RESUMEN
AIMS: To examine the association between diabetes duration and hypoglycaemia symptom profiles and the presence of impaired awareness of hypoglycaemia. METHODS: A cross-sectional study was performed, using validated methods for recording hypoglycaemia symptoms and assessing hypoglycaemia awareness. The associations between symptom intensity, hypoglycaemia awareness and diabetes duration were examined, and the prevalence of impaired awareness was ascertained for Type 1 diabetes of differing durations. RESULTS: Questionnaires were mailed to 636 adults with Type 1 diabetes, of whom 445 (70%) returned them. A total of 440 completed questionnaires were suitable for analysis. Longer diabetes duration was associated with lower intensity of autonomic symptoms (P for trend <0.001), but no association was observed with neuroglycopenic symptoms. The overall prevalence of impaired awareness of hypoglycaemia in this cohort was 17% (95% CI 14-21%) and increased with diabetes duration, from 3% for duration 2-9 years to 28% for duration ≥30 years (P for trend <0.001). Low autonomic symptom scores were not associated with a higher prevalence of impaired awareness. CONCLUSIONS: Longer diabetes duration was associated with lower intensity of autonomic symptoms and a higher prevalence of impaired awareness of hypoglycaemia, suggesting that subjective symptoms of hypoglycaemia change over time. These observations underline the need for regular patient education about hypoglycaemia symptomatology and clinical screening for impaired awareness of hypoglycaemia.
Asunto(s)
Vías Autónomas/efectos de los fármacos , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Retroalimentación Fisiológica , Hipoglucemia/diagnóstico , Hipoglucemiantes/efectos adversos , Insulina/efectos adversos , Autocuidado , Adolescente , Adulto , Anciano , Actitud Frente a la Salud , Vías Autónomas/fisiopatología , Estudios de Cohortes , Estudios Transversales , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/fisiopatología , Progresión de la Enfermedad , Retroalimentación Fisiológica/efectos de los fármacos , Femenino , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/fisiopatología , Hipoglucemia/prevención & control , Hipoglucemiantes/uso terapéutico , Insulina/uso terapéutico , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Adulto JovenRESUMEN
The purpose of this study was to explore whether bilateral frontal cortex contusion in rats would demonstrate changes relevant for understanding the pathology of frontal lobe injury in humans. Rats were allowed to survive for 3, 7, or 18 days postinjury (dpi). In the contused rats, albumin was trapped in frontal cortices, as well as in other brain areas, showing that neurons were exposed to plasma components. In the sham-operated rats, which had only craniotomy but no penetration of dura, the level of trapped albumin was also increased compared to intact controls, suggesting a partial lesion-like condition. Choline acetyltransferase activity was severely decreased in the frontal cortices of contused rats, compared to the sham-operated controls. The decrease was most pronounced at 3 dpi and less pronounced 18 dpi, suggesting that after the initial damage, regeneration of the cholinergic terminals occurred. The concentration of the mature presynaptic membrane protein D3(SNAP-25) was also decreased in the frontal cortices of contused rats at 3 and 7 dpi, whereas it was normalized at 18 dpi. Previously, we have evaluated changes in the rate of synaptic remodeling in brain injury by calculating the ratio of the neural cell adhesion molecule (NCAM) to D3(SNAP-25). The NCAM/D3(SNAP-25) ratio at 3 dpi was elevated by more than 60% in the frontal cortices of contused rats, suggesting a high initial rate of synaptic remodeling. The ratios were smaller at 7 and 18 dpi, suggesting that after the initial burst, the rate of remodeling leveled off. In contrast, astrocyte activation was less pronounced at 3 dpi than at 7 and 18 dpi, as measured by the levels of glial fibrillary acidic protein and glutamine synthetase immunoactivities. The immunoreactivity of glutamine synthetase more than doubled in the contused brains but its enzymatic activity increased less than 50%, suggesting that many enzymatic centers had been inactivated by free radicals. Calculated as the difference between the relative immunoreactivity and the relative enzymatic activity the "lost glutamine synthetase activity" increased continuously in frontal cortex and striatum from 3 to 18 dpi, indicating the production of free radicals long after the initial contusion event. In conclusion, following frontal cortical contusions the early synaptic damage was partly compensated by synaptic remodeling. We suggest that the continuous production of free radicals may have contributed to the declining remodeling rate and impair functional recovery.