Background Early intensive insulin therapies in newly diagnosed type 2 diabetic patients may improve β-cell function and yield prolonged glycemic remissions. This study was performed to evaluate the relationship betw...Background Early intensive insulin therapies in newly diagnosed type 2 diabetic patients may improve β-cell function and yield prolonged glycemic remissions. This study was performed to evaluate the relationship between the glycemic remission and 13-cell function and assess the variables predictive of long-term near-normoglycemic remission. Methods Eighty-four newly diagnosed type 2 diabetic patients were treated with 2-week continuous subcutaneous insulin infusion （CSII） and followed up longitudinally. Intravenous glucose tolerance tests （IVGTTs） were performed, and blood glucose, hemoglobin Alc （HbAlc） and insulin were measured at baseline, after CSII and at 2-year visit. The patients who maintained glycemic control for two years were defined as the remission group and those who relapsed before the 2-year visit were the non-remission group. Results The duration to be diagnosed of the patients （from the time that patients began to have diabetic symptoms until diagnosis） in the remission group was shorter than that in the non-remission group （1.00 month vs 4.38 months, P=0.040）. The increase of the acute insulin response （AIR） was maintained after 2 years in the remission group compared with AIR measured immediately after intervention （413.05 pmol·L^-1·min^-1 vs 408.99 pmol·L^-1·min^-1, P=0.820）. While AIR in the non-remission group significantly declined （74.71 pmol·L^-1·min^-1 vs 335.64 pmol·L^-1·min^-1, P=0.030）. Cox model showed that a shorter duration to be diagnosed positively affected the duration of near-nomoglycemic remission with an odds ratio （OR） 1.019, P=0.038, while fasting plasma glucose （FPG） and post-breakfast plasma glucose （PPG） after CSII were the risk factors （OR 1.397, P=0.024 and OR 1.187, P=0.035, respectively）. Conclusion The near-normoglycemic remission is closely associated with long-term maintenance of β-cell function and occurs more commonly in patients with shorter duration to be diagnosed and better glycemic control during CSII.展开更多
Background Diabetes mellitus has become epidemic in recent years in China. We investigated the prevalence of hyperglycaemia and inadequate glycaemic control among type 2 diabetic inpatients from ten university teachin...Background Diabetes mellitus has become epidemic in recent years in China. We investigated the prevalence of hyperglycaemia and inadequate glycaemic control among type 2 diabetic inpatients from ten university teaching hospitals in Guangdong Province, China. Methods Inadequate glycaemic control in diabetic patients was defined as HbA1c 〉 6.5%. Therapeutic regimens included no-intervention, lifestyle only, oral antiglycemic agents （OA）, insulin plus OA （insulin＋OA）, or insulin only. Antidiabetic managements included monotherapy, double therapy, triple or quadruple therapy. Results Among 493 diabetic inpatients with known history, 75% had HbA1c ≥ 6.5%. inadequate glucose control rates were more frequently seen in patients on insulin＋OA regimen （97%） ,than on OA regimen （71%） （P 〈0.001）, and more frequent in patients on combination therapy （81%-96%） than monotherapy （7,5%） （P 〈0.0,5）. Patients on insulin differed significantly from patients on OA by mean HbA1c, glycemic control rate, diabetes duration, microvascular complications, and BMI （P 〈0.01）. Conclusions This study showed that glycaemic control of type 2 diabetic patients deteriorated for patients who received insulin and initiation time of insulin was usually delayed, it is up to clinicians to move from the traditional stepwise therapy to a more active and early combination antidiabetic therapy to provide better glucose control.展开更多
Background A new inhalable insulin aerosol （Inh-lns） was developed in China. The aim of this multicenter clinical study was to evaluate the efficacy and safety of this new Inh-lns as a treatment of type 2 diabetes. ...Background A new inhalable insulin aerosol （Inh-lns） was developed in China. The aim of this multicenter clinical study was to evaluate the efficacy and safety of this new Inh-lns as a treatment of type 2 diabetes. Regular porcine insulin （RI） was used as a control. Methods This study is a prospective, randomized, open-label, parallel-group multicenter clinical trial in which 253 qualified patients with type 2 diabetes received the insulin Glargine daily at bedtime plus either a pre-meal Inh-lns or a pre-meal subcutaneous RI for 12 weeks. HbAlc, fasting plasma glucose （FPG）, the 1-hour-postprandial blood glucose （1hPBG） and the 2-hour-postprandial blood glucose （2hPBG） were measured. Events were monitored for adverse effects. Results After 12 weeks, the HbAlc decreased significantly from baseline in both treatment groups, with no significant difference between the two regimens. In the Inh-lns group, FPG, both lhPBG and 2hPBG significantly declined from baseline after the 8th- and 12th-weeks of treatment. The reduced values of FPG or 1hPBG between the two groups showed a more significant hypoglycemic effect with the Inh-lns than the RI. After 12 weeks, the pulmonary carbon monoxide diffusing capacity （DLco） was significantly lower in Inh-lns group than in the RI. The main side effects of Inh-lns were coughing, excessive sputum, and hypoglycemia. Conclusions Inh-lns was effective in decreasing HbAlc like the RI. It was better in lowering the FPG and the lhPBG than the RI. Its main side effects were coughing, excessive sputum, and hypoglycemia. Also, Inh-lns slightly impaired DLco.展开更多
Background NF-KB p65 was shown to inhibit transcription of phosphoenolpyruvate carboxykinase （PEPCK）, a rate-limiting enzyme in gluconeogenesis in the liver. To understand the mechanism of action of NF-KB p65, we in...Background NF-KB p65 was shown to inhibit transcription of phosphoenolpyruvate carboxykinase （PEPCK）, a rate-limiting enzyme in gluconeogenesis in the liver. To understand the mechanism of action of NF-KB p65, we investigated the nuclear receptor corepressor in the regulation of PEPCK transcription. Methods Rat H411E cells, human hepatoma HepG2 cells and human embryo kidney （HEK） 293 cells were used in this study. The transcriptional activity of a rat PEPCK gene promoter （-490/＋100） was analyzed in HepG2 cells, a HepG2 super suppressor IkBa （sslkBa） stable cell line, and HEK 293 cells. The effects of p65 and sslkBa on a rat PEPCK gene promoter were observed using the PEPCK luciferase reporter system. The interaction of the cAMP-response- element-binding （CREB） protein, histone deacetylase 3 （HDAC3） and silencing mediator for retinoic and thyroid hormone receptors （SMRT） with the PEPCK gene promoter were investigated using the chromatin immunoprecipitation （CHIP） assay, p65 cotransfection and RNAi-mediated gene knockdown were used to determine the corepressor involved in the inhibition of PEPCK by NF-KB p65 and the transcriptional regulation of CREB by NF-KB p65. Results NF-KB p65 inhibited PEPCK expression and the inhibition was blocked by sslkBa. The inhibitory effect of p65 was completely blocked in a HepG2 stable cell line in which sslkBa was expressed. HDAC3 or SMRT knockdown led to a significant up-regulation of PEPCK reporter activity in the presence of p65 cotransfection. In the ChIP assay the interaction of HDAC3 and SMRT with the PEPCK gene promoter was induced by p65 activation, but the CREB signal was reduced. Transcriptional activity of CREB was inhibited by NF-kB p65 cotransfection. The inhibitory effect of NF-kB p65 was blocked by HDAC3 RNAi or SMRT RNAi. Conculsions The study showed that the inhibition of PEPCK by NF-kB p65 was dependent on HDAC3 and SMRT, which form a nuclear corepressor complex for transcriptional inhibition. The transcription factors NF-kB p65 and CREB share the same corepressor HDAC3-SMRT, and the corepressor exchange leads to inhibition of PEPCK gene transcription by NF-kB p65.展开更多
文摘Background Early intensive insulin therapies in newly diagnosed type 2 diabetic patients may improve β-cell function and yield prolonged glycemic remissions. This study was performed to evaluate the relationship between the glycemic remission and 13-cell function and assess the variables predictive of long-term near-normoglycemic remission. Methods Eighty-four newly diagnosed type 2 diabetic patients were treated with 2-week continuous subcutaneous insulin infusion （CSII） and followed up longitudinally. Intravenous glucose tolerance tests （IVGTTs） were performed, and blood glucose, hemoglobin Alc （HbAlc） and insulin were measured at baseline, after CSII and at 2-year visit. The patients who maintained glycemic control for two years were defined as the remission group and those who relapsed before the 2-year visit were the non-remission group. Results The duration to be diagnosed of the patients （from the time that patients began to have diabetic symptoms until diagnosis） in the remission group was shorter than that in the non-remission group （1.00 month vs 4.38 months, P=0.040）. The increase of the acute insulin response （AIR） was maintained after 2 years in the remission group compared with AIR measured immediately after intervention （413.05 pmol·L^-1·min^-1 vs 408.99 pmol·L^-1·min^-1, P=0.820）. While AIR in the non-remission group significantly declined （74.71 pmol·L^-1·min^-1 vs 335.64 pmol·L^-1·min^-1, P=0.030）. Cox model showed that a shorter duration to be diagnosed positively affected the duration of near-nomoglycemic remission with an odds ratio （OR） 1.019, P=0.038, while fasting plasma glucose （FPG） and post-breakfast plasma glucose （PPG） after CSII were the risk factors （OR 1.397, P=0.024 and OR 1.187, P=0.035, respectively）. Conclusion The near-normoglycemic remission is closely associated with long-term maintenance of β-cell function and occurs more commonly in patients with shorter duration to be diagnosed and better glycemic control during CSII.
文摘Background Diabetes mellitus has become epidemic in recent years in China. We investigated the prevalence of hyperglycaemia and inadequate glycaemic control among type 2 diabetic inpatients from ten university teaching hospitals in Guangdong Province, China. Methods Inadequate glycaemic control in diabetic patients was defined as HbA1c 〉 6.5%. Therapeutic regimens included no-intervention, lifestyle only, oral antiglycemic agents （OA）, insulin plus OA （insulin＋OA）, or insulin only. Antidiabetic managements included monotherapy, double therapy, triple or quadruple therapy. Results Among 493 diabetic inpatients with known history, 75% had HbA1c ≥ 6.5%. inadequate glucose control rates were more frequently seen in patients on insulin＋OA regimen （97%） ,than on OA regimen （71%） （P 〈0.001）, and more frequent in patients on combination therapy （81%-96%） than monotherapy （7,5%） （P 〈0.0,5）. Patients on insulin differed significantly from patients on OA by mean HbA1c, glycemic control rate, diabetes duration, microvascular complications, and BMI （P 〈0.01）. Conclusions This study showed that glycaemic control of type 2 diabetic patients deteriorated for patients who received insulin and initiation time of insulin was usually delayed, it is up to clinicians to move from the traditional stepwise therapy to a more active and early combination antidiabetic therapy to provide better glucose control.
文摘Background A new inhalable insulin aerosol （Inh-lns） was developed in China. The aim of this multicenter clinical study was to evaluate the efficacy and safety of this new Inh-lns as a treatment of type 2 diabetes. Regular porcine insulin （RI） was used as a control. Methods This study is a prospective, randomized, open-label, parallel-group multicenter clinical trial in which 253 qualified patients with type 2 diabetes received the insulin Glargine daily at bedtime plus either a pre-meal Inh-lns or a pre-meal subcutaneous RI for 12 weeks. HbAlc, fasting plasma glucose （FPG）, the 1-hour-postprandial blood glucose （1hPBG） and the 2-hour-postprandial blood glucose （2hPBG） were measured. Events were monitored for adverse effects. Results After 12 weeks, the HbAlc decreased significantly from baseline in both treatment groups, with no significant difference between the two regimens. In the Inh-lns group, FPG, both lhPBG and 2hPBG significantly declined from baseline after the 8th- and 12th-weeks of treatment. The reduced values of FPG or 1hPBG between the two groups showed a more significant hypoglycemic effect with the Inh-lns than the RI. After 12 weeks, the pulmonary carbon monoxide diffusing capacity （DLco） was significantly lower in Inh-lns group than in the RI. The main side effects of Inh-lns were coughing, excessive sputum, and hypoglycemia. Conclusions Inh-lns was effective in decreasing HbAlc like the RI. It was better in lowering the FPG and the lhPBG than the RI. Its main side effects were coughing, excessive sputum, and hypoglycemia. Also, Inh-lns slightly impaired DLco.
基金This study was supported by grants from the National Natural Science Foundation of China （No. 30570885）, 973 Program of China （No. 2006CB503902） （to WENG Jian-ping）, the National Institutes of Health Grant （No. DK068036） and American Diabetes Association Research Award （No. 7-04-RA-139） （to YE ,lian-ping）Acknowledgements： We would like to be grateful to Ms. Wei Tseng, Dr. HE Qin and Dr. YIN Jun for their excellent technical assistance.
文摘Background NF-KB p65 was shown to inhibit transcription of phosphoenolpyruvate carboxykinase （PEPCK）, a rate-limiting enzyme in gluconeogenesis in the liver. To understand the mechanism of action of NF-KB p65, we investigated the nuclear receptor corepressor in the regulation of PEPCK transcription. Methods Rat H411E cells, human hepatoma HepG2 cells and human embryo kidney （HEK） 293 cells were used in this study. The transcriptional activity of a rat PEPCK gene promoter （-490/＋100） was analyzed in HepG2 cells, a HepG2 super suppressor IkBa （sslkBa） stable cell line, and HEK 293 cells. The effects of p65 and sslkBa on a rat PEPCK gene promoter were observed using the PEPCK luciferase reporter system. The interaction of the cAMP-response- element-binding （CREB） protein, histone deacetylase 3 （HDAC3） and silencing mediator for retinoic and thyroid hormone receptors （SMRT） with the PEPCK gene promoter were investigated using the chromatin immunoprecipitation （CHIP） assay, p65 cotransfection and RNAi-mediated gene knockdown were used to determine the corepressor involved in the inhibition of PEPCK by NF-KB p65 and the transcriptional regulation of CREB by NF-KB p65. Results NF-KB p65 inhibited PEPCK expression and the inhibition was blocked by sslkBa. The inhibitory effect of p65 was completely blocked in a HepG2 stable cell line in which sslkBa was expressed. HDAC3 or SMRT knockdown led to a significant up-regulation of PEPCK reporter activity in the presence of p65 cotransfection. In the ChIP assay the interaction of HDAC3 and SMRT with the PEPCK gene promoter was induced by p65 activation, but the CREB signal was reduced. Transcriptional activity of CREB was inhibited by NF-kB p65 cotransfection. The inhibitory effect of NF-kB p65 was blocked by HDAC3 RNAi or SMRT RNAi. Conculsions The study showed that the inhibition of PEPCK by NF-kB p65 was dependent on HDAC3 and SMRT, which form a nuclear corepressor complex for transcriptional inhibition. The transcription factors NF-kB p65 and CREB share the same corepressor HDAC3-SMRT, and the corepressor exchange leads to inhibition of PEPCK gene transcription by NF-kB p65.
