RESUMO
Inflammation at the level of the ß cell appears to be involved in progressive ß-cell dysfunction in type 2 diabetes. We assessed the effect of blocking interleukin-1 (IL-1) by anakinra [recombinant human interleukin-1 receptor antagonist (IL-1Ra)] on ß-cell function. Sixteen participants with impaired glucose tolerance were treated with 150 mg anakinra daily for 4 weeks in a double blind, randomized, placebo-controlled cross-over study with a wash-out period of 4 weeks. At the end of each treatment period, oral glucose tolerance tests (OGTTs) and hyperglycaemic clamps were performed. First-phase insulin secretion improved after anakinra treatment compared with placebo, 148 ± 20 versus 123 ± 14 mU/l, respectively (p = 0.03), and the insulinogenic index was higher after anakinra treatment. These results support the concept of involvement of IL-1ß in the (progressive) decrease of insulin secretion capacity associated with type 2 diabetes.
Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Intolerância à Glucose/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Células Secretoras de Insulina/efeitos dos fármacos , Insulina/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Receptores de Interleucina-1/antagonistas & inibidores , Estudos Cross-Over , Diabetes Mellitus Tipo 2/sangue , Método Duplo-Cego , Feminino , Intolerância à Glucose/sangue , Teste de Tolerância a Glucose , Humanos , Hipoglicemiantes/administração & dosagem , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Proteína Antagonista do Receptor de Interleucina 1/administração & dosagem , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
3 female patients who were being treated with methotrexate developed a non-Hodgkin lymphoma. The first patient, 67 years old, presented with an enlarged thyroid gland. The cytological punction was inconclusive and an open biopsy revealed a B cell non-Hodgkin lymphoma, which was localised. A week before the biopsy the methotrexate was discontinued. The patient herself reported that the swelling of her thyroid gland was diminished after cessation of methotrexate. The lymphoma showed a complete remission without chemotherapy being given. The second patient, a 78-year-old woman, developed a non-Hodgkin lymphoma in one of her tonsils that showed a partial remission after withdrawal of the methotrexate therapy. The third patient, a 66-year-old woman, presented herself with a pulmonary non-Hodgkin lymphoma. In this patient withdrawal of the methotrexate resulted in a complete remission of the non-Hodgkin lymphoma as well. Although no epidemiological study has shown an increased risk of lymphoproliferative disorders during the use of methotrexate, these spontaneous remissions suggest an aetiological link. If a non-Hodgkin lymphoma develops in a patient being treated with methotrexate then the therapy should be discontinued and chemotherapy should not be given straightaway.
Assuntos
Antirreumáticos/efeitos adversos , Linfoma não Hodgkin/induzido quimicamente , Metotrexato/efeitos adversos , Idoso , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Feminino , Humanos , Metotrexato/uso terapêutico , Remissão EspontâneaRESUMO
AIMS: The enzyme dipeptidyl peptidase-4 (DPP-4) is a key player in the degradation of incretin hormones that are involved in glucose metabolism. DPP-4 is also expressed on immune cells and is associated with several immunological functions. Some studies have reported increased rates of infections in patients treated with DPP-4 inhibitors. We therefore assessed whether treatment with the DPP-4 inhibitor vildagliptin affected cytokine production and T-cell differentiation. METHODS: Patients with type 2 diabetes were treated with vildagliptin or an active comparator, acarbose, for four weeks, in a randomized cross-over trial. Blood was sampled at the end of each treatment period and peripheral blood mononuclear cells were isolated and stimulated with a broad spectrum of pattern recognition receptor agonists. RESULTS: Serum cytokine concentrations and ex vivo cytokine production (both monocyte and T-cell derived) did not differ during treatment with vildagliptin compared to acarbose. Similarly, ex vivo relative upregulation of mRNA transcription of T-cell lineage specific transcription factors was unaffected by vildagliptin treatment. CONCLUSIONS: These data show that a four-week treatment with vildagliptin in patients with type 2 diabetes mellitus does not result in a significant modulation of cytokine responses. This observation suggests that inhibition of DDP-4 does not lead to an increased risk of infection by diminishing cytokine production.