RESUMO
Islet transplantation is an experimental therapy for selected patients with type 1 diabetes (T1DM). It remains limited by immunosuppressive drug toxicity, progressive loss of insulin independence, allosensitization and the need for multiple islet donors. We describe our experience with an efalizumab-based immunosuppressive regimen as compared to the prevailing standard regimen, the Edmonton protocol. Twelve patients with T1DM received islet transplants: eight were treated with the Edmonton protocol; four were treated with daclizumab induction, a 6-month course of tacrolimus, and maintenance with efalizumab and mycophenolate mofetil. The primary endpoint was insulin independence after one islet infusion. Only two Edmonton protocol treated patients achieved the primary endpoint; six required islets from multiple donors, and all experienced leukopenia, mouth ulcers, anemia, diarrhea and hypertransaminasemia. Four became allosensitized. All patients treated with the efalizumab-based regimen achieved insulin independence with normal hemoglobin A1c after a single islet cell infusion and remained insulin independent while on efalizumab. These patients experienced significantly fewer side effects and none became allosensitized. Trial continuation was terminated by withdrawal of efalizumab from the market. These data suggest that this efalizumab-based regimen prevents islet rejection, is well tolerated, and allows for single donor islet transplantation.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/cirurgia , Rejeição de Enxerto/prevenção & controle , Imunossupressores/uso terapêutico , Transplante das Ilhotas Pancreáticas/efeitos adversos , Doadores de Tecidos , Adulto , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Daclizumabe , Diabetes Mellitus Tipo 1/metabolismo , Estudos de Viabilidade , Humanos , Imunoglobulina G/efeitos adversos , Imunoglobulina G/uso terapêutico , Imunossupressores/efeitos adversos , Insulina/metabolismo , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Resultado do TratamentoRESUMO
Low levels of high-density lipoprotein cholesterol (HDL-C) constitute a strong risk factor for developing coronary heart disease. This risk can be decreased by even slight improvements in HDL-C levels. This review discusses both pharmacologic and nonpharmacologic treatments of patients with low levels of HDL-C, including lifestyle modifications and the benefits of oral estrogens, niacin, fibrates, statins, and combination drug therapy.