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ABSTRACT: To compare endocrine, metabolic, and inflammatory changes induced by gastric bypass (GB) and sleeve gastrectomy (SG) in patients with type 2 diabetes mellitus (T2DM), and to investigate the mechanisms of success after metabolic surgery. Sixteen GB and 16 SG patients were followed up before and at 1 year after surgery. The 75-g oral glucose tolerance test (OGTT) was performed before and after surgery. Glucose homeostasis, serum interleukin-1β, plasma gut hormones and adipokines, and the United Kingdom Prospective Diabetes Study (UKPDS) ten-year cardiovascular risks were evaluated. The diabetes remission rate was significantly higher in GB than SG. Changes in the area under the curve (AUC) for glucose were greater in those with complete and partial remission after GB and remitters after SG than non-remitters after SG, whereas changes in AUC for C-peptide were higher in complete and partial remitters after GB than non-remitters after SG. Insulinogenic index was enhanced and serum interleukin-1β was reduced in complete remitters after GB and remitters after SG. Logistic regression analysis confirmed that insulinogenic index and interleukin-1β not insulin resistance, were the factors determining the success of diabetes remission after metabolic surgeries. GB and SG significantly reduced the ten-year risk of coronary heart disease and fatal coronary heart disease in T2DM patients after surgery, while GB had the additional benefit of reduced stroke risk. Human diabetes remission after metabolic surgery is through insulin secretion and interleukin-1β dependent mechanisms. GB is superior to SG in cardiocerebral risk reduction in Asian non-morbidly obese T2DM patients.
Current Medicinal Chemistry 03/2013; · 4.86 Impact Factor
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ABSTRACT: Hyperuricemia is closely associated with obesity and metabolic abnormalities, which is also an independent risk factor for cardiovascular diseases. The PPARγ gene, which is linked to obesity and metabolic abnormalities in Han Chinese, might be considered a top candidate gene that is involved in hyperuricemia. This study recruited 457 participants, aged 20-40 years old, to investigate the associations of the PPARγ gene and metabolic parameters with hyperuricemia. Three tag-single nucleotide polymorphisms, rs2292101, rs4684846, and rs1822825, of the PPARγ gene were selected to explore their association with hyperuricemia. Risk genotypes on rs1822825 of the PPARγ gene exhibited statistical significance with hyperuricemia (odds ratio: 1.9; 95% confidence interval: 1.05-3.57). Although gender, body mass index (BMI), serum total cholesterol concentration, or protein intake per day were statistically associated with hyperuricemia, the combination of BMI, gender, and rs1822825, rather than that of age, serum lipid profile, blood pressure, and protein intake per day, satisfied the predictability for hyperuricemia (sensitivity: 69.3%; specificity: 83.7%) in Taiwan-born obese Han Chinese. BMI, gender, and the rs1822825 polymorphism in the PPARγ gene appeared good biomarkers in hyperuricemia; therefore, these powerful indicators may be included in the prediction of hyperuricemia to increase the accuracy of the analysis.
Genetic Testing and Molecular Biomarkers 01/2013; 17(1):40-6. · 1.11 Impact Factor
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ABSTRACT: BACKGROUND: Hyperuricemia is associated with obesity. Few studies have reported the effects of different types of bariatric surgery on uric acid metabolism. The aim of our study was to determine the relationships between serum uric acid reduction and estrogen receptor-α (ESR1) gene polymorphism, as well as the type of bariatric surgery received. The potential physiological pathways involved in postsurgery serum uric acid reduction were also discussed. METHODS: A total of 508 severely obese Han Chinese patients, aged 20 to 50 years, with a body mass index (BMI)≥35 kg/m(2) were selected. Patients received either laparoscopic adjustable gastric banding (LAGB; n = 164) or laparoscopic mini-gastric bypass (LMGB; n = 344). A 12-month follow-up was performed to explore the effects of the type of bariatric surgery and ESR1 polymorphism on serum uric acid reduction. RESULTS: The rs712221 polymorphism of ESR1 affects serum uric acid reduction after bariatric surgery. The LMGB group exhibited a greater reduction in serum uric acid level compared with the LAGB counterpart after adjusting for sex, age, and metabolic confounders (-2.3±2.1 mg/dL versus-1.2±1.1 mg/dL; P = .002). Patients with the rs712221 genotype exhibited better glycemic control and a greater serum uric acid reduction at 12 months after surgery. The effects of the rs712221 polymorphism in LMGB patients resulted in the greatest serum uric acid reduction (-2.7±1.4 mg/dL). CONCLUSIONS: For severely obese Han Chinese patients, bariatric surgery appears to reduce serum uric acid levels, potentially mediated by synergic effects of surgery type, BMI reduction, rs712221 locus, insulin sensitivity, and changed dietary factors via an unknown mechanism.
Surgery for Obesity and Related Diseases 11/2012; · 3.93 Impact Factor
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ABSTRACT: Background/Aims: Nutrition problems caused by laparoscopic mini-gastric bypass surgery (LMGB) include lack of iron, calcium and poor nutrition. Iron deficiency anemia is the common. The purpose of this study was to investigate why our patients' hemoglobin level was at a low value after surgery and the relationship between diet frequency, diet behavior, and low hemoglobin level. Methodology: From January 2009 to April 2010, 120 patients who received laparoscopic mini-gastric bypass surgery were included in this study. Among all patients, there were 34 men and 86 women. Hemoglobin level of male patients less than 13mg/dL and that of female patients less than 11.5mg/dL was defined as anemia. The clinical characteristics and diet behavior were analyzed. Results: The mean age was 30.9±10.5 years and the mean body mass index was 41.4±7.2kg/m2. Before and after surgery, the proportion of anemia was 4.1% and 26.6%, respectively. The proportion of anemia in females increased more than in males. Hemoglobin level after surgery showed positive correlation (p<0.05) with the diet frequency of high protein, sugar drinks with balanced formula, alcoholic drinks and exercise, but negative correlation (p<0.01) with iron supplements. Conclusions: The study concluded that patients after laparoscopic mini-gastric bypass surgery should increase the ingestion of high-protein drinks or food, alcoholic drinks and exercise, to prevent a low hemoglobin level.
Hepato-gastroenterology 11/2012; 59(120):2530-2. · 0.66 Impact Factor
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ABSTRACT: BACKGROUND: Obesity is a risk factor for developing chronic kidney disease (CKD) that may be improved with bariatric surgical weight reduction. The objective of this study was to investigate changes in the glomerular filtration rate (GFR) in severely obese patients 1 year after bariatric surgery. METHODS: GFR was measured in 233 severely obese patients before and more than 12 months after bariatric surgery. Patients were separated by baseline GFR: hyperfiltration (GFR>125 mL/min), normal (GFR 125-90 mL/min), CKD stage 2 (GFR 89-60 mL/min), and CKD stage 3 (59-30 mL/min). The groups were reanalyzed 12 months after bariatric surgery. RESULTS: Of the 233 patients, 61 (26.2%) had hyperfiltration, 127 (54.5%) were normal, 39 (16.7%) had CKD stage 2, and 6 (2.6%) had CKD stage 3. The mean GFR was 146.4±17.1 mL/min in the hyperfiltration group, 105.7±9.6 mL/min in the normal group, 76.8±16.7 mL/min in the CKD stage 2 group, and 49.5±6.6 mL/min in the CKD stage 3 group. The mean GFR 1 year after weight loss surgery decreased to 133.9±25.7 mL/min in the hyperfiltration group, increased to 114.2±22.2 mL/min in the normal group, increased to 93.3±20.4 mL/min in the CKD stage 2 group, and increased to 66.8±19.3 mL/min in the CKD stage 3 group. CONCLUSIONS: Abnormal renal function was common in severely obese patients. Bariatric surgery-induced weight loss had positive effects on renal function at 1 year after surgery.
Surgery for Obesity and Related Diseases 10/2012; · 3.93 Impact Factor
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ABSTRACT: OBJECTIVE
To find clinically meaningful preoperative predictors of diabetes remission and conversely inadequate glycemic control after gastric bypass surgery. Predicting the improvement in glycemic control in those with type 2 diabetes after bariatric surgery may help in patient selection.RESEARCH DESIGN AND METHODS
Preoperative details of 154 ethnic Chinese subjects with type 2 diabetes were examined for their influence on glycemic outcomes at 1 year after gastric bypass. Remission was defined as HbA(1c) ≤6%. Analysis involved binary logistic regression to identify predictors and provide regression equations and receiver operating characteristic curves to determine clinically useful cutoff values.RESULTSRemission was achieved in 107 subjects (69.5%) at 12 months. Diabetes duration <4 years, body mass >35 kg/m(2), and fasting C-peptide concentration >2.9 ng/mL provided three independent preoperative predictors and three clinically useful cutoffs. The regression equation classification plot derived from continuous data correctly assigned 84% of participants. A combination of two or three of these predictors allows a sensitivity of 82% and specificity of 87% for remission. Duration of diabetes (with different cutoff points) and C-peptide also predicted those cases in which HbA(1c) ≤7% was not attained. Percentage weight loss after surgery was also predictive of remission and of less satisfactory outcomes.CONCLUSIONS
The glycemic response to gastric bypass is related to BMI, duration of diabetes, fasting C-peptide (influenced by insulin resistance and residual β-cell function), and weight loss. These data support and refine previous findings in non-Asian populations. Specific ethnic and procedural regression equations and cutoff points may vary.
Diabetes care 10/2012; · 8.09 Impact Factor
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ABSTRACT: BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is considered the gold standard for the treatment of morbid obesity but is technically challenging and results in significant perioperative complications. While laparoscopic mini-gastric bypass (LMGB) has been reported to be a simple and effective treatment for morbid obesity, controversy exists. Long-term follow-up data from a large number of patients comparing LMGB to LRYGB are lacking. METHODS: Between October 2001 and September 2010, 1,657 patients who received gastric bypass surgery (1,163 for LMGB and 494 for LRYGB) for their morbid obesity were recruited from our comprehensive obesity surgery center. Patients who received revision surgeries were excluded. Minimum follow-up was 1 year (mean 5.6 years, from 1 to 10 years). The operative time, estimated blood loss, length of hospital stay, and operative complications were assessed. Late complication, changes in body weight loss, BMI, quality of life, and comorbidities were determined at follow-up. Changes in quality of life were assessed using the Gastrointestinal Quality of Life Index. RESULTS: There was no difference in preoperative clinical parameters between the two groups. Surgical time was significantly longer for LRYGB (159.2 vs. 115.3 min for LMGB, p < 0.001). The major complication rate was borderline higher for LRYGB (3.2 vs. 1.8 %, p = 0.07). At 5 years after surgery, the mean BMI was lower in LMGB than LRYGB (27.7 vs. 29.2, p < 0.05) and LMGB also had a higher excess weight loss than LRYGB (72.9 vs. 60.1 %, p < 0.05). Postoperative gastrointestinal quality of life increased significantly after operation in both groups without any significant difference at 5 years. Obesity-related clinical parameters improved in both groups without significant difference, but LMGB had a lower hemoglobin level than LRYGB. Late revision rate was similar between LRYGB and LMGB (3.6 vs. 2.8 %, p = 0.385). CONCLUSIONS: This study demonstrates that LMGBP can be regarded as a simpler and safer alternative to LRYGB with similar efficacy at a 10-year experience.
Obesity Surgery 09/2012; · 3.29 Impact Factor
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ABSTRACT: Background/Aims: Hepatic progenitor cells (HPCs) activation, proliferative ductular reaction (DR), replicative arrest and Notch signaling have been demonstrated in a variety of human liver diseases. The relationships are poorly understood in morbid obesity. We investigated factors responsible for the HPCs/DR, replicative arrest and Notch signaling in non-NASH and NASH groups. Methodology: Cytokeratin 7 (and 19), p21, CD34, Ki67 and different Notch receptors and ligands immunohistochemical stained biopsies from morbid obese patients with non-NASH (n=10) and NASH (n=25) were studied. These results were correlated with clinicopathological variables. Results: NASH patients presented with abnormal liver function tests and had higher HbA1c percentage. Strong association between HPCs and DR was seen (r=0.785, p<0.000). BMI, interface activity and replicative arrest were associated with HPCs expansion and DR in NASH patients. A strong association between CD34 with HPCs and DR was found in non-NASH patients. In NASH group, Notch 3 was important in bile ductular proliferation; whereas Notch 4 was associated with sinusoidal neovessels proliferation and Kupffer cell activation. Conclusions: HPCs and DR played an important role in hepatic regeneration in fatty liver disease of morbid obesity. An altered replication pathway in NASH promotes HPCs activation and DR. Notch-3 and Notch-4 were significantly different between non-NASH and NASH groups.
Hepato-gastroenterology 09/2012; 59(118):1921-7. · 0.66 Impact Factor
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ABSTRACT: BACKGROUND: Surgery is the most effective treatment of morbid obesity and leads to dramatic improvements in type 2 diabetes mellitus (T2DM). Gastrointestinal metabolic surgery has been proposed as a treatment option for T2DM. However, a grading system to categorize and predict the outcome of metabolic surgery is lacking. The study setting was a tertiary referral hospital (Taoyuan City, Taoyuan County, Taiwan). METHODS: We first evaluated 63 patients and identified 4 factors that predicted the success of T2DM remission after bariatric surgery in this cohort: body mass index, C-peptide level, T2DM duration, and patient age. We used these variables to construct the Diabetes Surgery Score, a multidimensional 10-point scale along which greater scores indicate a better chance of T2DM remission. We then validated the index in a prospective collected cohort of 176 patients, using remission of T2DM at 1 year after surgery as the outcome variable. RESULTS: A total of 48 T2DM remissions occurred among the 63 patients and 115 remissions (65.3%) in the validation cohort. Patients with T2DM remission after surgery had a greater Diabetes Surgery Score than those without (8 ± 4 versus 4 ± 4, P < .05). Patients with a greater Diabetes Surgery Score also had a greater rate of success with T2DM remission (from 33% at score 0 to 100% at score 10); A 1-point increase in the Diabetes Surgery Score translated to an absolute 6.7% in the success rate. CONCLUSION: The Diabetes Surgery Score is a simple multidimensional grading system that can predict the success of T2DM treatment using bariatric surgery among patients with inadequately controlled T2DM.
Surgery for Obesity and Related Diseases 08/2012; · 3.93 Impact Factor
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Yi-Cheng Chang,
Yen-Feng Chiu,
I-Te Lee,
Low-Tone Ho,
Yi-Jen Hung,
Chao A Hsiung,
Thomas Quertermous,
Timothy Donlon, Wei-Jei Lee,
Po-Chu Lee,
Che-Hong Chen,
Daria Mochly-Rosen,
Lee-Ming Chuang
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ABSTRACT: Genetic variants near/within the ALDH2 gene encoding the mitochondrial aldehyde dehydrogenase 2 have been associated with blood pressure and hypertension in several case-control association studies in East Asian populations.
Three common tag single nucleotide polymorphisms (tagSNP) in the ALDH2 gene were genotyped in 1,134 subjects of Chinese origin from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) family cohort. We examined whether the ALDH2 SNP genotypes predicted the development of hypertension in the prospective SAPPHIRe cohort.
Over an average follow-up period of 5.7 years, carriers homozygous for the rs2238152 T allele in the ALDH2 gene were more likely to progress to hypertension than were non-carriers (hazard ratio [HR], 2.88, 95% confidence interval [CI], 1.06-7.84, P = 0.03), corresponding to a population attributable risk of ~7.1%. The risk associated with the rs2238152 T allele were strongest in heavy/moderate alcohol drinkers and was reduced in non-drinkers, indicating an interaction between ALDH2 genetic variants and alcohol intake on the risk of hypertension (P for interaction = 0.04). The risk allele was associated with significantly lower ALDH2 gene expression levels in human adipose tissue.
ALDH2 genetic variants were associated with progression to hypertension in a prospective Chinese cohort. The association was modified by alcohol consumption.
BMC Cardiovascular Disorders 07/2012; 12:58. · 1.52 Impact Factor
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ABSTRACT: Anemia is the most common nutritional deficiency after bariatric surgery. The predictors of anemia have not been clearly identified. This issue is useful for selecting an appropriate surgery procedure for morbid obesity.
From December 2000 to October 2007, a retrospective study of 442 obese patients after bariatric surgery with two years' follow-up data was conducted. Anemia was defined by hemoglobin (Hb) under 13mg/dL in male and 11.5mg/dL in female. We analyzed the clinical information and laboratory data during the initial evaluation of patients referred to bariatric surgery for predictors of anemia development after surgery. All data were analyzed by using multivariate adaptive regression splines (MARS) method.
Of the patients, the mean age was 30.8±8.6 years; mean BMI was 40.7±7.8kg/m2 and preoperative mean hemoglobin (Hb) was 13.7±1.5g/ dL. The prevalence of anemia increased from preoperatively 5.4% to 38.0% two years after surgery. Mean Hb was significantly lower in patients receiving gastric bypass than in restrictive type surgery (11.9mg/dL vs. 13.1mg/dL, p=0.040) two years after surgery. Besides, the preoperative optimal value of hemoglobin to predict future anemia in MARS model is 15.6mg/dL.
The prevalence of anemia increased to 38.0% two years after bariatric surgery. We obtained an optimal preoperative value of hemoglobin 15.6mg/dL to predict postoperative anemia, which was important in preoperative assessment for bariatric surgery. Patients undergone gastric bypass surgery developed more severe anemia than gastric banding or sleeve gastrectomy.
Hepato-gastroenterology 07/2012; 59(117):1378-80. · 0.66 Impact Factor
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Yi-Cheng Chang,
Pi-Hua Liu,
Yun-Chih Tsai,
Yen-Feng Chiu,
Shyang-Rong Shih,
Low-Tone Ho,
Wen-Jane Lee,
Chieh-Hua Lu,
Thomas Quertermous,
J David Curb, Wei-Jei Lee,
Po-Chu Lee,
You-Han He,
Jih-I Yeh,
Juey-Jen Hwang,
Shu-Huei Tsai,
Lee-Ming Chuang
Journal of Molecular Medicine 05/2012; · 4.67 Impact Factor
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ABSTRACT: Obestatin, which is a putative 23-amino-acid peptide, is derived from the C-terminal part of the mammalian preproghrelin gene. Nesfatin-1 mRNA is co-expressed with ghrelin in gastric endocrine X/A-like cells; therefore, nesfatin-1 may also interact with preproghrelin gene products in the stomach. In this study, we investigated the impact of obestatin on the plasma levels of acyl ghrelin, des-acyl ghrelin and nesfatin-1, and on the gastric emptying of a solid nutrient meal 2 h after an intracerebroventricular (ICV) injection in conscious, fasted rats. The rats were implanted with ICV catheters. Plasma levels of acyl ghrelin, des-acyl ghrelin and nesfatin-1, expected to be co-expressed with obestatin, were measured, whereas the human/rat corticotropin-releasing factor (h/rCRF) was applied as an inhibitor of gastric emptying. The ICV administration of obestatin (0.1, 0.3 and 1.0 nmol/rat) did not modify the plasma acyl ghrelin and des-acyl ghrelin levels, the acyl ghrelin/des-acyl ghrelin ratio and nesfatin-1 concentrations. The ICV acute administration of obestatin had no influence on the 2-h rate of gastric emptying of a solid nutrient meal, but the ICV h/rCRF injection delayed it. The weight of food ingested 1 h before ICV injection significantly, but negatively correlated with the gastric emptying of a solid nutrient meal. Our study indicates that the ICV injection of obestatin does not change the 2-h rate of gastric emptying of a solid nutrient meal and the relatively weak interrelationships between ghrelin gene products and nesfatin-1. However, the weight of the ingested food negatively affects the gastric emptying of a solid nutrient meal in conscious, fasted rats.
Molecular Medicine Reports 05/2012; 6(1):191-6. · 0.42 Impact Factor
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Yi-Cheng Chang,
Pi-Hua Liu,
Yun-Chih Tsai,
Yen-Feng Chiu,
Shyang-Rong Shih,
Low-Tone Ho,
Wen-Jane Lee,
Chieh-Hua Lu,
Thomas Quertermous,
J David Curb, Wei-Jei Lee,
Po-Chu Lee,
You-Han He,
Jih-I Yeh,
Juey-Jen Hwang,
Shu-Huei Tsai,
Lee-Ming Chuang
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ABSTRACT: Prostaglandins are potent modulators of insulin sensitivity. We systemically evaluated the association of 61 tag single-nucleotide polymorphisms (SNP) in 14 genes involved in prostaglandin metabolism with type 2 diabetes. Among all genotyped SNPs, rs10483032 in the CBR3 (carbonyl reductase 3) gene, which encodes for an enzyme converting prostaglandin E(2) to prostaglandin F2(α), was associated with type 2 diabetes in 760 type 2 diabetic cases and 760 controls (stage-1 study) (P = 2.0 × 10(-4)). The association was validated in 1,615 cases and 1,162 controls (stage-2 study) (P = 0.009). The A allele at rs10483032 was associated with increased risk of type 2 diabetes (odds ratio = 1.29; 95% confidence interval = 1.14-1.47; combined P < 0.0001). The association was externally validated in the Finland-United States Investigation of NIDDM Genetics (FUSION) study (P = 3.7 × 10(-4)). The risk A allele was associated with higher homeostasis model assessment of insulin resistance (HOMA-IR) in 1,012 non-diabetic controls and 1,138 non-diabetic subjects from the Stanford Asia-Pacific Program for Hypertension and Insulin Resistance (SAPPHIRe) family study. CBR3 gene expression in human abdominal adipose tissue was negatively associated with fasting insulin and HOMA-IR. CBR3 gene expression increased during differentiation of 3T3-L1 preadipocytes into adipocytes. Knockdown of CBR3 in 3T3-L1 preadipocytes enhanced adipogenesis and peroxisome proliferator-activator receptor-γ response element reporter activity. Our results indicated that genetic polymorphism in the CBR3 gene conferred risk of type 2 diabetes and insulin resistance in Chinese. The association was probably mediated through modulation of adipogenesis.
Journal of Molecular Medicine 04/2012; 90(7):847-58. · 4.67 Impact Factor
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ABSTRACT: Obesity and type II diabetes mellitus (T2DM) are closely related and difficult to control by current medical treatment. Bariatric surgery has been proposed for inadequately controlled T2DM in association with obesity. However, prediction of successful T2DM remission after surgery has not been clearly studied in Asian patients. This information might be helpful for applying gastrointestinal surgery as metabolic surgery for T2DM.
This was a retrospective clinical study. From January 2002 to December 2008, 88 consecutive patients with morbid obesity, who were enrolled into a surgically supervised weight loss program, and who had T2DM before surgery with at least 1 year complete follow-up data were included. Sixty-eight (77.2%) patients received gastric bypass procedures, and the remaining 20 (22.8%) received restrictive procedures. We analyzed the available information during the initial evaluation of patients who were referred for bariatric surgery, by logistic regression analysis and data mining methods for predictors of successful diabetes remission after surgery.
Overall, 68 (77.2%) of the 88 patients had remission of their T2DM 1 year after surgery. Patients in the bypass group had a higher remission rate than those in the restrictive group [59/68 (86.7%) vs. 9/20 (45.0%), p=0.000]. In univariate analysis, patients who had T2DM remission after surgery were younger, heavier, had a wider waist, less severe disease, shorter duration, and higher C-peptide levels than those without remission. Type of operation and T2DM duration remained independent predictors of success after multivariate logistical regression analysis (p<0.000). Data mining analysis confirmed that T2DM duration was the most important predictor.
Bariatric surgery is a treatment option for T2DM. Duration of diabetes is the most predictor of success after surgery.
Asian Journal of Surgery 04/2012; 35(2):67-73. · 0.57 Impact Factor
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ABSTRACT: The purpose of this study was to investigate the impact of intracerebroventricular (ICV) injection of the two endogenous forms of acyl ghrelin, O-n-octanoylated ghrelin and des-Gln¹⁴-ghrelin, on feeding behavior, as well as their interactions with insulin, obestatin, and corticotropin-releasing factor receptor (CRF-R) antagonist in the forebrain to influence food intake.
We examined the food intake in conscious, freely fed rats, which were chronically implanted with ICV catheters.
O-n-octanoylated ghrelin and des-Gln¹⁴-ghrelin (0.1 nmol/rat) were equally potent in stimulating food intake in freely fed rats, up to 8 h after ICV injection (P < 0.05). In contrast, ICV administration of insulin (8 mU/rat), obestatin (2 nmol/rat), and astressin (2 nmol/rat), a specific CRF-R antagonist, did not modify feeding in freely fed rats. Furthermore, pretreatment with ICV insulin (P < 0.01), but not obestatin or astressin, at the abovementioned dose, blocked central acyl-ghrelin-induced hyperphagic effects.
ICV O-n-octanoylated ghrelin and its splice variant, des-Gln¹⁴-ghrelin, are equally potent to elicit food intake in freely fed rats, while these feeding-stimulating effects are opposed by insulin, but independent of obestatin and endogenous CRF-R in the forebrain.
Nutrition 03/2012; 28(7-8):812-20. · 3.03 Impact Factor
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ABSTRACT: The deadenylase nocturnin (Noc, Ccrn4l) has been recently found to regulate lipid metabolism and to control preadipocyte differentiation. Here, we showed that among the five deadenylases tested, Noc and Pan2 exhibited a biphasic expression which is out of phase to each other during adipocyte differentiation of 3T3-L1 cells. The expression levels of other deadenylases, including Parn, Ccr4, and Caf1, were relatively unchanged or reduced. The immediate early expressed Noc during 3T3-L1 adipogenesis was involved in regulating mitotic clonal expansion (MCE) and cyclin D1 expression, as demonstrated in Noc-silenced 3T3-L1 cells and Noc(-/-) primary mouse embryonic fibroblasts (MEFs). Transcriptional profiling of Noc-depleted 3T3-L1 adipocytes revealed that most of the differentially expressed genes were related to cell growth and proliferation. In human adipose tissue, NOC mRNA level negatively associated with both fasting serum insulin and homeostasis model assessment of insulin resistance, and positively associated with both adiponectin mRNA levels and circulating adiponectin levels. Taken together, these results suggest the role of Noc in the modulation of early adipogenesis as well as systemic insulin sensitivity.
Obesity 02/2012; 20(8):1558-65. · 4.28 Impact Factor
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ABSTRACT: Gastrointestinal metabolic surgery has been proposed for the treatment of not well-controlled type 2 diabetes mellitus (T2DM) patients with a body mass index (BMI) <35 kg/m(2). This study aims to describe recent experience with surgical treatment of T2DM in Asian centers.
Patients aged 20 to 70 years with not well-controlled T2DM [glycated hemoglobin (HbA1C) >7.0%] and BMI < 35 kg/m(2) were included at five institutes between 2007 and 2010. The end point is T2DM remission, defined by fasting plasma glucose <110 mg/dl and HbA1C <6.0%.
Of the 200 patients, 172 (86%) underwent gastric bypass, 24 (12%) underwent sleeve gastrectomy, and the other 4 underwent adjustable banding. Laparoscopic access was used in all the patients. Gender (66.5% female), age (mean 45.0 ± 10.8), and HbA1C (mean 9.3 ± 1.9%) did not differ between the procedure among the groups. Until now, 87 patients had 1-year data. One year after surgery, the mean BMI decreased from 28.5 ± 3.0 to 23.4 ± 2.3 kg/m(2) and HbA1C decreased to 6.3 ± 0.5%. Remission of T2DM was achieved in 72.4% of the patients. Patients with a diabetes duration of <5 years had a better diabetes remission rate than patients with duration of diabetes >5 years (90.3% vs. 57.1%; p = 0.006). Patients with BMI > 30 kg/m(2) had a better diabetes remission rate than those with BMI < 30 kg/m(2) (78.7% vs. 62.5%; p = 0.027). Individuals who underwent gastric bypass loss more weight and had a higher diabetes remission rate than individuals who underwent restrictive-type procedures. Multivariate analysis confirmed that the duration of diabetes and the type of surgery predict the diabetes remission. No mortalities were reported and two (1.0%) patients had major morbidities.
Gastrointestinal metabolic surgery is an effective treatment for not well-controlled T2DM treatment. Diabetes remission is significantly higher in those with duration of diabetes less than 5 years and BMI > 30 kg/m(2).
Journal of Gastrointestinal Surgery 01/2012; 16(1):45-51; discussion 51-2. · 2.83 Impact Factor
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Obesity Surgery 12/2011; · 3.29 Impact Factor
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ABSTRACT: C-peptide is a surrogate of the pancreatic beta cell mass. However, the clinical significance of C-peptide in a diabetic patient after bariatric surgery has not been studied clearly.
From February 2005 to January 2009, a total of 205 (124 females and 81 males) consecutive morbidly obese patients with type 2 diabetes mellitus (T2DM) enrolled in a surgically supervised weight loss program with at least 1 year follow-up were examined. Among them, 147 patients (71.7%) received gastric bypass procedures, while the other 58 patients (28.3%) received restrictive-type procedures.
The mean C-peptide before the surgery was 5.3 ± 3.5 ng/ml. One hundred nineteen patients (58.0%) had an elevated C-peptide (>4 ng/ml), while 2 patients (1.0%) had a low C-peptide (<1.0 ng/ml). Multivariate analysis confirmed that waist circumference, triglycerides, and HbA1c were the independent predictors for the elevation of C-peptide. It was observed that the mean C-peptide levels decreased to 1.7 ± 0.9 ng/ml 1 year after bariatric surgery with a mean reduction of 64.1%. One year after surgery, 160 patients (78.0%) out of a total of 205 patients had a remission of their T2DM. Patients in the bypass group had a higher diabetes remission rate (91.2%; 134 out of 147) in comparison to patients in the restrictive group (44.8%; 26 out of 58, p < 0.001). The diabetes remission rates for those with preoperative C-peptide <3, 3-6, and > 6 ng/ml were 26 out of 47 (55.3%), 87 out of 108 (82.0%), and 47 out of 52 (90.3%), p < 0.001, respectively.
Baseline C-peptide is commonly elevated in morbidly obese patients with T2DM. There was a marked reduction in C-peptide after a significant weight reduction 1 year after surgery with a T2DM remission rate of 78.0%. Thus, bariatric surgery is recommended for obesity-related T2DM patients with elevated C-peptide.
Obesity Surgery 12/2011; 22(2):293-8. · 3.29 Impact Factor