胰岛素基础率是人工胰腺系统实现人体血糖闭环控制的基准,但该变量在临床治疗中难以准确确定.针对这一问题,本文设计了一种基于胰岛素基础率动态估计的人工胰腺自抗扰控制方法,通过扩张状态观测器(Extended state observer,ESO)实时估...胰岛素基础率是人工胰腺系统实现人体血糖闭环控制的基准,但该变量在临床治疗中难以准确确定.针对这一问题,本文设计了一种基于胰岛素基础率动态估计的人工胰腺自抗扰控制方法,通过扩张状态观测器(Extended state observer,ESO)实时估计血糖代谢过程中的内部与外界干扰,构建具备参数自适应能力的反馈控制律和胰岛素注射安全约束,实现血糖闭环调控能力的有效改善.在此基础上,本文设计了基于移动设备和蓝牙模块的人工胰腺软件系统,并通过美国食品药品监督管理局(Food and Drug Administration,FDA)接受的UVA/Padova T1DM仿真平台完成算法的比较仿真与功能测试.本文的工作将为后续人工胰腺临床试验的开展提供方法基础和技术支持,也为我国糖尿病患者血糖管理的改善提供精准医学治疗手段.展开更多
Insulin-loaded poly(lactide-co-glycolide) nanoparticles (INS-PLGA-NPs) were prepared by a double emulsion method (w/o/w), using ethyl acetate as organic solvent and poloxamer188 as emulsifier. Experimental parameter...Insulin-loaded poly(lactide-co-glycolide) nanoparticles (INS-PLGA-NPs) were prepared by a double emulsion method (w/o/w), using ethyl acetate as organic solvent and poloxamer188 as emulsifier. Experimental parameters such as the emulsifier and PLGA concentrations, the pH and concentration of the insulin solution, the solvent evaporation method and PVA in the internal phase were investigated for the encapsulation efficiency. The results indicated that higher emulsifier concentration, relatively less amount of PLGA and lower insulin concentration would increase the entrapment of insulin. Furthermore, pH of insulin solution approaching to pI (5.3), adding some PVA to the internal phase and a shorter evaporation time helped to enhance the incorporation efficiency of insulin. Optimized preparation parameters led to nanoparticles with well-defined characteristics such as an average size around 149.6 nm, a polydispersity lower than 0.1 and high encapsulation efficiency up to 42.8%.展开更多
AIM： To evaluate whether diabetic patients had a higher risk of colon cancer mortality and its associated risk factors. METHODS： The sex-specific crude and age-standard- ized （to the 2000 World Health Organization ...AIM： To evaluate whether diabetic patients had a higher risk of colon cancer mortality and its associated risk factors. METHODS： The sex-specific crude and age-standard- ized （to the 2000 World Health Organization popula- tion） mortality rates of colon cancer in the Taiwan Residents general population were first calculated from 1995 to 2006. The trends were evaluated by linear regression. A total of 113 347 diabetic men and 131 573 diabetic women aged ~〉 25 years at recruitment from 1995 to 1998 were followed up until the end of 2006. Age/sex- specific colon cancer mortality rate ratios were cal- culated comparing the mortality rates of the diabetic patients with the average mortality rates of the general population within 12 years （1995-2006）. A sub-cohort of diabetic patients （42 260 men and 49 405 women） was interviewed using a baseline questionnaire and Cox＇s regression was used to evaluate the risk factors for colon cancer mortality in these diabetic patients.RESULTS： The crude and age-standardized trends of colon cancer mortality from 1995 to 2006 increased significantly for both sexes in the general population. A total of 641 diabetic men and 573 diabetic women died of colon cancer, with a mortality rate of 74.4 and 54.3 per 100 000 person-years, respectively. Mortality rate ratios [95% confidence intervals （CIs）] showed a significantly higher risk of mortality from colon can- cer for the diabetic patients compared to the general population, with the magnitude increasing with de- creasing age： 1.65 （1.40-1.95）, 2.01 （1.78-2.27）, 2.75 （2.36-3.21） and 5.69 （4.65-6.96） for /〉 75, 65-74, 55-64 and 25-54 years old, respectively, for men; and 1.46 （1.24-1.72）, 2.09 （1.84-2.38）, 2.67 （2.27-3.14） and 3.05 （2.29-4.06）, respectively, for women. Among the sub-cohort of diabetic patients who had been in- terviewed with the baseline questionnaire, including information on age, sex, diabetes duration, diabe- tes type, body mass index, smoking, insulin use and area of residence, age and smoking were significantly predictive for colon cancer mortality, with respec- tive adjusted hazard ratios （HRs） （95% CIs） of 1.077 （1.066-1.088） and 1.384 （1.068-1.792）. Diabetes dura- tion became a significant factor when those who died of colon cancer within 5 years of diabetes diagnosis were excluded to minimize the possible contamination of diabetes caused by incipient colon cancer, with an adjusted hazard ratio of 1.021 （1.007-1.034）. Sex, dia- betes type, insulin use, body mass index and area of residence were not significant predictors for colon can- cer mortality in the diabetic patients. Although insulin use was categorized into subgroups of duration of use （non-users and users 〈 5 years, 5-9 years and i〉 10 years）, none of the HRs for colon cancer mortality was significant with regards to different durations of insulin use. CONCLUSION： Colon cancer mortality is increasing in Taiwan. A higher risk is observed in diabetic patients. Smoking, but not insulin use, is a modifiable risk factor.展开更多
Ultra rapid lispro(URLi)is a novel formulation of insulin lispro designed to more closely match the physiological insulin response to a meal,with the aim of improving postprandial glucose(PPG)control.We conducted a mu...Ultra rapid lispro(URLi)is a novel formulation of insulin lispro designed to more closely match the physiological insulin response to a meal,with the aim of improving postprandial glucose(PPG)control.We conducted a multinational,multicenter,randomized,double-blind,treat-to-target,26-week,phase 3 trial to evaluate the efficacy and safety of URLi in adults with type 2 diabetes(T2D).After an 8-week lead-in period during which basal insulin glargine or degludec was optimized,adults with T2D were randomized(2:1)to prandial URLi(n=395)or lispro(n=200).The primary endpoint was non-inferiority of URLi versus lispro in glycated hemoglobin A1c(HbA_(1c))change from baseline to week 26.Multiplicity-adjusted analyses were performed to assess the superiority of URLi in 1-and 2-h PPG excursions during a mixed-meal tolerance test(MMTT)and HbA_(1c) change at week 26.URLi showed non-inferiority for Hb Achange at week 26 versus lispro(least-squares mean[LSM]difference,0.07%;95%confidence interval:-0.07,0.21).HbA_(1c) was reduced by 0.56%and 0.63%with URLi and lispro,respectively,with no significant treatment difference(P=0.321).URLi provided superior PPG excursion control versus lispro at1 h(LSM difference:-14.6 mg/d L,P<0.001)and 2 h(LSM difference:-21.8 mg/d L,P<0.001)as well as other time points(30–240 min)during the MMTT.Incremental area under the glucose curve during the MMTT was also significantly lower with URLi versus lispro.The safety profiles were generally similar between treatment groups.In conclusion,URLi was superior to lispro for PPG control,with noninferiority in HbA_(1c) improvement,in adults with T2D.展开更多
Background:Most Chinese patients with type 2 diabetes mellitus(T2DM)have mild obesity and central obesity.Central obesity is combined with insulin resistance.The aim of this study was to assess the effect of abdominal...Background:Most Chinese patients with type 2 diabetes mellitus(T2DM)have mild obesity and central obesity.Central obesity is combined with insulin resistance.The aim of this study was to assess the effect of abdominal adipose tissue on insulin-sensitivity improvement after Roux-en-Y gastric bypass(RYGB)in Chinese diabetic patients with mild and central obesity.Methods:Seventeen T2DM patients with a mean body mass index of 30.3 kg/m^(2) were scheduled for laparoscopic RYGB.A hyperinsulinemic-euglycemic clamp and dual-energy X-ray absorptiometry were performed prior to surgery and 3 months after RYGB.The primary end points were the correlations between insulin sensitivity and abdominal adipose tissue,including visceral adipose tissue(VAT)and subcutaneous adipose tissue(SAT),before and 3 months after RYGB.Results:Indices of peripheral insulin sensitivity,including glucose-disposal rate(M value)and glucose infusion rate,were significantly increased after RYGB.Body-fat mass,VAT and SAT were significantly reduced after RYGB.The pre-operative M value was significantly correlated with VAT mass(r=–0.57,P=0.02),but not correlated with SAT mass.M value changes after RYGB were highly correlated with changes in VAT mass(r=–0.59,P=0.01),percentage of VAT mass(r=–0.66,P<0.01),VAT area(r=–0.56,P=0.02)and percentage of VAT area(r=–0.57,P=0.02).Conclusions:A significant correlation was observed between increased peripheral insulin sensitivity and decreased VAT following RYGB in Chinese patients with mild and central obesity.VAT and SAT were significantly decreased with improved insulin sensitivity after RYGB.VAT mass may be considered as an indication for gastric bypass during patient selection.展开更多
文摘胰岛素基础率是人工胰腺系统实现人体血糖闭环控制的基准,但该变量在临床治疗中难以准确确定.针对这一问题,本文设计了一种基于胰岛素基础率动态估计的人工胰腺自抗扰控制方法,通过扩张状态观测器(Extended state observer,ESO)实时估计血糖代谢过程中的内部与外界干扰,构建具备参数自适应能力的反馈控制律和胰岛素注射安全约束,实现血糖闭环调控能力的有效改善.在此基础上,本文设计了基于移动设备和蓝牙模块的人工胰腺软件系统,并通过美国食品药品监督管理局(Food and Drug Administration,FDA)接受的UVA/Padova T1DM仿真平台完成算法的比较仿真与功能测试.本文的工作将为后续人工胰腺临床试验的开展提供方法基础和技术支持,也为我国糖尿病患者血糖管理的改善提供精准医学治疗手段.
文摘Insulin-loaded poly(lactide-co-glycolide) nanoparticles (INS-PLGA-NPs) were prepared by a double emulsion method (w/o/w), using ethyl acetate as organic solvent and poloxamer188 as emulsifier. Experimental parameters such as the emulsifier and PLGA concentrations, the pH and concentration of the insulin solution, the solvent evaporation method and PVA in the internal phase were investigated for the encapsulation efficiency. The results indicated that higher emulsifier concentration, relatively less amount of PLGA and lower insulin concentration would increase the entrapment of insulin. Furthermore, pH of insulin solution approaching to pI (5.3), adding some PVA to the internal phase and a shorter evaporation time helped to enhance the incorporation efficiency of insulin. Optimized preparation parameters led to nanoparticles with well-defined characteristics such as an average size around 149.6 nm, a polydispersity lower than 0.1 and high encapsulation efficiency up to 42.8%.
基金Supported by The Department of Health of Taiwan,No. DOH97-TD-D-113-97009
文摘AIM： To evaluate whether diabetic patients had a higher risk of colon cancer mortality and its associated risk factors. METHODS： The sex-specific crude and age-standard- ized （to the 2000 World Health Organization popula- tion） mortality rates of colon cancer in the Taiwan Residents general population were first calculated from 1995 to 2006. The trends were evaluated by linear regression. A total of 113 347 diabetic men and 131 573 diabetic women aged ~〉 25 years at recruitment from 1995 to 1998 were followed up until the end of 2006. Age/sex- specific colon cancer mortality rate ratios were cal- culated comparing the mortality rates of the diabetic patients with the average mortality rates of the general population within 12 years （1995-2006）. A sub-cohort of diabetic patients （42 260 men and 49 405 women） was interviewed using a baseline questionnaire and Cox＇s regression was used to evaluate the risk factors for colon cancer mortality in these diabetic patients.RESULTS： The crude and age-standardized trends of colon cancer mortality from 1995 to 2006 increased significantly for both sexes in the general population. A total of 641 diabetic men and 573 diabetic women died of colon cancer, with a mortality rate of 74.4 and 54.3 per 100 000 person-years, respectively. Mortality rate ratios [95% confidence intervals （CIs）] showed a significantly higher risk of mortality from colon can- cer for the diabetic patients compared to the general population, with the magnitude increasing with de- creasing age： 1.65 （1.40-1.95）, 2.01 （1.78-2.27）, 2.75 （2.36-3.21） and 5.69 （4.65-6.96） for /〉 75, 65-74, 55-64 and 25-54 years old, respectively, for men; and 1.46 （1.24-1.72）, 2.09 （1.84-2.38）, 2.67 （2.27-3.14） and 3.05 （2.29-4.06）, respectively, for women. Among the sub-cohort of diabetic patients who had been in- terviewed with the baseline questionnaire, including information on age, sex, diabetes duration, diabe- tes type, body mass index, smoking, insulin use and area of residence, age and smoking were significantly predictive for colon cancer mortality, with respec- tive adjusted hazard ratios （HRs） （95% CIs） of 1.077 （1.066-1.088） and 1.384 （1.068-1.792）. Diabetes dura- tion became a significant factor when those who died of colon cancer within 5 years of diabetes diagnosis were excluded to minimize the possible contamination of diabetes caused by incipient colon cancer, with an adjusted hazard ratio of 1.021 （1.007-1.034）. Sex, dia- betes type, insulin use, body mass index and area of residence were not significant predictors for colon can- cer mortality in the diabetic patients. Although insulin use was categorized into subgroups of duration of use （non-users and users 〈 5 years, 5-9 years and i〉 10 years）, none of the HRs for colon cancer mortality was significant with regards to different durations of insulin use. CONCLUSION： Colon cancer mortality is increasing in Taiwan. A higher risk is observed in diabetic patients. Smoking, but not insulin use, is a modifiable risk factor.
文摘Ultra rapid lispro(URLi)is a novel formulation of insulin lispro designed to more closely match the physiological insulin response to a meal,with the aim of improving postprandial glucose(PPG)control.We conducted a multinational,multicenter,randomized,double-blind,treat-to-target,26-week,phase 3 trial to evaluate the efficacy and safety of URLi in adults with type 2 diabetes(T2D).After an 8-week lead-in period during which basal insulin glargine or degludec was optimized,adults with T2D were randomized(2:1)to prandial URLi(n=395)or lispro(n=200).The primary endpoint was non-inferiority of URLi versus lispro in glycated hemoglobin A1c(HbA_(1c))change from baseline to week 26.Multiplicity-adjusted analyses were performed to assess the superiority of URLi in 1-and 2-h PPG excursions during a mixed-meal tolerance test(MMTT)and HbA_(1c) change at week 26.URLi showed non-inferiority for Hb Achange at week 26 versus lispro(least-squares mean[LSM]difference,0.07%;95%confidence interval:-0.07,0.21).HbA_(1c) was reduced by 0.56%and 0.63%with URLi and lispro,respectively,with no significant treatment difference(P=0.321).URLi provided superior PPG excursion control versus lispro at1 h(LSM difference:-14.6 mg/d L,P<0.001)and 2 h(LSM difference:-21.8 mg/d L,P<0.001)as well as other time points(30–240 min)during the MMTT.Incremental area under the glucose curve during the MMTT was also significantly lower with URLi versus lispro.The safety profiles were generally similar between treatment groups.In conclusion,URLi was superior to lispro for PPG control,with noninferiority in HbA_(1c) improvement,in adults with T2D.
基金supported by the New Xiangya Talent Projects of Third Xiangya Hospital of Central South University(grant number JY201628).
文摘Background:Most Chinese patients with type 2 diabetes mellitus(T2DM)have mild obesity and central obesity.Central obesity is combined with insulin resistance.The aim of this study was to assess the effect of abdominal adipose tissue on insulin-sensitivity improvement after Roux-en-Y gastric bypass(RYGB)in Chinese diabetic patients with mild and central obesity.Methods:Seventeen T2DM patients with a mean body mass index of 30.3 kg/m^(2) were scheduled for laparoscopic RYGB.A hyperinsulinemic-euglycemic clamp and dual-energy X-ray absorptiometry were performed prior to surgery and 3 months after RYGB.The primary end points were the correlations between insulin sensitivity and abdominal adipose tissue,including visceral adipose tissue(VAT)and subcutaneous adipose tissue(SAT),before and 3 months after RYGB.Results:Indices of peripheral insulin sensitivity,including glucose-disposal rate(M value)and glucose infusion rate,were significantly increased after RYGB.Body-fat mass,VAT and SAT were significantly reduced after RYGB.The pre-operative M value was significantly correlated with VAT mass(r=–0.57,P=0.02),but not correlated with SAT mass.M value changes after RYGB were highly correlated with changes in VAT mass(r=–0.59,P=0.01),percentage of VAT mass(r=–0.66,P<0.01),VAT area(r=–0.56,P=0.02)and percentage of VAT area(r=–0.57,P=0.02).Conclusions:A significant correlation was observed between increased peripheral insulin sensitivity and decreased VAT following RYGB in Chinese patients with mild and central obesity.VAT and SAT were significantly decreased with improved insulin sensitivity after RYGB.VAT mass may be considered as an indication for gastric bypass during patient selection.
