Anti-Human GLP-1(aa 9-18) monoclonal antibody

Objective: Studies have confirmed that endothelial progenitor cells (EPCs) are involved in diabetic complications. The present study assessed the action of the dipeptidyl peptidase-4 inhibitor sitagliptin on EPCs in newly diagnosed type 2 diabetes patients. Materials and methods: 60 newly-diagnosed type 2 diabetes patients were randomly divided into three treatment groups: sitagliptin (n = 20). metfonnin (n = 20), and combination sitagliptin and metfonnin (n = 20). Patients were treated once daily for 3 days. Before and after each treatment, the number of EPCs and concentration of soluble mediators (glucagon-like peptide 1 (GLP-1), nitric oxide (NO), endothelin-1 (ET-1), and stromal cell-derived factor-1 alpha (SDF-1 alpha)) were determined. Results: The number of CD34(+)KDR(+) and CD34(+)CD133(+)KDR(+) EPCs and concentration of GLP-1. NO, and SDF-1 alpha in sitagliptin and combination groups were both increased (both p < 0.05) but to a greater extent in the combination group (p < 0.05). Pearson correlation analysis and multiple linear regression analyses showed that the change in EPC numbers correlated with changes in peripheral GLP-1. NO. and SDF-1 alpha levels (p <0.05). Conclusion: Sitagliptin is able to directly increase the number of peripheral blood EPCs. This direct effect is to be important for lowering vascular risk in early diabetes before macrovascular complications appear.

Background:Congenital hyperinsulinism (CHI), a rare disease of excessive and dysregulated insulin secretion, can lead to prolonged and severe hypoglycemia. Dextrose infusions are a mainstay of therapy to restore normal glycemia, but can be associated with volume overload, especially in infants. By releasing intrahepatic glucose stores, glucagon infusions can reduce dependency on dextrose infusions. Recent studies have reported positive outcomes with glucagon infusions in patients with CHI; however, to date, there are no reports describing the clinical utility of titrated doses of infused glucagon to achieve glycemic stability. Objective:To assess the potential clinical utility of dose-titrated glucagon infusions in stabilizing glycemic status in pediatric patients with CHI, who were managed by medical and/or surgical approaches. Methods:Patients with CHI (N= 33), with or without mutations in the ATP-sensitive K(+)channel genes,ABCC8, andKCNJ11requiring glucagon by dose titration in addition to intravenous dextrose and medical therapy with diazoxide/octreotide to achieve glycemic stability were recruited. Following glucagon titration and a 24-h glucose stable period, glucose infusion rate (GIR) was reduced over a 24-h period. Achievement of glycemic stability and decrease in GIR were considered end points of the study. Results:All patients achieved glycemic stability with glucagon infusion, demonstrating clinical benefit. GIR reduced from 15.6 (4.5) to 13.4 (4.6) mg/kg/min mean (SD) (p= 0.00019 for difference;n= 32; pairedt-test) over 24 h. By univariate analysis, no individual baseline characteristic was associated with changes in the GIR. However, by baseline-adjusted modeling, mutational status of the patient (p= 0.011) was inversely associated with a reduction in GIR. Adverse events were infrequent with diarrhea possibly attributed to glucagon treatment in 1 patient. With long-term treatment following GIR reduction, necrolytic migratory erythema was observed in another patient. Conclusion:These data suggest that dose-titrated glucagon infusion therapy aids hypoglycemia prevention and reduction in GIR in the clinical management of patients with CHI.