes Survey tool to track outcomes, comorbid illnesses and complications. RESULTS: One hundred ninety consecutive patients underwent primary DS/BD between 2005 and 2010 at the University of Minnesota Medical Center. There were 178 patients available for follow-up (93.7%) who were matched to 139 RYGB patients. Type 2 diabetes, hypertension, and hyperlipidemia all significantly improved in each group. Improvements were significantly higher in the DS/BD group. Percent total weight loss was not different between groups. Loose stools and bloating symptoms were more frequently reported among DS/BD patients. With the exception of increased emergency department visits among DS/BD patients (P < .01), overall complication rates were not significantly different between DS/BD and RYGB. There was no difference in mortality rates between the groups. CONCLUSION: The DS/BD is a robust procedure that engenders both superior weight loss and improvement of major comorbidities. Complication and adverse event rates are similar to those of RYGB.
Assuntos
Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/métodos , Desvio Biliopancreático/efeitos adversos , Derivação Gástrica/efeitos adversos , Obesidade Mórbida/cirurgia , Adulto , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Hiperlipidemias/complicações , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/complicações , Obesidade Mórbida/patologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Resultado do Tratamento , Redução de PesoRESUMO
BACKGROUND AND OBJECTIVES: Complications resulting in hospital readmission are important concerns for those considering bariatric surgery, yet present understanding of the risk for these events is limited to a small number of patient factors. We sought to identify demographic characteristics, concomitant morbidities, and perioperative factors associated with hospital readmission following bariatric surgery. METHODS: We report on a prospective observational study of 24,662 patients undergoing primary RYGB and 26,002 patients undergoing primary AGB at 249 and 317 Bariatric Surgery Centers of Excellence (BSCOE), respectively, in the United States from January 2007 to August 2009. Data were collected using standardized assessments of demographic factors and comorbidities, as well as longitudinal records of hospital readmissions, complications, and mortality. RESULTS: The readmission rate was 5.8% for RYGB and 1.2% for AGB patients 30 days after discharge. The greatest predictors for readmission following RYGB were prolonged length of stay (adjusted odds ratio [OR], 2.3; 95% confidence interval [CI], 2.0-2.7), open surgery (OR, 1.8; CI, 1.4-2.2), and pseudotumor cerebri (OR, 1.6; CI, 1.1-2.4). Prolonged length of stay (OR, 2.3; CI, 1.6-3.3), history of deep venous thrombosis or pulmonary embolism (OR, 2.1; CI, 1.3-3.3), asthma (OR, 1.5; CI, 1.1-2.1), and obstructive sleep apnea (OR, 1.5; CI, 1.1-1.9) were associated with the greatest increases in readmission risk for AGB. The 30-day mortality rate was 0.14% for RYGB and 0.02% for AGB. CONCLUSION: Readmission rates are low and mortality is very rare following bariatric surgery, but risk for both is significantly higher after RYGB. Predictors of readmission were disparate for the two procedures. Results do not support excluding patients with certain comorbidities since any reductions in overall readmission rates would be very small on the absolute risk scale. Future research should evaluate the efficacy of post-surgical managed care plans for patients at higher risk for readmission and adverse events.
Assuntos
Cirurgia Bariátrica/efeitos adversos , Readmissão do Paciente/estatística & dados numéricos , Adulto , Cirurgia Bariátrica/mortalidade , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , RiscoRESUMO
BACKGROUND: There are myriad symptoms and signs of gastrojejunal leak; prompt recognition is essential. Many surgeons use clinical predictors to guide selective use of upper gastrointestinal imaging (UGI). The appropriate practice remains undefined. STUDY DESIGN: A review of patients who underwent primary laparoscopic Roux-en-Y gastric bypass between January 2002 and December 2008 was conducted. All underwent routine UGI studies on postoperative day 1. Actual gastrojejunal leak within 7 days of surgery (actual leak [AL], radiologic leaks), operative reports, patient charts, and postoperative vital signs were retrospectively reviewed. RESULTS: There were 2,099 operations. Eight ALs (0.43%) occurred without associated mortality. UGI was positive in 7 AL patients and falsely positive in 6 patients. The AL patients underwent laparoscopy on postoperative days 1 and 3 (n = 5 and n = 1, respectively), laparotomy on postoperative day 3 (n = 1), and peritoneal drainage (n = 1). False-positive UGIs prompted laparoscopy (n = 3) and close observation (n = 3). Pulse was 100 to 120 beats per minute in 2 patients and fever (>38.5°C) was present in 0 AL patients. AL patients had osteogenesis imperfecta (n = 1), macronodular cirrhosis (n = 1), positive bubble test (n = 3), and concomitant splenectomy (n = 1). No jejunojejunostomy leaks were identified. CONCLUSIONS: Routine UGI after laparoscopic Roux-en-Y gastric bypass has greater sensitivity than clinical signs for detecting gastrojejunal leak. Delay in the diagnosis of leakage can impact mortality, and this suggests that indications for routine UGI might still exist. Tachycardia is not a reliable early marker of leak. There might be risk factors for leak in addition to vital signs, including patient medical history or intraoperative events, which should prompt routine UGI on postoperative day 1.
Assuntos
Fístula Anastomótica/diagnóstico por imagem , Fístula Anastomótica/diagnóstico , Derivação Gástrica , Feminino , Derivação Gástrica/métodos , Trato Gastrointestinal/diagnóstico por imagem , Humanos , Laparoscopia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Radiografia , Estudos Retrospectivos , Fatores de Risco , Grampeamento CirúrgicoRESUMO
OBJECTIVE: To compare the relative efficacy of medical management, the duodenal switch (DS), and the laparoscopic adjustable gastric band (LAGB) to the Roux-en-Y gastric bypass (RYGB) for treatment of type 2 diabetes mellitus (T2DM). BACKGROUND: The RYGB resolves T2DM in a high proportion of patients and is considered the standard operation for T2DM resolution in morbidly obese patients. However, no data exist comparing the efficacy of medical management and other bariatric operations to the RYGB for treatment of T2DM in comparable patient populations. METHODS: We performed a retrospective case-matched study of morbidly obese patients with T2DM who had undergone medical management (nonsurgical controls [NSC]; N = 29), LAGB (N = 30), or DS (N = 27) and were compared with matched T2DM patients who had undergone RYGB. Matching was performed with respect to age, sex, body mass index, and hemoglobin A1C (HbA1C). Outcomes assessed were changes in body mass index, HbA1C, and diabetes medication scores at 1 year. RESULTS: The Roux-en-Y gastric bypass produced greater weight loss, HbA1C normalization, and medication score reduction compared to both NSC and LAGB-matched cohorts. Duodenal switch produced greater reductions in HbA1C and medication score than RYGB, despite no greater weight loss at 1 year. Surgical complications were rarely life threatening. CONCLUSIONS: This study provides an important perspective about the comparative efficacy of LAGB, DS, and NSC to the RYGB for treatment of T2DM among obese patients. After 1 year of follow-up, RYGB is superior to NSC and LAGB with respect to weight loss and improvement in diabetes whereas DS is superior to RYGB in reducing HbA1C and medication score.
Assuntos
Cirurgia Bariátrica/métodos , Diabetes Mellitus Tipo 2/cirurgia , Hipoglicemiantes/uso terapêutico , Obesidade Mórbida/complicações , Índice de Massa Corporal , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Derivação Gástrica , Gastroplastia , Hemoglobinas Glicadas/metabolismo , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Redução de PesoRESUMO
BACKGROUND: The treatment goals recommended by the American Diabetes Association (ADA) for patients with type 2 diabetes mellitus include hemoglobin A1c (HbA1C) <7.0%, low-density lipoprotein (LDL) <100 mg/dL, and systolic blood pressure (SBP) <130 mmHg. Only 10% of conventionally treated patients reach these goals as a composite endpoint. The efficacy of the Roux-en-Y gastric bypass (RYGB) in meeting this composite endpoint has not been reported. METHODS: We compared our database of patients with type 2 diabetes undergoing RYGB to a database of patients with medically managed type 2 diabetes and at least 2 years of follow-up data. RESULTS: Ultimately, 152 RYGB patients were compared to 115 routine medical management (RMM) patients for whom data on the composite endpoint were available over 2 years. The results show significant decrease in body mass index (kilograms per square meter) in the RYGB group compared to the RMM group (P < 0.001). HbA1C, LDL cholesterol, and SBP all significantly improved in the RYGB group (all P ≤ 0.01) and did not demonstrate any significant change in the RMM group. Over 2 years, when evaluating all three endpoints, the RYGB group (10.5% to 38.2%, P < 0.001) demonstrated increased achievement of the ADA goals compared to the RMM group (13.9% to 17.4%, P = 0.47). There was a significant decrease in medication use in the RYGB cohort; however, discontinuation of medications was sometimes inappropriate. CONCLUSIONS: RYGB achieves the ADA composite endpoint more frequently than conventional therapy and with less medication.
Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/cirurgia , Derivação Gástrica , Obesidade Mórbida/epidemiologia , Obesidade Mórbida/cirurgia , Adolescente , Adulto , Idoso , Pressão Sanguínea , Índice de Massa Corporal , LDL-Colesterol/sangue , Estudos de Coortes , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Seguimentos , Derivação Gástrica/estatística & dados numéricos , Hemoglobinas Glicadas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/fisiopatologia , Probabilidade , Resultado do Tratamento , Estados Unidos/epidemiologia , Redução de Peso , Adulto JovemRESUMO
BACKGROUND: Outcomes of bariatric surgery in patients with a body mass index (BMI) <35 kg/m(2) have been an active area of investigation. We examined the comparative effectiveness of Roux-en-Y gastric bypass (RYGB) to routine medical management (nonsurgical controls; NSCs) in achieving appropriate targets defined by the American Diabetes Association for type 2 diabetes mellitus (T2DM) in patients with class I obesity (BMI 30.0-34.9 kg/m(2)) T2DM at 1 year. METHODS: We identified patients undergoing RYGB (N = 17) with both class I obesity and T2DM and compared them to similar NSC (N = 17) treated in the Primary Care Center. Data were collected at baseline and 1 year for systolic blood pressure (SBP), as well as blood levels for low-density lipoprotein (LDL) cholesterol and hemoglobin A1c (HbA1c). RESULTS: After RYGB, BMI decreased from 34.6 ± 0.8 kg/m(2) to 25.8 ± 2.5 kg/m(2) (P < .001) and HbA1c decreased from 8.2 ± 2.0% to 6.1 ± 2.7% (P < .001). The NSC cohort had no significant change in either BMI or HbA1c. SBP and LDL did not significantly change in either group. The RYGB group had a decrease in medication use compared to the NSC group (P < .001). The RYGB group ceased the use of antihypertensive and antihyperlipidemia medications by 1 year despite abnormal values. CONCLUSION: RYGB can be performed in patients with both a BMI <35 kg/m(2) and T2DM with better weight loss, glycemic control, and fewer antihyperglycemic medications than NSC. Inappropriate cessation of medications may partially explain the persistent increase in both SBP and LDL after RYGB.
Assuntos
Complicações do Diabetes/cirurgia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Derivação Gástrica , Obesidade/complicações , Obesidade/cirurgia , Idoso , Anti-Hipertensivos/uso terapêutico , Glicemia/metabolismo , Pressão Sanguínea , Índice de Massa Corporal , LDL-Colesterol/sangue , Complicações do Diabetes/patologia , Complicações do Diabetes/fisiopatologia , Complicações do Diabetes/terapia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Derivação Gástrica/efeitos adversos , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Obesidade/patologia , Obesidade/terapia , Estudos Retrospectivos , Redução de PesoRESUMO
Insulin resistance is associated with obesity but mechanisms controlling this relationship in humans are not fully understood. Studies in animal models suggest a linkage between adipose reactive oxygen species (ROS) and insulin resistance. ROS oxidize cellular lipids to produce a variety of lipid hydroperoxides that in turn generate reactive lipid aldehydes that covalently modify cellular proteins in a process termed carbonylation. Mammalian cells defend against reactive lipid aldehydes and protein carbonylation by glutathionylation using glutathione-S-transferase A4 (GSTA4) or carbonyl reduction/oxidation via reductases and/or dehydrogenases. Insulin resistance in mice is linked to ROS production and increased level of protein carbonylation, mitochondrial dysfunction, decreased insulin-stimulated glucose transport, and altered adipokine secretion. To assess protein carbonylation and insulin resistance in humans, eight healthy participants underwent subcutaneous fat biopsy from the periumbilical region for protein analysis and frequently sampled intravenous glucose tolerance testing to measure insulin sensitivity. Soluble proteins from adipose tissue were analyzed using two-dimensional gel electrophoresis and the major carbonylated proteins identified as the adipocyte and epithelial fatty acid-binding proteins. The level of protein carbonylation was directly correlated with adiposity and serum free fatty acids (FFAs). These results suggest that in human obesity oxidative stress is linked to protein carbonylation and such events may contribute to the development of insulin resistance.