Objective To evaluate the effects of elevated circulating free fatty acids (FFA) level on basal and glucose stimulated insulin secretion (GSIS) of islet β-cell and to explore the pathophysiological link between FFA and impaired β-cell dysfunction. Methods Male SD rats underwent infusions with normal saline (C group), intralipid+heparin (FFA group) and N-acetylcysteine+FFA (NAC group) for 2-4 days. Insulin secretion from pancreatic tissues was evaluated during intravenous glucose tolerance test and isolated pancreas perfasion test at the end of 2 and 4 days infusion. Results After 2 days infusion, the basal insulin secretion from isolated perfused pancreas was increased in FFA group [(55.5±19.4 vs 27.4±6.7) mU/L, P<0.01], but the response to 16.7 mmol/L glucose in isolated perfased pancreas was similar in FFA and C groups. The peak value during GSIS was inhibited by 4 days FFA infusion [(46.8±33.0 vs 214.7±27.4)mIU/L,P<0.05]. GSIS was also decreased in FFA group compared with C group in IVGTr. After interfered with NAC, GSIS was partly recovered [(165.4± 14.8)mIU/L, P<0.01]. Conclusion Elevated circulating FFA levels may contribute to the abnormality of pancreatic islet β-cell through oxidative stress.

The relationship between elevated concentration of circulating free fatty acids (FFA) and insulin resistance wag studied,and the pathophysiological mechanism of insulin resistance,especially focused on oxidative stress,was explored.It was found that the elevated circulating FFA level led to insulin resistance in rats, which was partly caused by oxidative stress,and that antioxidative treatment was able to reverse the pathologic change.As a result of enhancing reactive oxygen species production[(886±105 vs 427±42)mmol/L,P<0.05] and disrupting antioxidant[(272±47 vs 561±36)μmol/L,P<0.05],elevated concentration of FFA may induce oxidative stress.

The effects of elevated levels of glucose and (or) free fatty acids on insulin secretion were studied in obese rats by intravenous glucose tolerance test and isolated pancreas perfusinn. The results showed that both glucose- and arginine-stimulated insulin secretions were severely impaired by glucolipotoxicity and the production of ketone was increased dramatically.

Objective To investigate the clinical characteristics,peripheral insulin sensitivity,and β-cell function in patients with ketosis-prone diabetes(KPD).Methods Thirty-one patients with newly diagnosed ketosisprone diabetes were admitted to West China Hospital from January 2004 to December 2009.They were divided into 2 groups according to their body mass index (BMI):OB-KPD (BMI ≥ 25 kg/m2,n =22) and Lean-KPD (BMI ＜ 23 kg/m2,n =9).10 patients with newly-onset type 2 diabetes free from ketosis (OB-DM:BMI ≥ 25 kg/m2,n =10) were enlisted as control.Detailed assessments of medical history and symptoms of hyperglycemia were performed.The islet cell antibody (ICA),insulin autoantibody (IAA),anti-glutamic acid decarboxylase antibody (GAD-Ab),fasting plasma glucose,serum insulin,C-peptide and free fat acids concentrations were measured.All of the subjects underwent oral and intravenous glucose tolerance tests,euglycemic-hyperinsulinemia and hyperglycemia clamp test,to evaluate the insulin secretion and insulin sensitivity respectively.Insulin sensitivity was determined by glucose disposal rate (GDR) of steady state during euglycemic clamp and acute insulin secretion was calculated by insulin area under curve(AUCins 0-10 min) during IVGTT.Maximal insulin secretion was determined by glucose infusion rate (GIR) and serum insulin concentration of steady state during hyperglycemic clamp test.Results Age,sex,duration of diabetes were matched among groups.A family history of diabetes was strongly associated with those patients with obesity,compared with lean ketosis prone diabetes(16/22 vs 1/9).GDR was (4.91 ± 1.82) mg · kg 1 · min-1 in subjects with OB-KPD,being lower than that in Lean-KPD patients[(6.26 ± 1.89) mg · kg 1 · min-1] and OB-DM group[(6.78-± 1.69) mg · kg 1 · min-1,P＜0.01].Serum insulin and C-peptide in OB-KPD patients were higher than Lean-KPD patients.Area under the insulin curve [AUCins0-10min (183.86 ± 31.1) mIU/L] and GIR[(2.65 ±1.53) mg · kg-1 · min-1] in OB-KPD patients were lower than those in OB-DM group[(697.06-± 231.9) mIU/L,(6.53 ± 2.21)mg · kg 1 · min-1,P＜0.0 1],but slightly higher than the Lean-KPD group [AUCins0 10min (92.1 ±29.8) mUU/L,GIR (2.55 ± 1.49) mg · kg 1 · min-1,P＜0.05].Glucose disposal rate (GDR) was strongly associated with casual plasma glucose (r =-0.502,P＜0.01),HbA1C(r =-0.553,P＜0.0 1) and FFA eoneentrations (r=-0.504,P＜0.01) on admission.Conclusions Insulin resistance and β-cell dysfunction coexist in all KPD patients.OB-KPD patients exhibit more severe insulin resistance,while Lean-KPD patients have lower insulin secretion.KPD patients had severe hyperglycemia,hypertriglyceridemia,and high plasma FFA levels on admission,suggesting that hyperglycemia and elevated FFA levels could result in serious insulin resistance,β-cell dysfunction,and diabetic ketosis in patients with KPD.

Components of free fatty acids (FFA) were examined by reverse high performance liquid chromatography in 25 patients with type 2 diabetes and 25 control subjects.The changes in components of FFA were observed before treatment, at 3 months and 1 year after treatment with pioglitazone in type 2 diabetic patients.The serum lauric acid, myristic acid and stearic acid levels were much higher in the diabetic patients than those in control subjects.Pioglitazone could decrease the levels of these fatty acids in the patients with type 2 diabetes mellitus.

Objective To evaluate the efficacy and safety of ureteral stenting after transurethral resection ( TUR) of bladder tumors involving the ureteral orifice.Methods From March 2009 to November 2015,34 cases of non-muscle invasive bladder tumor including 28 male and 6 female aged from 26 to 79 years( mean 51 years) were treated by TUR.14 cases had single tumor and 20 had multiple tumors,and 29 were primary and 5 were recurrent.All the patients had tumors involving the ureteral orifice without preoperative hydronephrosis revealed by IVU or CTU examination.The tumors were resected into the deep muscle layer and the involved ureteral orifices were resected during the procedure,and after that a double-J ureteral stent was placed in 18 cases.All patients received one immediate intravesical instillation of 50mg epirubicin after TUR, and further scheme of adjuvant intravesical chemotherapy instillations were made according to the pathological diagnosis.Ureteral stents were removed 10-12 weeks after TUR,and cystoscopy and urinary tract ultrasound examinations were performed every 3 months for 1-2 years postoperatively. Results The operations were successful without complications.No serious adverse reaction occurred in immediate and further adjuvant intravesical chemotherapy.During the follow-up period of 3-71 months, no ureteral stricture, hydronephrosis or tumor recurrence in the upper urinary tract occurred in all the 18 patients with ureteral stent, and the resected ureteral orifices recovered well with normal appearance and ejecting urine.Hydronephrosis was observed in 3 of 16 patients without ureteral stent including 2 cases of nontumoral stenosis at the ureterovesical junction requiring ureteral reimplantation and 1 case of lower ureteral tumor on the involved side requiring nephroureterectomy and bladder cuff excision.No patient complained of symptoms secondary to vesicoureteral reflux or continuous unrelievable lower urinary tract symptoms.2 cases of bladder tumor recurred out of the resected area.Conclusions Ureteral stenting after TUR of bladder tumors involving the ureteral orifice can prevent stricture at the ureterovesical junction without increasing the risk of tumor cell seeding along the upper urinary tract.The existence of a double-J ureteral stent does not increase complications of adjuvant intravesical chemotherapy, and also won't cause intolerable lower urinary tract symptoms.

Objective:To investigate the methods and complications of ultrasound-guided percutaneous nephrostomy (PCN) for treat-ing cancer-related hydronephrosis. Methods:From June 2003 to December 2015, 289 patients (342 kidneys) with cancer-related hy-dronephrosis were treated by ultrasound-guided PCN in Fujian Provincial Hospital. Among the 97 cases of renal insufficiency, 4 pa-tients were treated with hemodialysis before PCN. Except for the anterior mid calyx of nine kidneys in nine patients, the posterior mid or lower pole calyx of all other kidneys was punctured with ultrasound guidance. With the one-step PCN technique, 8F pigtail nephros-tomy tubes were placed into six kidneys in six patients;with the Seldinger PCN technique, 14F balloon and Malecot catheters were placed into 25 kidneys in 25 patients and 311 kidneys in 258 patients, respectively. Results:No severe bleeding and injury in the intes-tine, liver, spleen, pleura, or lung occurred. Two pigtail tubes were blocked one week after PCN. Seven balloon catheters failed to drain well because of the tip and balloon of the catheters located in the proximal part of the dilated ureters. Four balloons slipped out of the collection system of the kidney because of the auto-deflation of three balloons and one case of meager renal parenchyma failing to hold the balloon after a severe hydronephrosis was emptied. All, except 1, Malecot catheter drained well, and 8/9 PCNs through anteri-or mid calyx were successful. Serum creatinine levels were significantly decreased in all the 97 patients with renal insufficiency, of which 81 cases returned to normal, and no one needed persistent hemodialysis. Conclusion:Ultrasound-guided PCN is safe and effec-tive for treating cancer-related hydronephrosis. For appropriately selected patients, puncturing the anterior mid calyx may be an op-tion without additional complications. One-step pigtail nephrostomy tubes are recommended for patients with poor systemic condi-tions. For patients with long life expectancy or suspected complicated urinary infection, large sized Malecot catheters should be consid-ered.

Objective A multicenter, randomized, controlled and open-labled clinical trial was performed to compare the efficacy and safety of recombinant human insulin injection ( Yousilin R) and treated with Yousilin R versus Novolin R for 12 weeks respectively. Results Compared with baseline,the levels of glycosylated hemoglobin A1c ( HbA1c ) at the end of 12 weeks treatment decreased from 10. 77% to 7. 72% ( P ＜0. 05 ) in Yousilin R group and from 10. 33% to 7. 62% ( P ＜0. 05 ) in Novolin R group,2-hour postprandial plasma glucose ( 2hPG ) decreased from 15.49 mmol/L to 9. 72 mmol/L ( P ＜ 0. 05 ) in Yousilin R group and from 15.33 mmol/L to 10. 07 mmol/L( P ＜ 0. 05 ) in Novolin R group, and fasting plasma glucose (FPG) decreased from 10. 90 mmol/L to 7. 31 mmol/L( P ＜0. 05 ) in Yousilin R group and from 10. 22 mmol/L to 7.21 mmol/L (P ＜0. 05) in Novolin R group. The changes of HbA1c, 2hPG and FPG from baseline to endpoint in Yousilin R group was similar to those in Novolin R group ( P ＞ 0. 05 ).Furthermore, hypoglycemic events(26. 42% vs 30. 48% ), other adverse events( 13.21%vs 16. 19% ) ,and serious adverse events( 1.89%vs 1.90% )were comparable between Yousilin R and Novolin R groups(P ＞0. 05 ). Conclusions Yousilin R has similar efficacy, safety and compliance profiles to Novolin R group in the treatment of diabetic patients.

This investigation was made in regard to the changes of plasma Leptin, Tumor Necrosis Factor-alpha (TNF-alpha) and Neuropeptide Y (NPY) levels and their association with insulin resistance and beta-cell secretion function in normal glucose tolerant first-degree relatives of familial type 2 diabetic pedigrees in Chengdu area. Levels of Leptin, TNF-alpha, NPY and lipids (TG, TC, HDL-C) were determined in 86 type 2 diabetic mellitus (DM) patients, 73 normal glucose tolerant (NGT) first-degree relatives in familial type 2 diabetic pedigrees and 65 normal controls (NC) from non-diabetic families. All of the subjects underwent 75 g oral glucose tolerance test (OGTT). Plasma glucose, immunoreactive insulin (IRI) and true insulin (TI) levels were also determined. Fasting glucose and TI levels were used to calculate homeostasis model assessment-insulin resistance (HOMA-IR) and HOMA-beta cell indexes. After being adjusted for age and body mass index (BMI), the levels of Leptin in DM and NGT first-degree relatives were all significantly higher than that in normal controls (P < 0.05). Type 2 diabetic patients showed significantly elevated TNF-alpha levels than did the normal controls (P < 0.05). Furthermore, diabetic subjects showed significantly higher HOMA-IR and lower HOMA-B levels, compared with those in NGT and NC groups (P < 0.05). No statistically significant difference was found in regard to NPY among three groups. NGT first-degree relatives showed significantly higher levels of TG, fasting IRI, OGTT-2h IRI and HOMA-IR than did the normal controls (P < 0.05). Leptin was positively correlated with age, BMI, waist, A1c, fasting and OGTT-2h glucose, OGTT-2h TI and TNF-alpha in all subjects, and was negatively correlated with HOMA-B in females. Leptin levels were significantly elevated in NGT first-degree relatives, which implied that genetic defects of Leptin may play a role in the development of familial type 2 diabetic pedigrees.
Adult ; Case-Control Studies ; Diabetes Mellitus, Type 2 ; blood ; genetics ; Female ; Glucose Tolerance Test ; Humans ; Insulin ; secretion ; Insulin Resistance ; Leptin ; blood ; Male ; Middle Aged ; Neuropeptide Y ; blood ; Pedigree ; Tumor Necrosis Factor-alpha ; blood

OBJECTIVETo investigate the association between L296Q polymorphism in the cholesterol ester transfer protein(CETP)gene and type 2 diabetes mellitus(T2DM)and blood lipids.

METHODSPlasma glucose and lipid levels were measured in a total of 303 subjects recruited from the West China Hospital of Sichuan University. The subjects were divided into 4 groups according to the levels of plasma glucose and triglyceride, namely T2DM with hypertriglyceridemia group, group of T2DM with normal triglyceride, group of hypertriglyceridemia without DM and group of normal controls, respectively. Genotypes of L296Q polymorphism in the CETP gene of all subjects were analyzed by real-time fluorescent quantitative PCR(FQ-PCR).

RESULTSNo significant differences were observed in the frequencies of genotypes LL and LQ and the 296Q allele among the four groups (chi-square=3.459, P>0.05; chi-square=3.155, P>0.05, respectively), nor the frequencies of genotypes LL and LQ between the T2DM and non-T2DM, or plasma lipid levels between the 296Q allele carriers and those of genotype LL.

CONCLUSIONNo association was found between the L296Q polymorphism in the CETP gene and T2DM as well as plasma lipid levels in various groups of Chinese in this study.

Asian Continental Ancestry Group ; genetics ; Base Sequence ; Case-Control Studies ; Cholesterol Ester Transfer Proteins ; genetics ; Diabetes Mellitus, Type 2 ; blood ; genetics ; pathology ; Female ; Gene Frequency ; Genotype ; Humans ; Lipids ; blood ; Male ; Middle Aged ; Phenotype ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA