RESUMEN
Pancreatic ß cell apoptosis is important in the pathogenesis of type 2 diabetes mellitus (T2DM). Generally, apoptotic ß cells are phagocytosed by macrophages in a process known as "efferocytosis." Efferocytosis is critical to the resolution of inflammation and is impaired in T2DM. Advanced glycation end products (AGEs), which are increased in T2DM, are known to suppress phagocytosis function in macrophages. In this study, we found that AGEs inhibited efferocytosis of apoptotic ß cells by primary peritoneal macrophages in C57BL/6J mice or mouse macrophage cell line Raw264.7. Mechanistically, AGEs inhibit efferocytosis by blocking Ras-related C3 botulinum toxin substrate 1 activity and cytoskeletal rearrangement through receptor for advanced glycation end products/ras homolog family member A/Rho kinase signaling in macrophages. Furthermore, it was observed that AGEs decreased the secretion of anti-inflammatory factors and promoted the proinflammatory ones to modulate the inflammation function of efferocytosis. Taken together, our results indicate that AGEs inhibit efferocytosis through binding to receptor for advanced glycation end products and activating ras homolog family member A/Rho kinase signaling, thereby inhibiting the anti-inflammatory function of efferocytosis.
Asunto(s)
Diabetes Mellitus Tipo 2/patología , Productos Finales de Glicación Avanzada/metabolismo , Células Secretoras de Insulina/metabolismo , Macrófagos Peritoneales/inmunología , Fagocitosis/fisiología , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Animales , Apoptosis/fisiología , Toxinas Botulínicas/metabolismo , Línea Celular , Humanos , Inflamación/patología , Masculino , Ratones , Ratones Endogámicos C57BL , Células RAW 264.7 , Transducción de Señal/fisiología , Quinasas Asociadas a rho/metabolismo , Proteína de Unión al GTP rhoA/metabolismoRESUMEN
OBJECTIVE: Atherosclerosis is considered a chronic inflammatory condition. The immune system is a key mediator in the initiation and progression of atherosclerosis. In a previous study, we found that the immune system was activated in diabetes and that total white blood cell (WBC) counts were elevated significantly in diabetic patients. To investigate whether WBC subtype counts in newly diagnosed diabetes are risk factors for future cardiovascular disease (CVD) events, we conducted a prospective population-based cohort study. METHODS: A total of 1498 newly diagnosed diabetic patients aged 40 to 70 years old were followed up for three years. Participants with previous CVD history and abnormal WBC counts were excluded. CVD events were recorded during follow-up. RESULTS: We found that the baseline lymphocyte counts were independently associated with cardiovascular events during follow-up, with the Exp (ß) (95% CI) at 1.749 (1.084-2.821). Lymphocyte count ≥2.9 (109/L) was significantly associated with the development of CVD (HR, 2.29; 95% CI, 1.12-4.67). The corresponding incidence of CVD per 1000 person-year for the lymphocyte count ≤2.8 (109/L) and lymphocyte count ≥2.9 (109/L) groups were 11.26 and 26.38, respectively. CONCLUSION: We concluded that even in a normal range, higher lymphocyte levels may result in a significantly higher CVD risk among diabetic patients. Lymphocyte count ≥2.9 (109/L) is an independent predictor of developing future CVD events.
Asunto(s)
Aterosclerosis , Enfermedades Cardiovasculares , Diabetes Mellitus , Adulto , Anciano , Aterosclerosis/diagnóstico , Aterosclerosis/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Estudios de Cohortes , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiología , Humanos , Linfocitos , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
The present analysis aims to investigate the prevalence of thyroid nodules in type 2 diabetes mellitus (T2DM) population. We searched PubMed, EMBASE, and Web of Science from inception to the March 1, 2018. The studies were selected to estimate the prevalence of thyroid nodules in T2DM subjects and to compare the prevalence of thyroid nodules in different glucose tolerance status. The random effects model was used, and the outcome was presented as a pooled prevalence proportion with 95% confidence interval (95% CI) or a summary odds ratio (OR) with 95% CI. In the end, 9 studies met the inclusion criteria and were included in the analysis. The pooled prevalence of thyroid nodules was 60% (95% CI: 0.52, 0.68) for T2DM 2 diabetes patients, 50% (95% CI: 0.48, 0.51) for pre-diabetes, and 43% (95% CI: 0.34, 0.52) for normal glucose tolerance population. Compared with patients without diabetes, diabetes subjects are more likely to develop thyroid nodules, adjusted OR for thyroid nodule was 1.78 (95% CI: 1.25, 2.55). Insulin resistance might be involved in thyroid nodule development.