胃旁路术对糖尿病大鼠糖脂代谢的影响

目的 观察Roux-en-Y胃旁路术对糖尿病Coto-Kakizaki(CK)大鼠糖脂代谢的影响.方法 18只GK大鼠随机等分为Roux-en-Y胃旁路手术组(RYGB组)、假RYGB组和对照组;观察手术后1、2、4、12周各组大鼠空腹血糖、C肽和体质量增加值变化,同时观察手术后4周、12周血浆糖化血红蛋白、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇含量变化.结果 手术前3组大鼠各检测指标差异无统计学意义(P>0.05).手术后1、2、4、12周RYGB组大鼠空腹血糖(7.0±0.8比6.5±1.0比6.3±1.5比5.6±1.7比4.3±0.5,P<0.01)明显降低,空腹C肽(0.21±0.06比0.28±0.09比0.52±0.06比0.71±0.06比0.78±0.06,P<0.01)显著升高;手术后4、12周大鼠糖化血红蛋白(9.71±1.34比9.09±1.21比7.34±1.17,P<0.01)、甘油三酯(1.32±0.17比0.87±0.05比1.22±0.15,P<0.01)、低密度脂蛋白胆固醇(1.61±0.25比1.21±0.20比1.16±0.15,P<0.01)明显降低,高密度脂蛋白胆同醇(0.83±0.10比1.11±0.12比1.23±0.16,P<0.01)明显升高(P<0.01).各组大鼠体质量增加值差异均有统计学意义(P<0.05).假RYGB组和对照组其余各检测指标的变化差异均无统计学意义(P>0.05).结论 Roux-en-Y胃旁路术可改善非肥胖糖尿病GK大鼠血糖和血脂代谢,且与体质量变化无关.     

胃旁路术对糖尿病大鼠糖脂代谢的影响

Objective To observe the effects of gastric bypass on carbohydrate and lipid metabolism in Goto-Kakizaki (GK) type 2 diabetic rats. Methods Eighteen male GK rats were randomly divided into Roux-en-Y gastric bypass (RYGB) group, sham RYGB group (sham-RYGB) and pair-fed control group. Before and 1, 2, 4, 12 weeks after operation, the values of fasting glucose (FPG), weight gain and C-peptide (FC-P) were measured, and levels of glycosylated hemoglobin (GHbAlc) , triglycerides (TG) , high density lipoprotein (HDL-c) and low density lipoprotein (LDL-c) were determined before and 4, 12 weeks after operation. Results No significant differences were observed in pre-operative values (P>0. 05) among three groups. In RYGR group, serum levels measured before and 1, 2, 4, and 12 weeks after operation were as follows:FPG (7.0±0. 8 vs. 6. 5 ±1.0 vs. 6. 3±1. 5 vs. 5. 6±1. 7 vs. 4. 3±0.5, P<0.01), FC-P(0.21±0.06 vs. 0.28±0.09 vs. 0. 52±0. 06 vs. 0.71±0.06 vs. 0.78±0.06,P<0. 01) ;levels of GHbAlc (9. 71±1. 34 vs. 9. 09±1. 21 vs. 7. 34±1. 17,P<0. 01 ) , TG (1.32±0.17 vs. 0.87±0.05 vs. 1. 22±0.15,P <0.01), and LDL-c (1.61 ±0.25 vs. 1.21 ±0.20 vs. 1. 16 ±0.15,P<0.01), HDL-c (0.83 ±0.10 vs. 1.11 ±0.12 vs. 1.23 ±0. 16,P<0.01) before and 4, 12 weeks after operation. Weight gains had significant difference in each group before and after operation.In sham-RYGB and control groups, no significant differences were observed before and after operation in values of the other parameters. Conclusion Roux-en-Y gastric bypass can significantly regulate the metabolism of carbohydrate and lipid in GK rats, and the effects are not associated with weight gain.     

腹腔镜胃旁路术后患者血浆胆汁酸的变化及其对糖脂代谢的影响

目的:探讨腹腔镜胃旁路术后血浆胆汁酸浓度的变化及其对血脂、血糖的影响。方法:选择41例行腹腔镜胃旁路术的2型糖尿病合并肥胖患者作为研究对象,对比分析术前及术后1年BMI、糖脂代谢参数、血浆胆汁酸浓度。结果:与术前相比,术后BMI、糖脂代谢参数、血浆胆汁酸浓度有显著改变。相关性分析得出,术后胆汁酸的变化与糖脂代谢参数的变化显著相关。结论:腹腔镜胃旁路术后患者糖脂代谢的改善可能与血浆胆汁酸浓度升高有关。     

Roux-en-Y胃旁路术对糖尿病大鼠肾脏的保护作用

目的 观察Roux-en-Y胃旁路术对糖尿病Goto-Kakizaki (GK)大鼠肾脏的保护作用.方法 18只GK大鼠随机等分为Roux-en-Y胃旁路手术组(RYGP组)、假RYGP组和对照组;观察手术前、手术后12周各组大鼠血清血栓素(TXB2)、6-酮-前列环素(6-kET-1o-PGF1a)、内皮素-1( ET-1)、尿素氮(sCr)、肌酐(BUN)和24h尿蛋白(24 h uPro)含量;手术后12周苏木素-伊红(HE)染色观察大鼠肾脏病理变化.结果 手术前3组大鼠各检测指标差异无统计学意义(P＞0.05).与手术前比较,手术后12周,假RYGP组大鼠TXB2(66.31±6.13) ng/L比(101.42 ±9.70) ng/L、ET-1 (58.31±5.32) ng/L比(79.01±6.89) ng/L、sCr( 48.78±3.66) μmol/L比(70.33±6.21)μmol/L、BUN(5.41±0.68) mmol/L比(8.35±0.92) mmol/L和24h uPro (0.44±0.10) g/24 h比(0.86 ±0.17) g/24 h均显著升高,6-kET-1o-PGF1a(85.72±6.87) ng/L比(60.41±8.23) ng/L显著降低,差异均有统计学意义(P＜0.05);对照组与假RYGP组一样获得相似的结果;RYGP组大鼠各检测指标变化差异无统计学意义(P＞0.05).手术后12周,RYGP组与假RYGP组比较TXB2(72.31±7.56) ng/L比(101.42±9.70)ng/L、ET-1 (62.11±6.26) ng/L比(79.01 ±6.89)ng/L、sCr (54.36±4.12)μmol/L比(70.33±6.21)μmol/L、BUN( 5.71±0.86) mmol/L比(8.35±0.92) mmoL/L、24 h uPro(0.52 ±0.10) g/24 h比(0.86±0.17)g/24 h和6-kET-1o-PGF1a( 83.22±5.62) ng/L比(60.41±8.23) ng/L差异均有统计学意义(P＜0.05);RYGP组与对照组比较,各检测指标差异均有统计学意义(P＜0.05);假RYGP组、对照组血清TXB2与6-kET-1o-PGF1a呈显著负相关,与ET-1呈显著正相关(P＜0.05).手术后12周,假RYGP组和对照组大鼠肾脏有明显病理性损害;RYGP组大鼠肾脏病理变化不明显.结论 Roux-en-Y胃旁路术对GK大鼠肾脏具有保护作用.     

胃旁路术对非肥胖型2型糖尿病大鼠糖代谢的影响

目的:观察胃旁路术对非肥胖型2型糖尿病大鼠(GK大鼠)糖代谢的影响.方法:GK大鼠20只,Wistar大鼠10只,随机分为GK手术组、GK假手术组和Wistar假手术组,每组10只;手术组行胃旁路术;测定术前1周及术后第1、2、4、8、12周各组体质量、空腹血糖(FPG)、糖化血红蛋白(HbA1c)水平和血清胰岛素(INS)含量.结果:术后12周,GK手术组大鼠体质量由术前的(255.10±21.09)g上升到(364.55±25.73)g,FPG和HbA1c分别由术前的(11.36±1.14)mmol/L和(8.91±0.36)%下降到(8.36±0.62)mmol/L和(6.35±0.46)%,而血清INS由术前(32.76±2.37)μIU/mL上升到(55.14±5.45)μIU/mL.结论:胃旁路术可以明显降低GK大鼠的空腹血糖,改善糖代谢障碍.     

Roux-en-Y胃旁路术对糖尿病大鼠行为及能量代谢的影响

目的:探讨RYGB对2型糖尿病大鼠行为模式、生理应激、能量代谢的影响.方法:将2型糖尿病的GK大鼠模型随机分为两组,RYGB组(行RYGB,n=5)与Sham组(行假手术,n=5),另外将年龄匹配的正常Wistar大鼠作为正常对照组(对照组,n=5).分别于术前及术后2周、4周测量体重、空腹血糖.术后3周应用大鼠代谢监...     

胃旁路术对糖尿病肾病蛋白尿影响的随访研究

目的 :探讨胃旁路术对糖尿病肾病(diabetic nephropathy,DN)的疗效。方法 :回顾性分析58例接受胃旁路术的肥胖合并DNⅢ/Ⅳ期病人,随访1年分析手术对2型糖尿病、血压、肾功能以及蛋白尿的影响。结果:术后1年降糖及降压药物用量显著减少,体重、血糖、糖化血红蛋白以及胰岛素抵抗指标均显著下降,DNⅢ期和Ⅳ期糖尿病缓解率分别为83.9%和77.8%。手术前、后肾功能无显著变化,24 h尿蛋白(正常值为0.05]。结论:胃旁路术对2型糖尿病合并肥胖有显著减重、降糖的疗效,且有缓解DN进展的可能。     

Roux-en-Y胃旁路术对2型糖尿病大鼠肝脏糖异生的影响

目的探讨Roux-en-Y胃旁路术对2型糖尿病大鼠肝脏糖异生的影响及意义。方法将40只GotoKakizaki（GK）大鼠按随机数字表法分为Rollx-en-Y胃旁路术组（A组,20只）和假手术组（B组,20只）。分别于术前及术后1、2、4周行口服葡萄糖耐量实验（OGYr）。并记录体质量。于术前及术后第4周测定两组大鼠糖化血红蛋白（HbAlc）水平。术后第4周处死大鼠获取肝脏组织,采用反转录聚合酶链反应和Westernblot技术检测肝脏组织葡萄糖6磷酸酶（G-6-P）、磷酸烯醇式丙酮酸激酶（PEPCK）的mRNA及蛋白相对表达量。结果术后1、2、4周,A组大鼠平均空腹血糖分别为6．5、4．9和4．7mmol／L,而B组分别为10-3、10．4和12．5mmol／L。两组比较差异均有统计学意义（均P〈0．05）;A组灌胃后2h血糖分别平均为8．3、6．4和5．5mmol／L,B组为21．4、23．8和24．7mmol／L,两组比较差异均有统计学意义（均P〈0．05）。A组术后第4周HbAlc为（6．8±1．0）％,低于B组的（7．9±0．8）％（P〈0．05）。A组术后4周肝脏G-6-P和PEPCK的mRNA相对表达较B组分别降低了21．0％和25．9％,蛋白表达水平也相应降低（均P〈0．05）。PAS染色示肝脏糖原沉积明显增多。结论Roux-en-Y胃旁路术后肝脏糖异生关键酶的mRNA相对表达和蛋白含量明显降低。肝脏糖异生减少．这可能是该术式的降糖机制之一。     

正确认识胃旁路术后并发症

Roux-en-Y胃旁路术（RYGBP）和可调节性胃囊带术（AGB）是目前最为流行的减肥术式,其确切疗效已在世界范围内得到公认,但从减肥及降糖效果、术后患者的满意程度、长期并发症来看,RYGBP优于AGB。然而由于手术操作的复杂性、胃肠道解剖结构的改变,术后难免会出现一系列手术潜在的并发症及营养缺乏,如果不采取积极的治疗措施,将会引起严重的、甚至不可逆的损害。因而充分认识RYGBP这一手术方式的潜在并发症及营养缺乏情况,对于预防、诊断及治疗有着重要意义。     

胃旁路术对糖尿病大鼠胰岛β细胞凋亡的影响及其机制研究

目的 研究胃旁路手术对非肥胖2型糖尿病大鼠胰岛β细胞凋亡的影响及其机制.方法 将72只8周龄的GK大鼠随机分为手术组(O组,18只)、假手术组(S组,18只)、饮食控制组(F组,18只)和对照组(C组,18只),术前和术后1、2、4、8周检测比较空腹、餐后血糖、胰岛素和胰高血糖素样肽-1(GLP-1)水平.术后2、4、8周取血测餐后血糖后,分批随机处死大鼠,每批每组处死6只,大鼠处死后分离胰腺并取出待用.原位末端标记法检测胰岛β细胞凋亡;免疫组化方法检测凋亡相关蛋白Bcl-2、Bax的表达.结果 O组术后第4周空腹血糖由术前的(16.2 ±0.8)mmol/L下降到(9.2±0.6)mmol/L,术后第8周血糖为(9.7±0.7)mmoL/L;术后第4周餐后血糖由术前的(31.1±1.1)mmoi/L降至(13.1±0.7)mmol/L,术后第8周为(12.3 ±0.7)mmol/L;术后第4周空腹血清胰岛素水平由术前的(28.0±1.2)mU/L升至(62.8±1.9)mU/L,术后第8周为(61.7±1.4)mU/L,术后第4、8周餐后血清胰岛素水平分别为(77.4±1.1)mU/L、(77.1±1.0)mU/L;术后第2周空腹GLP-1由术前的(10.7±1.0)pmol/L升至(13.5±0.8)pmol/L,至术后第4、8周分别为(26.1±0.9)pmol/L、(25.3±1.2)pmol/L;O组各测量值术后各时相点与术前比较差异均有统计学意义(P＜0.05),与其他组比较差异亦有统计学意义(P＜0.05).O组大鼠胰岛细胞凋亡率术后4周下降至(5.9 ±0.7)%,术后8周凋亡率为(6.3±1.1)%,差异有统计学意义(P＜0.05).O组Bcl-2蛋白表达术后2、4、8周表达量分别为31.3±1.5、35.7±1.0和35.8 ±0.8,明显高于同时间点的其他3组,差异有统计学意义(P＜0.05);Bax蛋白术后2、4、8周表达量分别为13.3±0.9、10.8 ±0.9和10.9±1.1,明显低于相同时间点的其他3组,差异有统计学意义(P＜0.05).结论 胃旁路手术可显著降低糖尿病大鼠血糖,促进GLP-1分泌,从而调节Bcl-2通路,显著抑制胰岛β细胞凋亡,保护胰岛B细胞.     

Roux-en-Y胃肠道重建改善非肥胖性糖尿病胃癌患者的糖脂代谢

目的 观察Roux-en-Y胃肠道重建对非肥胖件糖尿病胃癌患者血糖和血脂代谢的影响.方法 非肥胖性糖尿病胃癌患者57例行根治性远端胃切除术,其中35例行Roux-en-Y胃肠道重建,22例行Billroth Ⅰ式胃肠道重建.观察手术前、手术后3个月和6个月两组体质量指数、糖化血红蛋白、空腹血糖、胰岛素、C肽、甘油三酯、总胆固醇、高密度脂蛋白和低密度脂蛋白含量的变化,并检测口服葡萄糖后2 h血糖、胰岛素和C肽的变化.结果 手术前两组各检测指标之间相比差异均无统计学意义(P＞0.05).手术后两组体质量指数变化之间相比差异无统计学意义(P＞0.05);术前、手术后3个月和6个月Roux-en-Y胃肠道重建组空腹血糖为(9.3±0.9)mmol/L比(7.2±2.1)mmoL/L比(7.1±0.8)mmoL/L,P=0.000;糖化血红蛋白为(9.2±1.2)%比(7.3±1.2)%比(7.2±1.1)%,P=0.000;空腹甘油三酯为(3.21±0.88)mmoL/L比(2.12±0.97)mmol/L比(2.02±0.09)mmol/L,P=0.000;空腹总胆固醇为(6.4±1.9)mmol/L比(4.3±1.0)mmol/L比(4.1±1.0)mmol/L,P=0.000;空腹低密度脂蛋白为(3,61±1.05)mmol/L比(2.77±0.68)mmol/L比(2.71±0.18)mmol/L,P=0.000;2 h血糖为(17.6±2.5)mmoL/L比(12.1±1.9)mmoL/L比(11.6±2.3)mmol/L,P=0.000,含量较手术前明显下降(P＜0.01).空腹胰岛素为(98±11)pmol/L比(120±9)pmoL/L比(122±8)pmol/L,P=0.000;空腹C肽为(0.21±0.08)mmol/L比(0.30±0.01)mmol/L比(0.30±0.01)mmol/L,P=0.000;空腹高密度脂蛋白为(1.08±0.10)mmol/L比(1.61±0.34)mmol/L比(1.62±0.09)mmol/L,P=0.000;2 h胰岛素为(410±19)pmol/L比(446±19)pmol/L比(459±18)pmol/L,P=0.000;2 h C肽为(0.87±0.17)mmol/L比(1.22±0.14)mmol/L比(1.19±0.15)mmol/L,P=0.000.Billroth Ⅰ式胃肠道重建组糖化血红蛋白为(9.2±1.2)%比(8.4±1.6)%比(8.3±1.1)%,P=0.046.结论 Roux-en-Y胃肠道重建术可改善非肥胖性糖尿病胃癌患者血糖和血脂代谢,且与体质量指数变化无关.     

胃转流术对GK大鼠肝脏脂代谢的影响及其意义

目的:探讨胃转流术对自发性糖尿病Goto-Kakizaki(GK)大鼠肝脏脂代谢的影响及其意义。方法:40只雄性GK大鼠随机均分为实验组与对照组。实验组行Roux-en-Y胃转流术,对照组行胃窦十二指肠离断原位吻合术。分别于术前、术后1,2,4周检测两组大鼠空腹血糖、口服葡萄糖耐量试验2 h(OGTT 2 h)的血糖;并于术前及术后4周测定大鼠血液中空腹游离脂肪酸(FFA),胆固醇(Tch),甘油三酯(TG)。此外,于术中及术后第4周获取大鼠肝脏组织行免疫组化油红O染色,观察肝脏TG沉积情况。结果:与术前比较,实验组大鼠术后空腹及OGTT 2 h血糖值均呈下降趋势,两者在术后2,4周时明显降低(均P<0.05);术后第4周,实验组大鼠血液中FFA明显降低(P<0.05),而TG及Tch无明显变化(均P>0.05),肝脏组织切片内TG沉积现象明显减少。对照组以上所有指标手术前后均无明显改变(均P>0.05)。结论:胃转流术降低GK大鼠血糖的机制可能与改善肝脏脂质代谢,降低FFA含量,使胰岛素抵抗得以缓解有关。     

Effects of pulsatile cardiopulmonary bypass on carbohydrate and lipid metabolism

The influence of pulsatile perfusion on carbohydrate and lipid metabolism was examined in 40 patients (20 pulsatile and 20 non-pulsatile) who underwent open-heart surgery. The pulsatile assist device was used for pulsatile cardiopulmonary bypass during aortic cross-clamping only, and samples of the mixed venous blood were taken every 20 minutes. There were no statistically significant differences between pulsatile and non-pulsatile groups with respect to plasma levels of glucose, insulin, glucagon, free fatty acids and ketone bodies. However, an increase in the plasma level of noradrenaline was significantly suppressed in the pulsatile group, and triglyceride levels were significantly higher in the pulsatile than in the non-pulsatile group. These data suggest that pulsatile flow attenuates the catecholamine stress response to cardiopulmonary bypass and has a protective effect on liver function during bypass.     

Effects of Roux-en-Y gastric bypass and ileal transposition surgeries on glucose and lipid metabolism in skeletal muscle and liver

BackgroundRoux-en Y gastric bypass (RYGB) and ileal transposition (IT) surgeries produce weight loss and improve diabetic control; however, the mechanisms of glycemic improvements are largely unknown. Because skeletal muscle and liver play a key role in glucose homeostasis, we compared the effects of RYGB and IT surgeries on key molecules of glucose and lipid metabolism in muscle and liver.MethodsSprague-Dawley rats were subjected to RYGB, IT, or sham surgeries; sham-animals were ad-lib fed or pair-fed to RYGB rats (n = 7-9/group). At 8 weeks postoperatively, blood samples were collected for glucagon-like peptide-1 (GLP-1) and insulin analyses by ELISA. Leg muscle and liver tissues were analyzed for mRNA (RT-qPCR) and/or protein abundance (immuno blotting) of important molecules of glucose and lipid metabolism [glucose transporter-4 (GLUT-4), hexokinase, phosphofructokinase (PFK), adenosine monophosphate activated protein kinase-α (AMPKα), cytochrome C oxidase-IV (COX-IV), citrate synthase, carnitine palmitoyl transferase-1 (CPT-1), medium-chain acyl-CoA dehydrogenase (MCAD), peroxisome proliferator-activated receptor gamma co-activator 1 α (PGC-1 α), PGC-1-related coactivator (PRC), uncoupling protein-3 (UCP-3)].ResultsPlasma GLP-1 concentrations were increased comparably with RYGB and IT. RYGB and IT increased muscle GLUT-4 protein content, muscle hexokinase mRNA, and liver PFK mRNA. IT increased muscle AMPKα and COX-IV protein content and liver citrate synthase activity. IT increased muscle CPT-1, MCAD and PRC mRNA, whereas RYGB increased UCP-3 mRNA in muscle and liver, and PGC-1 α mRNA in liver.ConclusionThe data suggest that RYGB and IT surgeries lead to enhanced GLP-1 secretion and produce similar stimulatory effects on important molecules of glucose metabolism but differential effects on key molecules of lipid oxidation in muscle and liver.     

硫化氢对2型糖尿病大鼠胰岛素抵抗和脂代谢的影响

目的 观察硫化氢对2型糖尿病(T2DM)大鼠胰岛素抵抗和脂代谢的影响.方法 65只大鼠采用高糖高脂饮食+腹腔注射链脲佐菌素(STZ)的方法建立T2DM模型,将45只成模大鼠随机分为糖尿病(DM)、DM+硫氢化钠(NaHS)和DM+ DL-炔丙基甘氨酸(PAG)组,每组各15只,另设正常对照组.DM+ NaHS组大鼠腹腔注射NaHS[56 μmol/(kg·d)],DM+ PAG组腹腔注射PAG[50 mg/(kg·d)],对照组和DM组给予相同体积的生理盐水,连续给药2周.给药结束后,测定大鼠空腹血糖(FBG)、胰岛素(FIns)、甘油三酯(TG)、总胆固醇(TC)、游离脂肪酸(FFA),计算胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI);测定胰腺组织中硫化氢(H2S)浓度,免疫组织化学方法检测胰腺组织胰岛素表达.结果 与对照组比较,DM组大鼠FBG[(18.22±3.99) mmol/L]、TG[(1.54 ±0.16) mmol/L]、TC[(3.27±0.38) mmol/L]、FFA[(504.68±37.70) μmol/L]水平及HOMA-IR升高(P＜0.05),FIns[(41.79±3.43) mU/L]和ISI(-6.57 ±0.37)降低,胰腺组织H2S浓度[(96.98±19.44) μmol/L]升高,胰腺组织胰岛素阳性表达细胞面积(AIEP)和胰岛素阳性染色率(PRSI)降低,差异均有统计学意义(P＜0.05);与糖尿病组比较,NaHS干预后,糖尿病大鼠FBG[(25.42 ±0.21) mmol/L]、TG[(2.40 ±0.21) mmol/L]、TC[(4.80 ±0.16) mmol/L]、FFA[(633.96±25.64)μmol/L]水平及HOMA-IR升高更明显,FIns[(29.36±2.65) mU/L]和ISI(-6.58±0.27)降低,胰腺组织H2S浓度[(134.50±12.70)μmol/L]明显升高,AIEP和PRSI降低,差异均有统计学意义(P＜0.05);应用PAG后,糖尿病大鼠血浆FBG[(10.83±1.10) mmol/L]、TG[(1.30±0.12) mmol/L]、TC[(2.79 ±0.33) mmol/L]、FFA[(383.39±69.00) μmol/L]水平明显降低,胰岛素抵抗改善,FIns[(51.58±1.49) mU/L]和ISI(-6.32±0.11)明显升高,胰腺组织H2S浓度[(71.48±10.94) μmol/L]明显降低,AIEP和PRSI增加.结论 H2S通过影响T2DM大鼠胰岛素抵抗和脂代谢参与糖尿病发生发展.     

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.     

Roux-en-Y胃旁路术改善非肥胖性2型糖尿病患者的糖脂代谢

目的 观察Roux-en-Y胃旁路术对非肥胖性2型糖尿病患者血糖和血脂代谢的影响.方法 共37例非肥胖2型糖尿病患者接受Roux-en-Y胃旁路术,观察其手术前、手术后3个月和6个月的体质量指数、糖化血红蛋白、空腹血糖、胰岛素、C肽、胰岛素抵抗指数、甘油三酯、总胆固醇、高密度脂蛋白和低密度脂蛋白含量的变化,并比较口服葡萄糖后2 h血糖、胰岛素和C肽的变化.结果 本组37例患者无严重围手术期并发症.手术前、手术后3个月和6个月体质量指数变化之间相比差异均无统计学意义(P>0.05);手术前、手术后3个月和6个月空腹血糖[(8.8±0.9)mmol/L、(7.0±2.0)mmol/L、(6.3±0.6)mmol/L,P<0.01]、糖化血红蛋白[(8.2%±1.2%、7.0%±0.8%、6.2%±0.7%,P<0.01]、空腹胰岛素[(10.6±1.2)mU/L、(9.0±0.9)mU/L、(9.0±0.8)mU/L,P<0.05]、空腹C肽[(1.9±0.5)nmol/L、(1.2±0.6)nmol/L、(1.2±0.4)nmol/L,P<0.01]、空腹甘油三酯[(3.3±0.8)mmol/L、(2.7 ±0.9)mmol/L、(2.6±0.7)mmol/L,P<0.05]、空腹总胆固醇[(6.5±1.8)mmol/L、(4.6±0.9)mmol/L、(4.2±1.0)mmol/L,P<0.05]、空腹低密度脂蛋白[(3.6±1.2)mmol/L、(2.8±0.8)mmol/L、(2.7±0.2)mmol/L,P<0.01]、餐后2 h血糖[(18.6±3.0)mmol/L、(12.7±2.3)mmol/L、(11.4±2.0)mmol/L,P<0.01]、胰岛素抵抗指数[(3.2±1.7)、(2.6±1.6)、(2.5±1.3),P<0.05]之间相比差异均有统计学意义.空腹高密度脂蛋白[(1.2±0.1)mmol/L、(1.4±0.4)mmol/L、(1.4±0.2)mmol/L,P<0.01]、餐后2 h胰岛素[(17.2±3,4)mU/L、(26.3±4.7)mU/L、(28.6±4.1)mU/L,P<0.01]、2 h C肽[(4.2±1.0)nmol/L、(6.3±1.5)nmol/L、(6.2±1.4)nmol/L,P<0.01]在手术后均明显升高.结论 Roux-en-Y胃旁路术可改善非肥胖性2型糖尿病患者血糖和血脂代谢,且与体质量指数变化无关.

Abstract：

Objective To evaluate Roux-en-Y gastric bypass operation on carbohydrate and lipid metabolism in type 2 diabetes mellitus patients with BMI range of 24 -29. Methods Thirty seven cases of type 2 diabetes mellitus patients undergoing Roux-en-Y gastric bypass operation were studied. Body mass index (BMI), glycosylated hemoglobin ( GHbAlc), fasting glucose ( FPG), fasting insulin (FIns) and C-peptide( FC-p), HOMA-IR, oral glucose tolerance (OGTT) including 2 hour insulin (2hIns) and C-peptide (2hC-p) , plasma levels of total cholesterol (TC), triglycerides(TG), high density lipoprotein( HDL-c)and low density lipoprotein ( LDL-c) were measured preoperatively and on 3 months, 6 months, later postoperatively. Result There was no statistically significant difference between BMI values measured preoperatively and postoperatively (P>0. 05 ). Serum levels measured in pre-operative and third and sixth post-operative months were: FPG (8. 8 ± 0. 9, 7. 0 ± 2. 0, 6. 3 ± 0. 6, P<0. 01) ( mmol/L) , GHbAlc (8.2±1.2, 7.0±0.8, 6.2±0.7, P<0.01)(%), FIns(10. 6 ±1. 2, 9.0±0.9, 9.0±0.8, P<0.05)(mU/L), FC-p(1.9±0.5, 1.2 ±0.6, 1.2 ±0.4, P<0. 01) (nmol/L), TG(3.3 ±0.8, 2.7 ±0.9,2.6±0.7, P<0.05)(mmol/L), TC(6.5±1.8, 4.6±0.9, 4.2 + 1.0, P<0. 05) (mmol/L)and LDL-c (3. 6 ±1.2, 2. 8 ±0.8, 2. 7 ±0.2, P<0.01) (mmol/L), 2 hour glucose after OGTT(2hPG) (18. 6 ±3.0, 12.7 ±2.3, 11.4±2.0, P<0. 01) (mmol/L), HOMA-IR(3. 2 ± 1. 7, 2.6±1.6, 2. 5 ±1.3, P<0. 05). Postoperative levels of HDL-c (1. 2 ± 0. 1, 1. 4 ± 0. 4, 1. 4 ± 0. 2, P<0. 01) ( mmol/L) , 2hIns (17. 2 ±3.4, 26. 3 ±4.7, 28. 6 ±4.1, P<0. 01) (mU/L)and 2hC-p(4. 2 ± 1. 0, 6. 3 ± 1. 5, 6. 2 ± 1.4,P<0. 01 ) ( nmol/L) were significantly higher than that of the pre-operative values ( P<0. 01 ).Conclusions Roux-en-Y gastric bypass significantly improves the metabolism of carbohydrate and lipid in type 2 diabetes patients with BMI 24-29, and the effects are not associated with weight loss.