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1.
Surg Obes Relat Dis ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38631926

RESUMO

BACKGROUND: Limited evidence exists on the patterns of medication use for hypertension, diabetes mellitus (DM), and dyslipidemia after bariatric surgery among Asian patients. OBJECTIVES: To investigate the patterns in the use of blood pressure-lowering, glucose-lowering, and lipid-lowering medications following BS in Korean patients with morbid obesity. SETTING: This study is a retrospective cohort study using the Health Insurance Review and Assignment claims database of South Korea (from 2019 to 2021). METHODS: We included patients who underwent BS between 2019 and 2020 in South Korea. We evaluated the treatment patterns of blood pressure-lowering, glucose-lowering, and lipid-lowering medications at 3-month intervals for 1-year following BS, including medication use, individual medication classes, and the number of medications prescribed. Furthermore, we estimated remission rates for each disorder based on patient characteristics by defining patients who discontinued their medications for at least 2 consecutive quarters as remission. RESULTS: A total of 3810 patients were included in this study. For 1-year following BS, a marked decrease in the number of patients using blood pressure-lowering, glucose-lowering, and lipid-lowering medications was observed. The most remarkable decrease occurred in glucose-lowering medications, which decreased by approximately -75.1% compared with that at baseline. This tendency was consistently observed when analyzing both the number of medications prescribed and the specific medication classes. Regarding remission rates, patients who were female, younger, and received the biliopancreatic diversion-duodenal switch as their BS showed a relatively higher incidence of remission than other groups. CONCLUSIONS: BS was associated with a decrease in the use of medications for hypertension, diabetes mellitus (DM), and dyslipidemia.

2.
Sensors (Basel) ; 23(18)2023 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-37765933

RESUMO

With the development of multimedia systems in wireless environments, the rising need for artificial intelligence is to design a system that can properly communicate with humans with a comprehensive understanding of various types of information in a human-like manner. Therefore, this paper addresses an audio-visual scene-aware dialog system that can communicate with users about audio-visual scenes. It is essential to understand not only visual and textual information but also audio information in a comprehensive way. Despite the substantial progress in multimodal representation learning with language and visual modalities, there are still two caveats: ineffective use of auditory information and the lack of interpretability of the deep learning systems' reasoning. To address these issues, we propose a novel audio-visual scene-aware dialog system that utilizes a set of explicit information from each modality as a form of natural language, which can be fused into a language model in a natural way. It leverages a transformer-based decoder to generate a coherent and correct response based on multimodal knowledge in a multitask learning setting. In addition, we also address the way of interpreting the model with a response-driven temporal moment localization method to verify how the system generates the response. The system itself provides the user with the evidence referred to in the system response process as a form of the timestamp of the scene. We show the superiority of the proposed model in all quantitative and qualitative measurements compared to the baseline. In particular, the proposed model achieved robust performance even in environments using all three modalities, including audio. We also conducted extensive experiments to investigate the proposed model. In addition, we obtained state-of-the-art performance in the system response reasoning task.

3.
Front Endocrinol (Lausanne) ; 14: 1171675, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37564975

RESUMO

Background: Bariatric surgery (BS) has a superior effect on reducing body weight and fat in patients with morbid obesity. As a result, BS mitigates obesity-related complications such as type 2 diabetes (T2D). However, few studies have shown the mechanism underlying diabetes remission after surgery. This study aimed to investigate the differences in serum hormone and inflammatory cytokine levels related to diabetes before surgery and during 12 months of follow-up in Korean patients with obesity. Methods: The study participants were patients with morbid obesity (n=63) who underwent sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) between 2016 - 2017 at seven tertiary hospitals in Korea. The patients were followed for 1 year after surgery. Results: Sixty-three patients had significant weight loss after surgery and showed improvements in clinical parameters and hormonal and inflammatory profiles. Among them, 23 patients who were diabetic preoperatively showed different remission after surgery. The levels of inflammation-related clinical parameters changed significantly in the remission group, and serum inflammatory cytokine and hormones significantly decreased at certain points and showed an overall decreasing trend. Conclusions: Our study found postoperative changes of factors in blood samples, and the changes in hormones secreted from the three major metabolic tissue (pancreas, adipose, and gut) along with the differences in multi-origin inflammatory cytokines between remission and non-remission groups provide a path for understanding how the effect of BS in improving glucose metabolism is mediated.

4.
J Nutr ; 153(3): 691-702, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36931749

RESUMO

BACKGROUND: Adipocyte dysregulation of lipid droplet (LD) metabolism caused by altered expression of LD proteins contributes to obesity-related metabolic diseases. OBJECTIVES: We aimed to investigate whether expression levels of PLIN1, CIDEA, and CIDEC were altered in adipose tissues of women with obesity and type 2 diabetes and whether their alterations were associated with metabolic risk factors. METHODS: Normal-weight (NW; 18.5 kg/m2 < BMI ≤ 25 kg/m2; n = 43), nondiabetic obese (OB; BMI > 30 kg/m2; n = 38), and diabetic obese (OB/DM; BMI > 30 kg/m2, fasting glucose ≥ 126 mg/dL, HbA1c ≥ 6.5%; n = 22) women were recruited. Metabolic parameters were measured, and expressions of PLIN1, CIDEA, CIDEC, and obesity-related genes were quantified in abdominal subcutaneous (SAT) and visceral adipose tissues (VAT). Effects of proinflammatory cytokines, endoplasmic reticulum (ER) stress inducers, and metabolic improvement agents on LD protein gene expressions were investigated in human adipocytes. RESULTS: PLIN1, CIDEA, and CIDEC expressions were lower in SAT and higher in VAT in OB subjects relative to NW subjects; however, they were suppressed in both fat depots in OB/DM subjects relative to OB (P < 0.05). Across the entire cohort, whereas VAT PLIN1 (r = 0.349) and CIDEC expressions (r = 0.282) were positively associated with BMI (P < 0.05), SAT PLIN1 (r = -0.390) and CIDEA expressions (r = -0.565) were inversely associated. After adjustment for BMI, some or all of the adipose LD protein gene expressions were negatively associated with fasting glucose (r = -0.259 or higher) and triglyceride levels (r = -0.284 or higher) and positively associated with UCP1 expression (r = 0.353 or higher) (P < 0.05). In adipocytes, LD protein gene expressions were 55-70% downregulated by increased proinflammatory cytokines and ER stress but 2-4-fold upregulated by the metabolic improvement agents exendin-4 and dapagliflozin (P < 0.05). CONCLUSIONS: The findings suggest that reduction of adipose LD protein expression is involved in the pathogenesis of metabolic disorders in women with obesity and type 2 diabetes and that increasing LD protein expression in adipocytes could control development of metabolic disorders.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Feminino , Adulto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Gotículas Lipídicas/metabolismo , Gotículas Lipídicas/patologia , Obesidade/metabolismo , Fatores de Risco , Citocinas/metabolismo , Glucose/metabolismo , Proteínas Associadas a Gotículas Lipídicas/metabolismo , Gordura Intra-Abdominal/metabolismo
5.
Sci Rep ; 12(1): 11853, 2022 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-35831319

RESUMO

The rates of early gastric cancer and type 2 diabetes mellitus(T2DM) are sharply increasing in Korea. Oncometabolic surgery in which metabolic surgery is conducted along with cancer surgery is a method used to treat gastric cancer and T2DM in one-stage operation. From 2011 to 2019, a total of 48 patients underwent long-limb Roux-en-Y gastrectomy (LRYG) in Inha University Hospital, and all data were reviewed retrospectively. A 75 g oral glucose tolerance test and serum insulin level test were performed before and 1 week and 1 year after surgery. One year after LRYG operation, 25 of 48 patients showed complete or partial remission and 23 patients showed non-remission of T2DM. The preoperative HbA1c level was significantly lower and the change in HbA1c was significantly greater in the T2DM remission group. Insulin secretion indices(insulinogenic index and disposition index) were increased significantly in the T2DM remission group. In contrast, the insulin resistance indices (homeostatic model assessment of insulin resistance (HOMA-IR) and Matsuda index) changed minimal. In the case of LRYG in T2DM patients, remnant ß cell function is an important predictor of favorable glycemic control.


Assuntos
Diabetes Mellitus Tipo 2 , Derivação Gástrica , Resistência à Insulina , Obesidade Mórbida , Neoplasias Gástricas , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/cirurgia , Derivação Gástrica/métodos , Hemoglobinas Glicadas/metabolismo , Humanos , Obesidade Mórbida/cirurgia , Indução de Remissão , Estudos Retrospectivos , Neoplasias Gástricas/cirurgia , Resultado do Tratamento
6.
Obesity (Silver Spring) ; 30(7): 1430-1441, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35722819

RESUMO

OBJECTIVE: Leukocyte cell-derived chemotaxin 2 (LECT2) is an obesity-upregulated hepatokine inducing skeletal muscle insulin resistance. The study's aim was to explore whether LECT2 is expressed in human adipose tissue and whether the expression is dysregulated during obesity and associated with obesity-related metabolic disorders. METHODS: This study measured metabolic parameters, serum LECT2, and expression of LECT2 and CD209, a gene encoding a putative receptor for LECT2, in abdominal subcutaneous and visceral adipose tissues in women with obesity (with or without type 2 diabetes) and women with normal weight. The expression/secretion of LECT2 and its putative effects were assessed in human adipocytes. RESULTS: Adipose tissue LECT2 mRNA and serum LECT2 were higher in women with obesity and were significantly correlated with parameters related to insulin resistance. LECT2 was mainly expressed by adipocytes. Both LECT2 and CD209 expression was higher in adipocytes from women with obesity. Incubating adipocytes with substances mimicking the microenvironment of obesity adipose tissue increased LECT2 expression/secretion. LECT2 treatment of adipocytes suppressed insulin-stimulated Akt phosphorylation; it reduced adiponectin (ADIPOQ) and increased leptin (LEP) expression in a CD209-dependent manner. CONCLUSIONS: This study demonstrates that LECT2 expression in adipose tissue is high in patients with obesity and associated with insulin resistance and suggests that adipocyte-derived LECT2 may contribute to adipose tissue dysfunction.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Tecido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Resistência à Insulina/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Obesidade/genética , Obesidade/metabolismo , República da Coreia/epidemiologia
7.
Diabetes Obes Metab ; 24(7): 1224-1234, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35257467

RESUMO

AIM: To explore how bariatric surgery (BS) modified the obesity-associated gut microbiome, the host metabolome, and their interactions in obese Korean patients. MATERIALS AND METHODS: Stool and fasting blood samples were obtained before and 1, 3, 6, and 12 months after BS from 52 patients enrolled in the Korean Obesity Surgical Treatment Study. We analysed the gut microbiome by 16S rRNA gene sequencing and the serum metabolome, including bile acids, by nuclear magnetic resonance spectroscopy and ultrahigh-performance liquid chromatography/triple quadrupole mass spectrometry. RESULTS: Stool metagenomics showed that 27 microbiota were enriched and 14 microbiota were reduced after BS, whereas the abundances and diversity of observed features were increased. The levels of branched-chain amino acids and metabolites of energy metabolism in serum were decreased after surgery, whereas the levels of metabolites related to microbial metabolism, including dimethyl sulphone, glycine, and secondary bile acids, were increased in the serum samples. In addition, we found notable mutual associations among metabolites and gut microbiome changes attributed to BS. CONCLUSIONS: Changes in the gut microbiome community and systemic levels of amino acids and sugars were directly derived from anatomical changes in the gastrointestinal tract after BS. We hypothesized that the observed increases in microbiome-related serum metabolites were a result of complex and indirect changes derived from BS. Ethnic-specific environmental or genetic factors could affect Korean-specific postmetabolic modification in obese patients who undergo BS.


Assuntos
Cirurgia Bariátrica , Microbioma Gastrointestinal , Ácidos e Sais Biliares , Microbioma Gastrointestinal/genética , Humanos , Metaboloma , Metabolômica/métodos , Metagenômica , Obesidade/cirurgia , RNA Ribossômico 16S/genética
8.
J Clin Endocrinol Metab ; 107(3): e1057-e1073, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-34718616

RESUMO

CONTEXT: The upregulation of TRIB3 (Tribbles homolog 3), a stress-inducible gene encoding a pseudokinase, has been implicated in the development of insulin resistance in the skeletal muscle and liver of patients with obesity and type 2 diabetes. However, there is little information regarding TRIB3 expression in human adipose tissue. OBJECTIVE: To investigate whether TRIB3 expression is dysregulated in human adipose tissue in the context of obesity and type 2 diabetes and whether TRIB3 expression in adipose tissues is associated with insulin resistance. METHODS: We measured metabolic parameters and TRIB3 expression in abdominal subcutaneous and visceral adipose tissue in obese (with or without type 2 diabetes) and normal-weight women. Regulation of TRIB3 expression was studied in human adipocytes. RESULTS: TRIB3 expression in both fat depots was higher in patients with obesity and/or type 2 diabetes; in addition, the expression level was significantly associated with insulin resistance. Incubating adipocytes under conditions mimicking the microenvironment of obese adipose tissue, including increased endoplasmic reticulum (ER) stress, induced TRIB3 expression. In human adipocytes, the overexpression of TRIB3 impaired insulin-stimulated protein kinase B (AKT) phosphorylation and caused dysregulation of the transcription of genes encoding bioactive molecules released from adipocytes, such as proinflammatory cytokines, adiponectin, and leptin. Pioglitazone, an insulin-sensitizing agent, reduced both these effects of TRIB3 and the ER stressor-induced expression of TRB3. CONCLUSION: Our data indicate that TRIB3 expression in adipose tissue is enhanced in patients with obesity and suggest that increased TRIB3 dysregulates adipocyte function, which may contribute to the development of insulin resistance.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Gordura Subcutânea Abdominal/metabolismo , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Adulto , Proteínas de Ciclo Celular/análise , Células Cultivadas , Técnicas de Cocultura , Estresse do Retículo Endoplasmático , Feminino , Humanos , Resistência à Insulina , Gordura Intra-Abdominal/citologia , Macrófagos , Pessoa de Meia-Idade , Pioglitazona/farmacologia , Cultura Primária de Células , Proteínas Serina-Treonina Quinases/análise , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Repressoras/análise , Gordura Subcutânea Abdominal/citologia , Regulação para Cima/efeitos dos fármacos
9.
J Clin Med ; 10(21)2021 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-34768610

RESUMO

Trimethylamine N-oxide (TMAO), a gut microbe-dependent metabolite, has been implicated as a novel risk factor for cardiovascular events related to obesity and type 2 diabetes mellitus (T2DM). The aim of the study was to test the hypothesis if TMAO is associated with the reduction of cardiovascular disease in the Korean obese patients who underwent bariatric surgery. From a subgroup of a multicenter, nonrandomized, controlled trial, titled KOBESS, 38 obese patients, 18 with and 20 without T2DM, who underwent Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were investigated. Bariatric surgery is indicated for Korean patients with a body mass index (BMI) ≥ 35 kg/m2 or for Korean patients with a BMI ≥ 30 kg/m2 who have comorbidities. Serum levels of TMAO and its precursors, betaine, carnitine, and choline were measured before and six months after bariatric surgery. The levels of TMAO and its precursors did not differ between obese patients with T2DM and non-T2DM at baseline. However, TMAO increased more than twofold in patients with T2DM after RYGB surgery, but not in patients without T2DM. Choline levels were decreased by half in all patients after RYGB. In patients with T2DM who underwent SG, TMAO, betaine, and carnitine levels did not change after the surgery. Furthermore, in obese patients who underwent bariatric surgery, increased TMAO levels were associated with both T2DM and RYGB, while reduced choline levels were associated with RYGB. These associations need to be further elucidated in follow-up studies to gain further insights into the relationship between TMAO levels and bariatric surgery outcomes.

10.
Ann Surg Treat Res ; 101(4): 197-205, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34692591

RESUMO

PURPOSE: The aim of this study was to show that bariatric surgery (BS) is more effective than medical therapy (MT) in Asian obese patients. METHODS: In this prospective, multicenter, nonrandomized, controlled trial, obese patients with body mass index of ≥35 kg/m2 or 30.0-34.9 kg/m2 with obesity-related comorbidities were assigned to undergo BS, such as laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass, or MT. Patients who underwent BS were evaluated 4, 12, 24, and 48 weeks after surgery, whereas patients who received MT were monitored at a hospital every 6 weeks for 1 year. At each visit, weight, waist and hip circumference, and blood pressure were measured, and patients underwent physical examination and laboratory testing. Health-related quality of life (HQOL) was investigated using Euro QOL-5 Dimension, Impact of Weight on Quality of Life questionnaire-Lite and Obesity-related Problems scale. RESULTS: The study included 264 patients from 13 institutions; of these, 64 underwent BS and 200 received MT. Of the patients who underwent BS, 6.3% experienced early complications. Relative weight changes from baseline to 48 weeks were significantly greater in the BS than in the MT group (26.9% vs. 2.1%, P < 0.001), as were the rates of remission of diabetes (47.8% vs. 16.7%, P = 0.014), hypertension (60.0% vs. 26.1%, P < 0.001), and dyslipidemia (63.2% vs. 22.0%, P < 0.001). HQOL was better in the BS than in the MT group at 48 weeks. CONCLUSION: BS was safe and effective in Korean obese patients, with greater weight reduction, remission of comorbidities, and quality of life improvement than MT.

12.
Metabolomics ; 17(8): 71, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34355282

RESUMO

INTRODUCTION: Bariatric surgery is known to be the most effective treatment for weight loss in obese patients and for the rapid remission of obesity-related comorbidities. These short-term improvements result from not only limited digestion or absorption but also dynamic changes in metabolism throughout the whole body. However, short-term metabolism studies associated with bariatric surgery in Asian individuals have not been reported. OBJECTIVES: The aim of this study was to investigate the short-term metabolome changes in the serum promoted by laparoscopic sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB) and to determine the underlying mechanisms that affect obesity-related comorbidities. METHODS: Serum samples were collected from Korean patients who underwent RYGB or SG before and 4 weeks after the surgery. Metabolomic and lipidomic profiling was performed using UPLC-Orbitrap-MS, and data were analyzed using statistical analysis. RESULTS: Metabolites mainly related to amino acids, lipids (fatty acids, glycerophospholipids, sphingolipids, glycerolipids) and bile acids changed after surgery, and these changes were associated with the lowering of risk factors for obesity-related diseases such as nonalcoholic fatty liver disease (NAFLD), type 2 diabetes (T2D) and atherosclerosis. Interestingly, the number of significantly altered metabolites related to the lipid metabolism were greater in SG than in RYGB. Furthermore, the metabolites related to amino acid metabolism were significantly changed only after SG, whereas bile acid changed significantly only following RYGB. CONCLUSION: These differences could result from anatomical differences between the two surgeries and could be related to the gut microbiota. This study provides crucial information to expand the knowledge of the common but different molecular mechanisms involved in obesity and obesity-related comorbidities affected by each bariatric procedure.


Assuntos
Cirurgia Bariátrica , Metaboloma , Obesidade , Adulto , Aterosclerose/sangue , Aterosclerose/epidemiologia , Aterosclerose/metabolismo , Comorbidade , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Gastrectomia , Derivação Gástrica , Humanos , Laparoscopia , Lipidômica , Masculino , Metaboloma/fisiologia , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/sangue , Obesidade/epidemiologia , Obesidade/metabolismo , Obesidade/cirurgia , Período Perioperatório , Estudos Prospectivos , República da Coreia/epidemiologia , Fatores de Risco
13.
J Clin Med ; 10(8)2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33924059

RESUMO

BACKGROUND: Perforated peptic ulcer (PPU) is a disease whose incidence is decreasing. However, PPU still requires emergency surgery. The aim of this study was to review the clinical characteristics of patients who received primary repair for PPU and identify the predisposing factors associated with severe complications. METHOD: From January 2011 to December 2020, a total of 75 patients underwent primary repair for PPU in our hospital. We reviewed the patients' data, including general characteristics and perioperative complications. Surgical complications were evaluated using the Clavien-Dindo Classification (CDC) system, with which we classified patients into the mild complication (CDC 0-III, n = 61) and severe complication (CDC IV-V, n = 14) groups. RESULT: Fifty patients had gastric perforation, and twenty-five patients had duodenal perforation. Among surgical complications, leakage or fistula were the most common (5/75, 6.7%), followed by wound problems (4/75, 5.3%). Of the medical complications, infection (9/75, 12%) and pulmonary disorder (7/75, 9.3%) were common. Eight patients died within thirty days after surgery (8/75, 10.7%). Liver cirrhosis was the most significant predisposing factor for severe complications (HR = 44.392, p = 0.003). CONCLUSION: PPU is still a surgically important disease that has significant mortality, above 10%. Liver cirrhosis is the most important underlying disease associated with severe complications.

14.
J Am Coll Surg ; 232(6): 973-981.e2, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33831541

RESUMO

BACKGROUND: We investigated whether preoperative clinical parameters predict diabetes remission and relapse after conventional gastrectomy for cancer and whether postoperative weight changes influence diabetes remission and relapse. STUDY DESIGN: This study included 5,150 patients with diabetes who underwent gastrectomy for cancer from 2004 to 2014. Diabetes remission was defined in 3 ways, according to postoperative antidiabetic medication and fasting plasma glucose (FPG) levels. Diabetes relapse was defined as reinitiating antidiabetic medication among patients in diabetes remission. RESULTS: Six predictors (higher body mass index [BMI], total gastrectomy, younger age, FPG levels, number of oral hypoglycemic agents [OHAs], and no insulin use) of diabetes remission increased the likelihood of remission by >13-fold (odds ratio [OR], 13.67; 95% confidence interval [CI], 8.65‒19.11). Three factors (younger age, lower FPG levels, and use of only 1 OHA) predicted a 58% decreased likelihood of diabetes relapse (hazard ratio, 0.42; 95% CI 0.35‒0.48). The lowest interval of postoperative BMI decrease (<-20%) showed a >3-fold increased likelihood of diabetes remission than the highest interval (≥-5%; OR 3.14; 95% CI 2.08‒4.75), independent of baseline BMI. CONCLUSIONS: Six variables (BMI, type of gastrectomy, age, FPG levels, number of OHAs used, and insulin use/non-use), and 3 variables (age, FPG levels, number of OHAs used) significantly predict diabetes remission and relapse after gastrectomy for cancer, respectively. Greater postoperative weight decrease may increase the likelihood of diabetes remission, independent of baseline weight. Our results may serve as a basis for the establishment of diabetes and weight management strategies after conventional gastrectomy for cancer.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Gastrectomia/estatística & dados numéricos , Hipoglicemiantes/uso terapêutico , Neoplasias Gástricas/cirurgia , Redução de Peso , Idoso , Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Seguimentos , Gastrectomia/efeitos adversos , Gastrectomia/métodos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Recidiva , República da Coreia/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento
15.
Nat Metab ; 3(3): 410-427, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33758420

RESUMO

TFEB, a key regulator of lysosomal biogenesis and autophagy, is induced not only by nutritional deficiency but also by organelle stress. Here, we find that Tfeb and its downstream genes are upregulated together with lipofuscin accumulation in adipose tissue macrophages (ATMs) of obese mice or humans, suggestive of obesity-associated lysosomal dysfunction/stress in ATMs. Macrophage-specific TFEB-overexpressing mice display complete abrogation of diet-induced obesity, adipose tissue inflammation and insulin resistance, which is independent of autophagy, but dependent on TFEB-induced GDF15 expression. Palmitic acid induces Gdf15 expression through lysosomal Ca2+-mediated TFEB nuclear translocation in response to lysosomal stress. In contrast, mice fed a high-fat diet with macrophage-specific Tfeb deletion show aggravated adipose tissue inflammation and insulin resistance, accompanied by reduced GDF15 level. Finally, we observe activation of TFEB-GDF15 in ATMs of obese humans as a consequence of lysosomal stress. These findings highlight the importance of the TFEB-GDF15 axis as a lysosomal stress response in obesity or metabolic syndrome and as a promising therapeutic target for treatment of these conditions.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Fator 15 de Diferenciação de Crescimento/metabolismo , Resistência à Insulina , Lisossomos/metabolismo , Obesidade/prevenção & controle , Estresse Fisiológico , Tecido Adiposo/metabolismo , Animais , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Humanos , Macrófagos/metabolismo , Camundongos , Camundongos Transgênicos , Obesidade/metabolismo
16.
Surg Obes Relat Dis ; 17(7): 1359-1368, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33753007

RESUMO

We previously reported that the duodenal-jejunal bypass (DJB) surgery altered transsulfuration and purine metabolism via flux changes in 1-carbon metabolism in the liver. In this study, we extended our study to gain further insight into mechanistic details of how the DJB-induced flux changes in 1-carbon metabolism contributes to the improvement of diet-induced nonalcoholic fatty liver disease. Rodents were subjected to surgical (sham operation and DJB) or dietary (reduced food supply to follow the weight changes in the DJB group) interventions. The microscopic features of the liver were examined by immunohistochemistry. The expressions of genes in lipid synthesis and in 1-carbon cycle in the liver were analyzed by real-time polymerase chain reaction and western blotting. Metabolic changes in the liver were determined. We observed that DJB reduces hepatic steatosis and improves insulin sensitivity in both high-fat diet-fed rats and mice. Metabolic analyses revealed that the possible underlying mechanism may involve decreased S-adenosylmethionine (SAM)-to-S-adenosylhomocysteine ratio via downregulation of SAM synthesizing enzyme and upregulation of SAM catabolizing enzyme. We also found in mice that DJB-mediated attenuation of hepatic steatosis is independent of weight loss. DJB also increased hepatic expression levels of GNMT while decreasing those of PEMT and BHMT, a change in 1-carbon metabolism that may decrease the ratio of SAM to S-adenosylhomocysteine, thereby resulting in the prevention of fat accumulation in the liver. Thus, we suggest that the change in 1-carbon metabolism, especially the SAM metabolism, may contribute to the improvement of diet-induced fatty liver disease after DJB surgery.


Assuntos
Homocisteína , S-Adenosilmetionina , Animais , Dieta Hiperlipídica , Duodeno , Jejuno , Fígado , Camundongos , Obesidade/etiologia , Obesidade/cirurgia , Fosfatidiletanolamina N-Metiltransferase , Ratos
17.
Obes Surg ; 31(4): 1485-1495, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33411317

RESUMO

PURPOSE: Recently, more than 10 models have been developed to predict remission of type 2 diabetes mellitus (T2DM) after metabolic surgery. The ABCD score was compared to the individualized metabolic surgery (IMS) score in terms of prediction of T2DM remission, but which of the two scoring systems is better remains controversial. METHODS: Patient data from 463 obese East Asian patients who underwent laparoscopic Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG), or SG with duodenojejunal bypass (SG-DJB) as a primary operation and were followed for at least 3 years were retrospectively collected from 24 institutions. The correlation between the ABCD and IMS scoring systems and the discrimination power of the models was evaluated. The cut-off point for the IMS stage of T2DM severity was also revised to adjust the scoring system to obese East Asian patients. RESULTS: The two scoring systems were significantly well correlated. The IMS scoring system showed significant differences in T2DM remission rates between the procedures in the moderate stage, but the ABCD score showed no significant differences in each category. The discrimination power of the IMS score was comparable to that of the ABCD score at both 3 and 5 years. The revised IMS scoring system showed that SG-DJB had significantly higher T2DM remission rates in the moderate stage at 5 years than RYGB or SG. CONCLUSION: IMS score may be comparable to ABCD score to predict T2DM remission in obese East Asian patients. The revised IMS scoring system may also select candidates for SG or SG-DJB.


Assuntos
Cirurgia Bariátrica , Diabetes Mellitus Tipo 2 , Derivação Gástrica , Obesidade Mórbida , Diabetes Mellitus Tipo 2/cirurgia , Gastrectomia , Humanos , Obesidade/cirurgia , Obesidade Mórbida/cirurgia , Estudos Retrospectivos , Resultado do Tratamento
18.
J Clin Med ; 9(12)2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-33271740

RESUMO

BACKGROUND: Amino acid metabolites (AAMs) have been linked to glucose homeostasis and type 2 diabetes (T2D). We investigated whether (1) baseline AAMs predict T2D remission 12 months after bariatric surgery and (2) whether AAMs are superior for predicting T2D remission postoperatively compared with existing prediction models. METHODS: Among 24 participants undergoing bariatric surgery, 16 diabetes-related AAMs were quantified at baseline and postoperative 3 and 12 months. Existing prediction models included the ABCD, DiaRem, and IMS models. RESULTS: Baseline L-dihydroxyphenylalanine (L-DOPA) (areas under receiver operating characteristic curves (AUROC), 0.92; 95% confidence interval (CI), 0.75 to 1.00) and 3-hydroxyanthranilic acid (3-HAA) (AUROC, 0.85; 95% CI, 0.67 to 1.00) better predicted T2D remission 12 months postoperatively than the ABCD model (AUROC, 0.81; 95% CI, 0.54 to 1.00), which presented the highest AUROC value among the three models. The superior prognostic performance of L-DOPA (AUROC at 3 months, 0.97; 95% CI, 0.91 to 1.00) and 3-HAA (AUROC at 3 months, 0.86; 95% CI, 0.63 to 1.00) continued until 3 months postoperatively. CONCLUSIONS: The AAM profile predicts T2D remission after bariatric surgery more effectively than the existing prediction models.

19.
Int J Obes (Lond) ; 44(3): 697-706, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31965068

RESUMO

BACKGROUND: This study investigated depot-specific mRNA expression of uncoupling protein 1 (UCP1) in human white adipose tissue (WAT) and its association with obesity-related markers. METHODS: We recruited 39 normal-weight, 41 nondiabetic obese, and 22 diabetic obese women. We measured UCP1 mRNA expression in abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), and investigated the associations between UCP1 mRNA expression in VAT and SAT, and obesity-related markers including mRNA expression of leptin, adiponectin, CCAAT-enhancer-binding protein homologous protein (CHOP), and positive regulatory domain-containing protein 16 (PRDM16). We also evaluated UCP1 mRNA expression in differentiated human white adipocytes after treatment with various stressors and metabolic improvement agents in vitro. RESULTS: UCP1 mRNA in VAT was significantly higher than in SAT in all groups. UCP1 mRNA in SAT was negatively correlated with BMI, total abdominal fat area, visceral fat area, blood pressure, fasting glucose, insulin, HOMA-IR score, triglyceride, hsCRP, fasting leptin levels, and adipocyte size. UCP1 mRNA in SAT was positively correlated with fasting adiponectin levels. UCP1 mRNA in VAT was negatively correlated with visceral-to-subcutaneous fat ratio (VSR), fasting glucose, and triglyceride levels. In SAT, UCP1 mRNA was negatively correlated with mRNA expression of leptin and CHOP, and positively correlated with mRNA expression of adiponectin. The expression of PRDM16 was positively correlated with UCP1 mRNA in both VAT and SAT. UCP1 mRNA expression in differentiated human white adipocytes was significantly reduced after incubation with thapsigargin, tunicamycin, homocysteine, TNF-α, or IL-ß, and significantly increased after incubation with exendin 4, dapagliflozin, and telmisartan. CONCLUSIONS: This study demonstrated depot-specific mRNA expression of UCP1 and its association with obesity-related markers in human WAT. UCP1 mRNA in human white adipocytes was suppressed by inflammatory agents and enhanced by metabolic improvement agents. UCP1 in human WAT might participate in the pathogenesis of obesity-related metabolic diseases.


Assuntos
Tecido Adiposo Branco/metabolismo , Obesidade/metabolismo , Proteína Desacopladora 1 , Adipócitos/metabolismo , Adulto , Biomarcadores/metabolismo , Células Cultivadas , Estresse do Retículo Endoplasmático/fisiologia , Feminino , Humanos , Inflamação/metabolismo , Resistência à Insulina/fisiologia , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , Proteína Desacopladora 1/análise , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismo
20.
Obes Surg ; 30(1): 256-266, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31396789

RESUMO

OBJECTIVE: This study aimed to evaluate the cost-effectiveness of bariatric surgery (BS) compared to non-surgical treatment (NST) in Korean people with morbid obesity according to comorbidities and body mass index (BMI) severity. METHODS: The target cohort was people with morbid obesity, defined as BMI of ≥ 35 kg/m2, or obese people with BMI of 30-34.9 kg/m2 having obesity-related comorbidities. A decision-tree model for 1-year obesity treatment and Markov model for the rest of life were used. In the decision-tree model, the comorbidity remission rate and BMI change after 1-year treatment were decided based on a prospective clinical trial. In the Markov model, the transition probabilities were calculated considering the BMI level and age. The starting age of 20 years, a cycle length of 1 year, a time horizon of 80 years, and a 5% discount rate were applied for the base case from the healthcare system perspective. RESULTS: In the base case, BS improved quality-adjusted life years (QALYs) and was the cost-effective option in total cohort (incremental cost-effectiveness ratio of BS vs. NST was 674 USD/QALY). It was shown to be cost-effective in all subgroup analyses based on BMI level. In particular, BS was a dominant alternative for the subgroup with basal BMI of 35.0-37.4 kg/m2. Various sensitivity analyses showed the robustness of results indicating the cost-effectiveness of BS. CONCLUSION: BS at BMI of > 30 kg/m2 was more effective than NST for a reduction in BMI and remission of obesity-related comorbidities and was cost-effective in Korea.


Assuntos
Cirurgia Bariátrica , Obesidade Mórbida/economia , Obesidade Mórbida/cirurgia , Adulto , Cirurgia Bariátrica/efeitos adversos , Cirurgia Bariátrica/economia , Cirurgia Bariátrica/métodos , Cirurgia Bariátrica/estatística & dados numéricos , Índice de Massa Corporal , Estudos de Coortes , Comorbidade , Análise Custo-Benefício , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/epidemiologia , Estudos Prospectivos , Anos de Vida Ajustados por Qualidade de Vida , República da Coreia/epidemiologia
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