Oxidative stress and interleukin-6 secretion during the progression of type 1 diabetes.

OBJECTIVE: To evaluate inflammatory, oxidizing, and reducing responses during the progression of type 1 diabetes mellitus (T1DM) in patients without chronic complications. SUBJECTS AND METHODS: Plasma antioxidant status, reactive oxygen species (ROS), and interleukin-6 (IL-6) were measured in 42 patients with T1DM and in 24 healthy subjects. RESULTS: Significant increases were detected in the median values of ROS and IL-6 in patients with T1DM compared with healthy subjects (ROS ~ 4,836 vs. 2,036 RLU/min, respectively; P < .05: IL-6 ~ 14.2 vs. 9.7 pg/mL, respectively; P = .002). No significant between-group differences (P > 0.05) were observed in oxidizing responses or in IL-6 concentrations when diabetic patients were grouped according to time after diagnosis (0 - 10, 10 - 20 and > 20 years). Plasma antioxidant responses were similar in patients with T1DM and in healthy subjects. CONCLUSIONS: Our results demonstrate that oxidizing and inflammatory responses are increased at the onset of T1DM, but remain unchanged during disease progression. These findings suggest that functional changes involved in diabetic complications may commence in the first years after diagnosis.

Oxidative stress and interleukin-6 secretion during the progression of type 1 diabetes / Estresse oxidativo e secreção de interleucina-6 durante a progressão do diabetes tipo 1

OBJECTIVE: To evaluate inflammatory, oxidizing, and reducing responses during the progression of type 1 diabetes mellitus (T1DM) in patients without chronic complications. SUBJECTS AND METHODS: Plasma antioxidant status, reactive oxygen species (ROS), and interleukin-6 (IL-6) were measured in 42 patients with T1DM and in 24 healthy subjects. RESULTS: Significant increases were detected in the median values of ROS and IL-6 in patients with T1DM compared with healthy subjects (ROS ~ 4,836 vs. 2,036 RLU/min, respectively; P < .05: IL-6 ~ 14.2 vs. 9.7 pg/mL, respectively; P = .002). No significant between-group differences (P > 0.05) were observed in oxidizing responses or in IL-6 concentrations when diabetic patients were grouped according to time after diagnosis (0 - 10, 10 - 20 and > 20 years). Plasma antioxidant responses were similar in patients with T1DM and in healthy subjects. CONCLUSIONS: Our results demonstrate that oxidizing and inflammatory responses are increased at the onset of T1DM, but remain unchanged during disease progression. These findings suggest that functional changes involved in diabetic complications may commence in the first years after diagnosis.

OBJETIVO: Avaliar as respostas inflamatória, oxidativa e redutora na progressão do diabetes melito tipo 1 (DM1) em pacientes sem complicações crônicas. SUJEITOS E MÉTODOS: Capacidade antioxidante do plasma, espécies reativas de oxigênio (ROS) e interleucina-6 (IL-6) foram avaliadas em 42 pacientes com DM1 e 24 indivíduos saudáveis. RESULTADOS: Aumentos significativos foram detectados nas medianas de ROS e IL-6 em pacientes com DM1 comparados com indivíduos saudáveis (ROS ~ 4.836 vs. 2.036 RLU/min, respectivamente, P < 0,05: IL-6 ~ 14,2 vs. 9,7 pg/mL, respectivamente, P = 0,002). Diferenças não significativas (P > 0,05) foram observadas na resposta oxidante e IL-6 quando os diabéticos foram agrupados de acordo com o tempo após o diagnóstico (0-10, 10-20 e > 20 anos). A resposta antioxidante do plasma foi semelhante em pacientes com DM1 e em indivíduos saudáveis. CONCLUSÕES: Nossos resultados demonstram que as respostas oxidante e inflamatória estão aumentadas desde o início do DM1, mas mantêm-se inalteradas durante a progressão da doença, sugerindo que as mudanças funcionais envolvidas nas complicações diabéticas podem começar nos primeiros anos após o diagnóstico.

cAMP activates the generation of reactive oxygen species and inhibits the secretion of IL-6 in peripheral blood mononuclear cells from type 2 diabetic patients.

Peripheral blood mononuclear cells (PBMNC) from patients with type 2 diabetes (DM2) have generated higher levels of reactive oxygen species (ROS) that were higher than those in cells from healthy individuals. In the presence of a cAMP-elevating agent, ROS production was significantly activated in PBMNC from DM2 patients but it was inhibited in cells from healthy subjects. Higher levels of IL-6 has been detected in the supernatant of PBMNC cultures from DM2 patients in comparison with healthy controls. When cells were cultured in the presence of a cAMP-elevating agent, the level of IL-6 decreased has by 46% in the supernatant of PBMNC from DM2 patients but it remained unaltered in controls. No correlations between ROS and IL-6 levels in PBMNC from DM2 patients or controls have been observed. Secretions of IL-4 or IFNgamma by PBMNC from patients or controls have not been affected by the elevation of cAMP. cAMP elevating agents have activated the production of harmful reactive oxidant down modulated IL-6 secretion by these cells from DM2 patients, suggesting an alteration in the metabolic response possibly due to hyperglicemia. The results suggest that cAMP may play an important role in the pathogenesis of diabetes.