Transplantation · 2008
The use of exenatide in islet transplant recipients with chronic allograft dysfunction: safety, efficacy, and metabolic effects.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Froud Tatiana, Faradji Raquel N, Pileggi Antonello, Messinger Shari, Baidal David A, Ponte Gaston M, Cure Pablo E, Monroy Kathy, Mendez Armando, Selvaggi Gennaro, Ricordi Camillo, Alejandro Rodolfo
Аннотация
BACKGROUND: A current limitation of islet transplantation is reduced long-term graft function. The glucagon-like peptide-1 receptor agonist, exenatide (Byetta, Amylin Pharmaceuticals, CA) has properties that could improve existing islet function, prevent further loss of islet mass and possibly even stimulate islet regeneration.
METHODS: This prospective study evaluated the safety, efficacy, and metabolic effects of exenatide in subjects with type 1 diabetes mellitus and islet allograft dysfunction requiring exogenous insulin.
RESULTS: Sixteen subjects commenced exenatide, 12 continue (follow-up 214+/-57 days; range 108-287), four (25%) discontinued medication because of side effects. At 6 months, exogenous insulin was significantly reduced with stable glycemic control (0.15+/-0.02 vs. 0.11+/-0.025 U/kg per day; P<0.0001); three subjects discontinued insulin from 4, 5, and 9 U/day, respectively, two sustained insulin independence with A1c reduction below graft dysfunction criteria. Postprandial capillary blood glucose was significantly decreased (129.4+/-3.8 vs. 118.7+/-4.6 mg/dL; P<0.001), C-peptide and C-peptide-to-glucose ratio increased significantly by 5th and 6th months of treatment (ratio, 1.09+/-0.15 vs. 1.52+/-0.18; P<0.05). Weight loss more than 3 kg occurred in 8 of 12 (67%) subjects. Stimulation testing demonstrated improved glucose disposal and C-peptide secretion (glucose area under the curve 52,332+/-3,219 vs. 42,072+/-1,965; P=0.002 mg x min x dL, mixed meal stimulation index 0.50+/-0.06 vs. 0.66+/-0.09; P=0.03 pmol x mL), with marked suppression of glucagon secretion and progressive increase in amylin secretion. Side effects were more frequent and severe compared with published reports in type 2 diabetes, tolerated doses were lower.
CONCLUSIONS: Exenatide was tolerated in this patient population after appropriate dose titration and there appeared to be gradual but sustained positive effects on glycemic control and islet graft function.
METHODS: This prospective study evaluated the safety, efficacy, and metabolic effects of exenatide in subjects with type 1 diabetes mellitus and islet allograft dysfunction requiring exogenous insulin.
RESULTS: Sixteen subjects commenced exenatide, 12 continue (follow-up 214+/-57 days; range 108-287), four (25%) discontinued medication because of side effects. At 6 months, exogenous insulin was significantly reduced with stable glycemic control (0.15+/-0.02 vs. 0.11+/-0.025 U/kg per day; P<0.0001); three subjects discontinued insulin from 4, 5, and 9 U/day, respectively, two sustained insulin independence with A1c reduction below graft dysfunction criteria. Postprandial capillary blood glucose was significantly decreased (129.4+/-3.8 vs. 118.7+/-4.6 mg/dL; P<0.001), C-peptide and C-peptide-to-glucose ratio increased significantly by 5th and 6th months of treatment (ratio, 1.09+/-0.15 vs. 1.52+/-0.18; P<0.05). Weight loss more than 3 kg occurred in 8 of 12 (67%) subjects. Stimulation testing demonstrated improved glucose disposal and C-peptide secretion (glucose area under the curve 52,332+/-3,219 vs. 42,072+/-1,965; P=0.002 mg x min x dL, mixed meal stimulation index 0.50+/-0.06 vs. 0.66+/-0.09; P=0.03 pmol x mL), with marked suppression of glucagon secretion and progressive increase in amylin secretion. Side effects were more frequent and severe compared with published reports in type 2 diabetes, tolerated doses were lower.
CONCLUSIONS: Exenatide was tolerated in this patient population after appropriate dose titration and there appeared to be gradual but sustained positive effects on glycemic control and islet graft function.
Предметные рубрики MeSH
AdultAmyloidBlood GlucoseC-PeptideDiabetes Mellitus, Type 1ExenatideFeasibility StudiesGlucagonGraft RejectionGraft SurvivalHumansHypoglycemic AgentsImmunosuppressive AgentsInsulinIslet Amyloid PolypeptideIslets of Langerhans TransplantationMiddle AgedPeptidesProspective StudiesTime FactorsTransplantation, HomologousTreatment OutcomeVenoms