Aim: To investigate the clinical characteristics of diabetic patients with a low-titer positive for the anti-glutamic acid decarboxylase 65 antibody (GAD antibody). Methods: The subjects were 420 diabetic inpatients. ...Aim: To investigate the clinical characteristics of diabetic patients with a low-titer positive for the anti-glutamic acid decarboxylase 65 antibody (GAD antibody). Methods: The subjects were 420 diabetic inpatients. The endogenous insulin secretion was estimated on the basis of the C-peptide immunoreactivity from a 24 h urine collection (uCPR). Clinical variables were compared between patients negative for the GAD antibody (GAD antibody titer < 1.5 U/mL), a low-titer positive GAD antibody (1.5 U/mL ≤ GAD antibody titer < 10 U/mL) and a high-titer positive GAD antibody (10 U/mL ≤ GAD antibody titer). Results: The low and high-titer positive GAD antibodies were found in 25 and 10 patients, respectively. The uCPR was significantly lower in both the patients with a low (37 ± 33 ug/24h) and high-titer (39 ± 27 ug/24h) positive GAD antibodies than in those negative for GAD antibodies (71 ± 52 ug/24h). The uCPR level was significantly lower in the low-titer positive GAD antibody group (29 ± 22 ug/24h) than in the negative group (67 ± 55 ug/24h) among the patients not taking insulin secretagogues. The difference disappeared in the subjects taking insulin secreagogues. In the stepwise multiple regression analysis, a low-titer positive GAD antibody was independently associated with the uCPR level. Conclusions: Endogenous insulin secretion is reduced in diabetic patients positive for GAD antibodies, even if the titer is low. Earlier initiation of insulin therapy might therefore protect the pancreatic β-cell function in diabetic patients with a low-titer positive GAD antibody.展开更多
Objective: To improve the recognition of clinicians on insulin autoimmune syndrome (IAS) induced by exogenous insulin. Methods: Two cases of IAS induced by exogenous insulin were retrospectively analyzed. Results: Two...Objective: To improve the recognition of clinicians on insulin autoimmune syndrome (IAS) induced by exogenous insulin. Methods: Two cases of IAS induced by exogenous insulin were retrospectively analyzed. Results: Two patients had hypoglycemia occurred during the night. They had dissociation between C-peptide and insulin, accompanied by high titer of insulin autoantibody (IAA). Hypoglycemia episodes were ameliorated after the use of oral hypo-glycemic agents. Conclusions: Due to the role of insulin to be covered up, diabetes patients after the application of exogenous insulin induced IAS are easily misdiagnosed, high titer IAA and insulin and C-peptide separation phenomenon have been confirmed with diagnostic value.展开更多
BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabet...BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.展开更多
Hepatocellular carcinoma(HCC) is the third leading cause of cancer-related deaths worldwide. Only 30%-40% of the patients with HCC are eligible for curative treatments, which include surgical resection as the first op...Hepatocellular carcinoma(HCC) is the third leading cause of cancer-related deaths worldwide. Only 30%-40% of the patients with HCC are eligible for curative treatments, which include surgical resection as the first option, liver transplantation and percutaneous ablation. Unfortunately, there is a high frequency of tumor recurrence after surgical resection and most HCC seem resistant to conventional chemotherapy and radiotherapy. Sorafenib, a multi-tyrosine kinase inhibitor, is the only chemotherapeutic option for patients with advanced hepatocellular carcinoma. Patients treated with Sorafenib have a significant increase in overall survival of about three months. Therefore, there is an urgent need to develop alternative treatments. Due to its role in cell growth and development, the insulin-like growth factor system is commonly deregulated in many cancers. Indeed, the insulin-like growth factor(IGF) axis has recently emerged as a potential target for hepatocellular carcinoma treatment. To this aim, several inhibitors of the pathway have been developed suchas monoclonal antibodies, small molecules, antisense oligonucleotides or small interfering RNAs. However recent studies suggest that, unlike most tumors, HCC development requires increased signaling through insulin growth factor Ⅱ rather than insulin growth factor Ⅰ. This may have great implications in the future treatment of HCC. This review summarizes the role of the IGF axis in liver carcinogenesis and the current status of the strategies designed to target the IGF-Ⅰ signaling pathway for hepatocellular carcinoma treatment.展开更多
The reactivity of human preformed natural antibodies (PNAbs) with various porcine pancreatic cells and its isotypes was investigated. Eighteen serum samples from patients with insulin dependent diabetes mellitus (IDD...The reactivity of human preformed natural antibodies (PNAbs) with various porcine pancreatic cells and its isotypes was investigated. Eighteen serum samples from patients with insulin dependent diabetes mellitus (IDDM) and 20 serum samples from healthy human subjects were collected. The frozen sections of the pig pancreas were incubated with these sera, and subsequently incubated with FITC conjugated goat antihuman IgG and IgM monoclonal antibodies. The reactivity of human PNAbs with various porcine pancreatic cells was determined by indirect immunofluorescence staining technique. The results showed that 55.6 % of IDDM patients and 55.0 % of healthy human individuals contained PNAbs against porcine endocrine cells. However, the percentage of strongly reacting sera in the patient group was significantly increased as compared with that in the control group. All used sera from IDDM patients and 95 % of sera from healthy controls could react to one or more of the various pancreatic cell types, including: endocrine cells, exocrine cells, vascular endothelial cells, ductal epithelial cells and macrophages. The isotypes of PNAbs contained both IgG and IgM. In view of strongly positive reactivity of PNAbs with various porcine pancreatic cells, pretransplantly cross matching test and graft pretreatment may be necessary for survival of islet transplants.展开更多
Objective: Present Phase IV Trial is aimed at evaluating the immunogenicity, safety, and efficacy of Wockhardt’s insulin glargine, Glaritus®in comparison with reference insulin glargine, Lantus®in sub...Objective: Present Phase IV Trial is aimed at evaluating the immunogenicity, safety, and efficacy of Wockhardt’s insulin glargine, Glaritus®in comparison with reference insulin glargine, Lantus®in subjects with type 2 diabetes mellitus (T2DM), inadequately controlled on oral hypoglycaemics. Setting: A head-to-head, prospective, open-label, parallel group, randomized, Phase IV, non-inferiority study over 6 months treatment conducted in 10 centres in India. Participants: Considering 20% drop-out rate, 180 subjects of either sex, age 18 - 55 years, diagnosed with T2DM with body mass index (BMI) 18 - 38 kg/m2 and HbA1c levels 8.0% - 10.0% inadequately controlled by 1 or more oral hypoglycaemics and according to investigator needed glargine treatment were enrolled in the study. Interventions: Subjects self-administered insulin glargine (Glaritus®or Lantus®) subcutaneously once daily for 6 months. Treatment in Glaritus®arm was continued till 12 months. Percentage change in anti-insulin antibody (AIA) titre and HbA1C was ascertained at every 3 months interval. The tests were performed at accredited central laboratory. Treat-to-target dose titration: Starting doses of Glaritus®and Lantus®was 10 units (or 0.2 units/kg) once daily. The target fasting blood glucose was 70 to 130 mg/dL. Daily glargine dose was titrated by ±10% based on average of last 3 FBG values being out of target range and presence of nocturnal hypoglycemia. Early data trends: First interim analysis was planned once 100 subjects complete visit 8 (6 months treatment). By then, 119 subjects (78 males and 41 females) with mean age 46.3 years were enrolled, of which 90 (75.6%) subjects had evaluable data. The results of analysis indicated trend of comparability between Glaritus®and Lantus®at the end of 6 months in terms of immunogenicity (% change in AIA titre from baseline, −10.52 ± 23.06 vs. 0.48 ± 63.95), glycemic control (change in HbA1c from baseline, −1.09% ± 1.29% vs. 0.63% ± 1.19%) and hypoglycemic events (reported by 1 vs. 2 patients), respectively. Conclusion: The present study represents a robust design in line with international guidelines on biosimilar insulin development and the early data trends presents expected similarity of Glaritus®in immunogenicity, efficacy and safety to that of Lantus®in treatment of T2DM.展开更多
文摘Aim: To investigate the clinical characteristics of diabetic patients with a low-titer positive for the anti-glutamic acid decarboxylase 65 antibody (GAD antibody). Methods: The subjects were 420 diabetic inpatients. The endogenous insulin secretion was estimated on the basis of the C-peptide immunoreactivity from a 24 h urine collection (uCPR). Clinical variables were compared between patients negative for the GAD antibody (GAD antibody titer < 1.5 U/mL), a low-titer positive GAD antibody (1.5 U/mL ≤ GAD antibody titer < 10 U/mL) and a high-titer positive GAD antibody (10 U/mL ≤ GAD antibody titer). Results: The low and high-titer positive GAD antibodies were found in 25 and 10 patients, respectively. The uCPR was significantly lower in both the patients with a low (37 ± 33 ug/24h) and high-titer (39 ± 27 ug/24h) positive GAD antibodies than in those negative for GAD antibodies (71 ± 52 ug/24h). The uCPR level was significantly lower in the low-titer positive GAD antibody group (29 ± 22 ug/24h) than in the negative group (67 ± 55 ug/24h) among the patients not taking insulin secretagogues. The difference disappeared in the subjects taking insulin secreagogues. In the stepwise multiple regression analysis, a low-titer positive GAD antibody was independently associated with the uCPR level. Conclusions: Endogenous insulin secretion is reduced in diabetic patients positive for GAD antibodies, even if the titer is low. Earlier initiation of insulin therapy might therefore protect the pancreatic β-cell function in diabetic patients with a low-titer positive GAD antibody.
文摘Objective: To improve the recognition of clinicians on insulin autoimmune syndrome (IAS) induced by exogenous insulin. Methods: Two cases of IAS induced by exogenous insulin were retrospectively analyzed. Results: Two patients had hypoglycemia occurred during the night. They had dissociation between C-peptide and insulin, accompanied by high titer of insulin autoantibody (IAA). Hypoglycemia episodes were ameliorated after the use of oral hypo-glycemic agents. Conclusions: Due to the role of insulin to be covered up, diabetes patients after the application of exogenous insulin induced IAS are easily misdiagnosed, high titer IAA and insulin and C-peptide separation phenomenon have been confirmed with diagnostic value.
基金Supported by The National Key R and D Program of China,No.2018YFC1314103The National Natural Science Foundation of China,No.81870563 and No.82270838.
文摘BACKGROUND Insulin antibodies(IAs)affect blood glucose control in patients receiving insulin therapy.AIM To investigate the relationship between different hypoglycemic treatments and IAs in patients with type 2 diabetes mellitus(T2DM).METHODS This cross-sectional,retrospective study included 1863 patients with T2DM who were receiving exogenous insulin therapy.All patients received stable antidiabetic therapy in the last 3 months and IA levels were measured using an iodine-125 array.RESULTS A total of 1863 patients were enrolled.There were 902(48.4%)patients who had positive IAs(IA level>5%),with a mean IA level of 11.06%(10.39%-11.72%).IA levels were positively correlated with high fasting blood glucose(odds ratio=1.069,P<0.001).The proportion of positive IAs was lowest in patients using glargine only(31.9%)and highest in patients using human insulin only(70.3%),P<0.001.The IA levels in patients using sulfonylureas/glinides(8.3%),metformin(9.6%),and dipeptidyl peptidase-4 inhibitors(8.2%)were all lower than in patients without these drugs(all P<0.05).CONCLUSION Nearly half of patients on insulin therapy have positive IA antibodies,and IA antibody levels are associated with blood glucose control.Insulin glargine and a combination of oral glucose-lowering drugs were correlated with lower IA levels.
基金Supported by Ministerio de Ciencia e Innovacion BIO2009/09295 and SAF2012-40003FEDER funding,funds from the"UTE project CIMA"+1 种基金the project RNAREG(CSD2009-00080)from The Ministry of Science and Innovation under the programme CONSOLIDER INGENIO 2010
文摘Hepatocellular carcinoma(HCC) is the third leading cause of cancer-related deaths worldwide. Only 30%-40% of the patients with HCC are eligible for curative treatments, which include surgical resection as the first option, liver transplantation and percutaneous ablation. Unfortunately, there is a high frequency of tumor recurrence after surgical resection and most HCC seem resistant to conventional chemotherapy and radiotherapy. Sorafenib, a multi-tyrosine kinase inhibitor, is the only chemotherapeutic option for patients with advanced hepatocellular carcinoma. Patients treated with Sorafenib have a significant increase in overall survival of about three months. Therefore, there is an urgent need to develop alternative treatments. Due to its role in cell growth and development, the insulin-like growth factor system is commonly deregulated in many cancers. Indeed, the insulin-like growth factor(IGF) axis has recently emerged as a potential target for hepatocellular carcinoma treatment. To this aim, several inhibitors of the pathway have been developed suchas monoclonal antibodies, small molecules, antisense oligonucleotides or small interfering RNAs. However recent studies suggest that, unlike most tumors, HCC development requires increased signaling through insulin growth factor Ⅱ rather than insulin growth factor Ⅰ. This may have great implications in the future treatment of HCC. This review summarizes the role of the IGF axis in liver carcinogenesis and the current status of the strategies designed to target the IGF-Ⅰ signaling pathway for hepatocellular carcinoma treatment.
基金a grantfrom the National Natural Science Foundation of China(No.39370 70 2 )
文摘The reactivity of human preformed natural antibodies (PNAbs) with various porcine pancreatic cells and its isotypes was investigated. Eighteen serum samples from patients with insulin dependent diabetes mellitus (IDDM) and 20 serum samples from healthy human subjects were collected. The frozen sections of the pig pancreas were incubated with these sera, and subsequently incubated with FITC conjugated goat antihuman IgG and IgM monoclonal antibodies. The reactivity of human PNAbs with various porcine pancreatic cells was determined by indirect immunofluorescence staining technique. The results showed that 55.6 % of IDDM patients and 55.0 % of healthy human individuals contained PNAbs against porcine endocrine cells. However, the percentage of strongly reacting sera in the patient group was significantly increased as compared with that in the control group. All used sera from IDDM patients and 95 % of sera from healthy controls could react to one or more of the various pancreatic cell types, including: endocrine cells, exocrine cells, vascular endothelial cells, ductal epithelial cells and macrophages. The isotypes of PNAbs contained both IgG and IgM. In view of strongly positive reactivity of PNAbs with various porcine pancreatic cells, pretransplantly cross matching test and graft pretreatment may be necessary for survival of islet transplants.
文摘Objective: Present Phase IV Trial is aimed at evaluating the immunogenicity, safety, and efficacy of Wockhardt’s insulin glargine, Glaritus®in comparison with reference insulin glargine, Lantus®in subjects with type 2 diabetes mellitus (T2DM), inadequately controlled on oral hypoglycaemics. Setting: A head-to-head, prospective, open-label, parallel group, randomized, Phase IV, non-inferiority study over 6 months treatment conducted in 10 centres in India. Participants: Considering 20% drop-out rate, 180 subjects of either sex, age 18 - 55 years, diagnosed with T2DM with body mass index (BMI) 18 - 38 kg/m2 and HbA1c levels 8.0% - 10.0% inadequately controlled by 1 or more oral hypoglycaemics and according to investigator needed glargine treatment were enrolled in the study. Interventions: Subjects self-administered insulin glargine (Glaritus®or Lantus®) subcutaneously once daily for 6 months. Treatment in Glaritus®arm was continued till 12 months. Percentage change in anti-insulin antibody (AIA) titre and HbA1C was ascertained at every 3 months interval. The tests were performed at accredited central laboratory. Treat-to-target dose titration: Starting doses of Glaritus®and Lantus®was 10 units (or 0.2 units/kg) once daily. The target fasting blood glucose was 70 to 130 mg/dL. Daily glargine dose was titrated by ±10% based on average of last 3 FBG values being out of target range and presence of nocturnal hypoglycemia. Early data trends: First interim analysis was planned once 100 subjects complete visit 8 (6 months treatment). By then, 119 subjects (78 males and 41 females) with mean age 46.3 years were enrolled, of which 90 (75.6%) subjects had evaluable data. The results of analysis indicated trend of comparability between Glaritus®and Lantus®at the end of 6 months in terms of immunogenicity (% change in AIA titre from baseline, −10.52 ± 23.06 vs. 0.48 ± 63.95), glycemic control (change in HbA1c from baseline, −1.09% ± 1.29% vs. 0.63% ± 1.19%) and hypoglycemic events (reported by 1 vs. 2 patients), respectively. Conclusion: The present study represents a robust design in line with international guidelines on biosimilar insulin development and the early data trends presents expected similarity of Glaritus®in immunogenicity, efficacy and safety to that of Lantus®in treatment of T2DM.
