腹腔镜下胃旁路术治疗2型糖尿病

目的：探讨腹腔镜下胃旁路手术治疗2型糖尿病的有效性及可行性。方法参照2011年中国《手术治疗糖尿病专家共识》,选择2型糖尿病患者实施胃旁路手术,并回顾性分析其中随访满12个月的52例患者的糖代谢指标、胰岛细胞功能指标。结果本组2型糖尿病患者术后治疗有效45例（86.5%）,完全缓解38例（73.1%）,部分缓解7例（13.5%）,无效7例（13.5%）。术后空腹血糖、餐后2 h 血糖、糖化血红蛋白较术前明显下降（P〈0.05）;胰岛素与术前比较有统计学差异,但是 C 肽无统计学意义。虽然术后有一定的手术相关并发症,但总体可控。结论腹腔镜下胃旁路手术是2型糖尿病患者一种有效可行的治疗方法,但需严格把握手术指征;术后胰岛素敏感性的提高发挥重要的治疗作用。     

胃转流术对2型糖尿病大鼠的降糖作用及对糖耐量和胰岛素抵抗的影响

目的 观察胃转流术(CBP)对2型糖尿病大鼠的降糖效果及对糖耐量和胰岛素抵抗的影响.方法 将健康雄性SD大鼠随机分为正常组(NO组,n=10)和造模组(n=32).成模大鼠随机分为糖尿病手术组(DO组)、假手术组(DS组)和对照组(DC组),每组8只.检测手术前后各组空腹血糖、胰岛素、口服葡萄糖30min后的血糖及胰岛素抵抗指数(HOMA-IR).检测DO组术前与术后第4周口服葡萄糖耐量实验后0、10、30、60、120、180 min血糖,计算糖耐量曲线下面积.结果DO组GBP术后第8周空腹血糖由术前的(17.80±2.26)mmol/L下降到(6.18±0.53)mmol/L(P<0.05),NO组手术前后空腹血糖无明显变化.口服葡萄糖30 min后血糖DO组下降更为明显,由术前的(29.20±1.46)mmol/L至术后第8周下降到(13.55±0.86)mmol/L(P<0.05).术后4周DO组各时间点OGTT曲线下面积(AUC)下降约40.1%.DO组术后8周HOMA-IR明显下降,由术前的9.36±0.90下降至4.03±0.34(P<0.05).结论 胃转流术能明显降低2型糖尿病大鼠的血糖水平,且能明显改善糖耐量和胰岛素抵抗,并对正常血糖值无影响.     

Improvement in insulin resistance after gastric bypass surgery is correlated with a decline in plasma 2-hydroxybutyric acid

Background

Gastric bypass surgery for weight reduction often corrects dysglycemia in diabetic patients, but a full understanding of the underlying biochemical pathways continues to be investigated.

2型糖尿病患者胃转流术后游离脂肪酸的改变及其意义

目的探讨2型糖尿病(T2DM)患者行胃转流术后血清游离脂肪酸(FFA)的变化及意义。方法检测20例T2DM患者于手术前及手术后3个月和6个月时的血浆FFA,胰岛素抵抗指数(HOMA-IR)空腹血糖(FPG),餐后2小时血糖(PPG),糖化血红蛋白(HbA1C),体质量指数(BMI)等指标,并以20例健康人群做对照。结果 T2DM组15例完全缓解,3例部分缓解,2例无效。T2DM组术前FFA,HOMA-IR,FPG,PPG,HbA1C均显著高于健康对照组。T2DM组术后3~6个月FFA,HOMA-IR呈进行性下降,均显著低于术前(均P<0.01)。FPG,PPG,HbA1C,BMI亦明显低于术前(均P<0.01)。T2DM组FFA与HOMA-IR在术前,术后3,6个月的相关系数分别为0.58(P<0.01),0.46(P<0.05),0.48(P<0.05)。结论胃转流术能降低T2DM患者血清FFA,并由此减轻患者胰岛素抵抗,这可能是胃转流术治疗T2DM的作用机制之一。     

Changes in postprandial gut hormones after metabolic surgery: a comparison of gastric bypass and sleeve gastrectomy

Background

Laparoscopic gastric bypass (GB) is reportedly more effective than laparoscopic sleeve gastrectomy (SG) in the treatment of patients with a low body mass index and type 2 diabetes mellitus. However, the mechanism remains speculative. We compared the postprandial gut hormone patterns between patients undergoing laparoscopic GB and laparoscopic SG at 2 years after surgery in a hospital-based, prospective study.

Methods

A total of 16 laparoscopic GB and 16 laparoscopic SG patients were followed up and appraised for glucose homeostasis. Two years after surgery, the mixed meal test and gut hormones were evaluated in 13 laparoscopic GB and 13 laparoscopic SG patients who had been included in the previous randomized trial.

Results

The preoperative characteristics, such as body mass index, body weight, waist circumference, and duration of T2DM were comparable between the 2 groups. T2DM remission was achieved in 13 (81%) laparoscopic GB and 3 (19%) laparoscopic SG patients (P < .05) 2 years after surgery. The laparoscopic GB patients had lost more weight and had a smaller waist circumference and lower levels of glucose and hemoglobin A1c, and lower insulin resistance than the SG patients. Significant differences were found in acyl ghrelin, des-acyl ghrelin, cholecystokinin, and resistin between the 2 groups, but none in obestatin, gastric inhibitory peptide, glucagon-like peptide-1, and leptin.

Conclusions

Both laparoscopic GB and laparoscopic SG have strong hindgut effects after surgery, but GB has a significant duodenal exclusion effect on cholecystokinin. The laparoscopic SG group had lower acyl ghrelin and des-acyl ghrelin levels but greater concentrations of resistin than the laparoscopic GB group.     

Gastrointestinal manifestations after Roux-en-Y gastric bypass surgery in individuals with and without type 2 diabetes

BackgroundRoux-en-Y gastric bypass (RYGB) surgery is an effective treatment for obesity, which improves cardiovascular health and reduces the risk of premature mortality. However, some reports have suggested that RYGB may predispose patients to adverse health outcomes, such as inflammatory bowel disease (IBD) and colorectal cancer.ObjectivesThe present prospective study aimed to evaluate the impact of RYGB surgery on cardiovascular risk factors and gastrointestinal inflammation in individuals with and without type 2 diabetes (T2D).SettingUniversity hospital setting in Finland.MethodsBlood and fecal samples were collected at baseline and 6 months after surgery from 30 individuals, of which 16 had T2D and 14 were nondiabetics. There were also single study visits for 6 healthy reference patients. Changes in cardiovascular risk factors, serum cholesterol, and triglycerides were investigated before and after surgery. Fecal samples were analyzed for calprotectin, anti-Saccharomyces cerevisiae immunoglobulin A antibodies (ASCA), active lipopolysaccharide (LPS) concentration, short-chain fatty acids (SCFAs), intestinal alkaline phosphatase activity, and methylglyoxal-hydro-imidazolone (MG-H1) protein adducts formation.ResultsAfter RYGB, weight decreased on average ?21.6% (?27.2 ± 7.8 kg), excess weight loss averaged 51%, and there were improvements in cardiovascular risk factors. Fecal calprotectin levels (P < .001), active LPS concentration (P < .002), ASCA (P < .02), and MG-H1 (P < .02) values increased significantly, whereas fecal SCFAs, especially acetate (P < .002) and butyrate (P < .03) levels, were significantly lowered.ConclusionThe intestinal homeostasis is altered after RYGB, with several fecal markers suggesting increased inflammation; however, clinical significance of the detected changes is currently uncertain. As chronic inflammation may predispose patients to adverse health effects, our findings may have relevance for the suggested association between RYGB and increased risks of incident IBD and colorectal cancer.     

Free fatty acids,glucose, and insulin in type 2 diabetes mellitus

Xu et al used the HOMA2 model to estimate the β-cell function and insulin resistance levels in an individual from simultaneously measured fasting plasma glucose and fasting plasma insulin levels. This method is based on the assumption that the glucose-insulin axis is central for the metabolic activities, which led to type 2 diabetes. However, significant downregulation of both the NKX2-1 gene and the TPD52L3 gene force an increase in the release of free fatty acids (FFAs) into the blood circulation, which leads to a marked reduction in membrane flexibility. These data favor a FFA-glucose-insulin axis. The authors are invited to extend their study with the introduction of the saturation index (number of carbon-carbon double bonds per 100 fatty-acyl chains), as observed in erythrocytes.     

胃旁路术对2型糖尿病大鼠脂肪组织胰岛素受体β及胰岛素受体底物-1表达的影响

目的：观察胃旁路术对2型糖尿病大鼠（GK大鼠）脂肪组织胰岛素受体β（IR-β）及胰岛素受体底物-1（IRS-1）表达的影响,探讨其改善胰岛素抵抗的机制。方法30只8周龄雄性GK大鼠（糖尿病模型）采用数字表法分为手术组（行胃旁路手术）、假手术组（与手术组大鼠相同部位切断后原位端端吻合）和饮食配对组（与手术组大鼠同种和同等质量的饮食）,每组10只,另10只8周龄雄性SD大鼠作为空白对照组（自由进食及饮水）。检测术前与术后4周各组大鼠空腹血糖（FPG）和空腹胰岛素（FINS）水平,计算术前及术后4周胰岛素抵抗指数（HOMA-IR）,应用蛋白印迹（Western blot）技术检测各组术后4周脂肪组织IR-β和IRS-1的表达。结果手术组术后4周FPG及 HOMA-IR 较术前明显降低（分别为5.13±0.22比11.73±0.37,2.16±0.18比5.10±0.29;均P<0.05）,并能达到空白对照组术后水平（P>0.05）;而假手术组和饮食配对组较术前无显著变化（均P＞0.05）;术后4周手术组IR-β及IRS-1表达量均明显高于其他3组（均P<0.05）。结论胃旁路术能上调2型糖尿病大鼠胰岛素信号转导通路中IR-β及IRS-1的表达,改善脂肪组织胰岛素抵抗,提高胰岛素的敏感性。     

Measures of glucose homeostasis during and after duodenal exclusion using a duodenal-jejunal bypass liner in a normoglycemic,nonobese canine model

BackgroundDiscovering the role duodenal exclusion plays in weight loss and resolution of type 2 diabetes (T2D) may help refine the surgical and nonsurgical treatment of obesity and T2D.ObjectivesTo assess changes in glucose homeostasis due to duodenal exclusion using a duodenal-jejunal bypass liner (DJBL) in a nonobese canine model.SettingAcademic laboratory setting.MethodsAn intravenous glucose tolerance test (IVGTT), and a mixed-meal tolerance test (MMTT) at baseline, 1, and 6 weeks post DJBL implantation (I1 and I6, respectively), and 1 and 6 weeks post DJBL removal (R1 and R6, respectively) were done in canines (n = 7) fed a normal chow diet.ResultsPlacement of the DJBL induced weight loss that was maintained until 4 weeks post removal (R4), despite normal food intake. Total bile acids (TBA) and glucagon-like peptide-1 (GLP-1) during the MMTT were significantly increased at I1 and were associated with increased lactate and free fatty acids. Hypoglycemia counter-regulation was blunted during the IVGTT at I1 and I6, returning to baseline at R1. While there were no changes to insulin sensitivity during the experiment, glucose tolerance was significantly increased following the removal of the DJBL at R1.ConclusionThese data show that in a normoglycemic, nonobese canine model, duodenal exclusion induces energy intake-independent weight loss and negative metabolic effects that are reversed following re-exposure of the small intestine to nutrients.     

Roux-en-Y gastric bypass increases hepatic and peripheral insulin sensitivity in rats with type 2 diabetes mellitus

BackgroundRoux-en-Y gastric bypass (RYGB) surgery for the treatment of obesity leads to long-term diabetes remission in approximately 80% of cases. The aim of this study was to investigate the effects of RYGB on hepatic and peripheral insulin sensitivity in type 2 diabetic rats and their possible mechanisms. We also tested the hypothesis that RYGB reduces lipid content and improves insulin sensitivity in hepatocytes and skeletal muscle cells.MethodsSprague–Dawley rats were divided into 4 groups: diabetic RYGB group (n = 18), diabetic RYGB sham group (n = 6), diabetic group (n = 6), and nondiabetic control group (n = 6). The hyperinsulinemic-euglycemic clamp with tracer infusion was completed at 2, 4, and 8 weeks postoperatively to assess insulin sensitivity. The lipid content in liver and muscle tissue was examined.ResultsPostoperatively, the diabetic RYGB group had significant decreases in weight, fat mass, and food intake. Two weeks after surgery, RYGB had significantly improved the hepatic insulin sensitivity index and decreased the hepatic triglyceride, total cholesterol, and fatty acyl-CoA content. The significantly increased insulin sensitivity and decreased lipid content in muscle were not detected until 4 weeks after RYGB surgery. The basal insulin and C-peptide concentrations were significantly lower than those in diabetic group by 2 weeks after RYGB.ConclusionThe increased insulin sensitivity after RYGB occurs earlier in the liver than in the muscle and both may contribute to long-term remission of type 2 diabetes. Reduced lipid content of hepatocytes and skeletal muscle cells after RYGB may contribute to the improved insulin sensitivity in these cells.     

Preoperative assessment of gut hormones does not correlate to weight loss after Roux-en-Y gastric bypass surgery

BackgroundRoux-en-Y gastric bypass (RYGB) surgery is an effective and frequently used surgical treatment for severe obesity. Postoperative weight loss varies markedly, but biomarkers to predict weight loss outcomes remain elusive. Levels of the satiety gut hormones glucagon like peptide-1 (GLP-1) and peptide YY (PYY) are attenuated in obese patients but elevated after RYGB surgery. We aimed to evaluate the preoperative responses of GLP-1 and PYY to a standard meal as a predictor of weight loss after RYGB surgery. We hypothesized that weak satiety gut hormone responses preoperatively, would predict poor weight loss after RYGB surgery.MethodsPreoperatively 43 patients (F = 25/M = 18) had GLP-1 and PYY measured in the fasting state and at 30-minute intervals over 180 minutes after a standard 400 kcal mixed meal. Weight loss was assessed at weight stability after surgery (mean 16.2 mo [CI 15.516.9]).ResultsBody mass index decreased from 44.0 kg/m² (CI 42.2–45.7) before surgery to 30.3 kg/m² (CI 28.4–32.2) after surgery (P<.001). Preoperative GLP-1 and PYY responses to food intake; as delta value between fasting and maximum as well as total responses during 180 minutes did not correlate to total weight loss (GLP-1; rho = .060 and rho = −.089, PYY; rho = −.03 and rho = −.022, respectively) or to excess weight loss % (GLP-1; rho = .051 and rho = −.064, PYY; rho = −.1 and rho = −.088, respectively).ConclusionPreoperative responses of GLP-1 and PYY to a 400 kcal mixed meal do not correlate to postoperative weight loss after RYGB surgery for morbid obesity.     

Effects of gastric bypass surgery on expression of glucose transporters and fibrotic biomarkers in kidney of diabetic fatty rats

BackgroundDiabetic nephropathy is the leading cause of chronic kidney disease. Observational studies suggest Roux-en-Y gastric bypass (RYGB) reduces progression of diabetic nephropathy.ObjectivesTo unravel the mechanisms by which RYGB is beneficial and protective for diabetic nephropathy.SettingAcademic laboratories.MethodsForty-eight Zucker diabetic fatty rats were randomized to RYGB, sham surgery (SHAM), or pair-fed (PF) groups. An oral glucose tolerance test was performed at 25 days post intervention and kidneys were harvested at 30 days. Primary outcome measures included expression of key genes and proteins in the glucose transport, oxidative stress, inflammation, and fibrosis pathways.ResultsThirty days post intervention, RYGB rats weighed 349 ± 8 g, which was lower than SHAM (436 ± 14 g, P < .001), but not PF (374 ± 18 g) rats. RYGB rats had lower fasting glucose than PF animals and improved homeostatic model assessment of insulin resistance compared with PF and SHAM groups. These enhanced metabolic outcomes were accompanied by reduced sodium-glucose co-transporter 1 (Sglt1) gene expression (−23% versus PF, P = .01) in the kidney of RYGB rats. Expression of Sglt2, Glut1, or Glut2 mRNA, or oxidative stress and inflammation markers did not differ significantly. However, RYGB surgery induced a 19% lower expression of transforming growth factor (Tgfβ) mRNA (P = .004) compared with SHAM treated animals. Notably, adenosine monophosphate-activated protein kinase phosphorylation was increased (P = .04) in kidneys of the RYGB surgery animals.ConclusionsImprovement of hyperglycemia after RYGB may reduce the glucose load on the kidney leading to a downregulation of specific glucose transporters. RYGB surgery may also attenuate kidney fibrosis through the adenosine monophosphate-activated protein kinase/TGFβ pathway.     

The effect of distal-ileal exclusion after Roux-en-Y gastric bypass on glucose tolerance and GLP-1 response in type-2 diabetes Sprague-Dawley rat model

Background

An increase in glucagon-like peptide-1 (GLP-1) mediating early diabetes remission after Roux-en-Y gastric bypass (RYGB) is believed to be associated with distal-ileal stimulation.