RESUMO
Diabetes mellitus (DM) is a chronic metabolic disease that may comorbid with various psychiatric disorders, such as anxiety and depression. The search for effective therapeutics to alleviate hyperglycemia and complications resulting from DM is continuous. Here we investigate the effects of diphenyl diselenide (DD), an organoselenium compound with several pharmacological properties, in a zebrafish model of hyperglycemia. Fish were fed for 74â¯days with a diet containing 3â¯mg/Kg DD, a concentration chosen after experiments based in a dose-response curve (DD 1, 2 and 3â¯mg/Kg) that did not cause overt toxicity (mortality, weight loss and neurobehavioral deficits). In the last 14â¯days of the experimental period, fish were concomitantly exposed to a glucose solution (111â¯mM). Afterwards, blood glucose levels, brain selenium (Se) content, and behavioral analysis aiming to assess anxiety-like behaviors and locomotor/exploratory activities were performed. In the novel tank diving test, glucose decreased vertical exploration and fish spent less time in the lit area when tested in the light-dark test, suggesting increased anxiety-like behavior. Moreover, DD decreased blood glucose levels in hyperglycemic fish as well as prevented the development of anxiety-related symptoms. DD diet alone did not change glycemia and behavioral parameters, but increased Se levels in the brain without affecting the cellular viability. Collectively, our findings highlight the growing utility of this zebrafish hyperglycemia model as a valuable strategy for further research in DM field and neuroprotective approaches.
Assuntos
Ansiedade/etiologia , Derivados de Benzeno/administração & dosagem , Hiperglicemia/complicações , Hiperglicemia/psicologia , Compostos Organosselênicos/administração & dosagem , Animais , Ansiedade/dietoterapia , Comportamento Animal/fisiologia , Glicemia/fisiologia , Encéfalo/metabolismo , Dieta , Modelos Animais de Doenças , Feminino , Glucose/administração & dosagem , Hiperglicemia/dietoterapia , Masculino , Selênio/metabolismo , Peixe-ZebraRESUMO
Anxiety and depression in diabetic patients contributes to a poor prognosis, but possible causal relationships have been controversial. Anxiety, fear, and anhedonia are mediated by interactions between different deep structures of the temporal lobe (e.g., amygdala complex and hippocampus) and other forebrain-related structures (e.g., lateral septal nucleus). Connections between these structures and the hypothalamic orexinergic system are necessary for the maintenance of energy and wakefulness. However, few studies have explored the impact of long-term hyperglycemia in these structures on anxiety. We induced long-term hyperglycemia (glucose levels of â¼500mg/dl) in Wistar rats by injecting them with alloxan and simultaneously protecting them from hyperglycemia by injecting them daily with a low dose of insulin (i.e., just enough insulin to avoid death), thus maintaining hyperglycemia and ketonuria for as long as 6 weeks. Compared with controls, long-term hyperglycemic rats exhibited a significant reduction of Fos expression in the lateral septal nucleus and basolateral amygdala, but no differences were found in cerebellar regions. Orexin-A cells appeared to be inactive in the lateral hypothalamus. No differences were found in sucrose consumption or behavior in the elevated plus maze compared with the control group, but a decrease in general locomotion was observed. These data indicate a generalized blunting of the metabolic brain response, accompanied by a decrease in locomotion but no changes in hedonic- or anxiety-like behavior.
Assuntos
Tonsila do Cerebelo/metabolismo , Hiperglicemia/metabolismo , Hipotálamo/metabolismo , Septo do Cérebro/metabolismo , Aloxano , Tonsila do Cerebelo/patologia , Anedonia , Animais , Ansiedade , Doença Crônica , Sacarose Alimentar , Modelos Animais de Doenças , Hiperglicemia/patologia , Hiperglicemia/psicologia , Hipotálamo/patologia , Imuno-Histoquímica , Cetose/metabolismo , Cetose/patologia , Cetose/psicologia , Masculino , Atividade Motora/fisiologia , Orexinas/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Wistar , Septo do Cérebro/patologiaRESUMO
INTRODUCTION: A number of physical and psychological changes that occur during pregnancy can stimulate the development of psychological disorders such as anxiety and depression. The study evaluated psychological aspects related to maternal depression and anxiety in pregnant women with diabetes mellitus or hyperglycemia, contrasting the results with those of non-diabetic pregnant women. METHOD: In a prospective and longitudinal approach, two questionnaires were applied and validated for use in Brazil, the Beck depression inventory and the State-Trait Anxiety Inventory. The questionnaires were applied to pregnant women at the first prenatal visit or at the time of disease diagnosis (T1) and reapplied at admission for delivery (T2). Regardless of the degree of hyperglycemia, both at first and in the second stage most women had severe anxiety trait. In early pregnancy (T1), however, severe state anxiety was more frequent in women with hyperglycemia than in those from the NG group. RESULTS: Most pregnant women showed moderate state anxiety over their pregnancy, regardless of glycemic status. In early pregnancy, however, severe state anxiety was more prevalent in hyperglycemic women than in those with normal glycemic status. Most women showed moderate trait anxiety and mild depression in both early and late pregnancy, irrespective of glycemic status. CONCLUSION: The incidence of severe state anxiety in early pregnancy is more frequent in women with diabetes or hyperglycemia, but their levels of trait anxiety and depression are not affected by glycemic status.
Assuntos
Ansiedade/epidemiologia , Depressão/diagnóstico , Diabetes Mellitus/psicologia , Hiperglicemia/diagnóstico , Gravidez em Diabéticas/psicologia , Gestantes/psicologia , Adulto , Ansiedade/diagnóstico , Ansiedade/psicologia , Brasil/epidemiologia , Depressão/epidemiologia , Diabetes Mellitus/sangue , Diabetes Mellitus/epidemiologia , Feminino , Humanos , Hiperglicemia/psicologia , Incidência , Gravidez , Gravidez em Diabéticas/sangue , Cuidado Pré-Natal/métodos , Prevalência , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Inquéritos e QuestionáriosRESUMO
Diabetes is a chronic and progressive syndrome commonly associated with several neuropsychiatric comorbities, of which depression is the most studied. The prevalence of depression is about two or three times higher in diabetic patients compared to the general population. It is believed that the diabetes - depression relation may be bidirectional, i.e., the depression can lead to diabetes and conversely diabetes could facilitate the emergence of depression. Depression is one of the most neglected symptoms in diabetic patients and is directly linked with lowering of quality of life. The treatment of depression in these patients is still quite ineffective and in many cases treatmentrefractory. Furthermore, some of the first choice drugs used to treat the depression affect the blood glucose control, aggravating the hyperglycemic state. These issues underscore the urgency in studies searching for new pharmacological targets for the treatment of depression associated with diabetes. For this, a better understanding of the pathophysiology that relates this comorbidity becomes critical. In this respect, this review will focus on some hypotheses that have been proposed to explain the mechanisms underlying depression associated with diabetes, highlighting the treatment options currently available and their limitations. Among these hypotheses, we will point out the hyperglycemia as a primary metabolic cause of the depression development, the involvement of the dysregulation of hypothalamic pituitary-adrenal (HPA) axis and of neurotransmitter systems, specially monoaminergic system. Besides, the role of oxidative stress, neuroinflammation and cell death, especially in hippocampus and prefrontal cortex, brain areas important for the mediation and modulation of emotional behavior will also be discussed. Finally, we will bring up the influence of the epigenetic regulation with respect to neuropsychiatric disorders.
Assuntos
Depressão/etiologia , Depressão/terapia , Diabetes Mellitus/psicologia , Diabetes Mellitus/terapia , Comorbidade , Depressão/epidemiologia , Complicações do Diabetes/psicologia , Complicações do Diabetes/terapia , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/fisiopatologia , Humanos , Hiperglicemia/complicações , Hiperglicemia/fisiopatologia , Hiperglicemia/psicologia , Sistema Hipotálamo-Hipofisário/fisiopatologia , Sistema Hipófise-Suprarrenal/fisiopatologiaRESUMO
BACKGROUND: Stress hyperglycemia is the elevation of serum glucose found in a patient, once he is admitted in the hospital. The objective of this study was to evaluate the impact of admission serum glucose level in the outcome of noncritical hospitalized patients. METHODS: A prospective analytical cohort study was conducted in patients hospitalized in the Internal Medicine service of the Hospital de Especialidades, Centro Médico Nacional Siglo XXI (Instituto Mexicano del Seguro Social), from September 2011 to February 2012. RESULTS: We included 89 patients with serum glucose level < 110 mg/dL (group A) and 90 patients with serum glucose > 110 mg/dL (group B). Diabetes mellitus was more frequent in group B (p < 0.001). Glycosylated hemoglobin greater than 6.5 % was found in 36.4 % of the patients in group B and in 8.7 % in group A (p < 0.001). Patients in group B had higher APACHE II score (p = 0.02) and worse in-hospital outcomes. CONCLUSIONS: Stress hyperglycemia was associated with higher APACHE II score and more medical complications, such as sepsis, urinary tract infection, pneumonia and use of pressor amines. Mortality independent predictors were systemic arterial hypertension and APACHE II score.
Introducción: la hiperglucemia de estrés es la elevación de la glucosa sérica que se encuentra a la admisión hospitalaria de un paciente. El objetivo fue evaluar el impacto de la hiperglucemia de estrés al ingreso en el desenlace de pacientes no críticos hospitalizados en un servicio de Medicina Interna. Métodos: estudio de cohorte prospectivo y analítico realizado en pacientes de Medicina Interna del Hospital de Especialidades del Centro Médico Nacional Siglo XXI del Instituto Mexicano del Seguro Social, de septiembre de 2011 a febrero de 2012. Resultados: se incluyeron 89 pacientes con niveles séricos de glucosa < 110 mg/dL (grupo A) y 90 pacientes con niveles de glucosa > 110 mg/dL (grupo B). La diabetes mellitus fue más frecuente en el grupo B (p < 0.001). La hemoglobina glucosilada mayor a 6.5 % se encontró en el 36.4 % de los pacientes del grupo B y en el 8.7 % del grupo A, (p < 0.001). Los pacientes del grupo B tuvieron mayor puntuación en el APACHE II (p = 0.02) y tendencia a mayor frecuencia de complicaciones. Conclusiones: la hiperglucemia de estrés se asocia a una mayor puntuación de APACHE II, y tiende a una mayor frecuencia de enfermedad crítica, sepsis, infección de vías urinarias, neumonía y uso de aminas vasopresoras. Los predictores independientes de muerte fueron la presencia de hipertensión arterial y el score APACHE II.
Assuntos
Infecção Hospitalar/etiologia , Hospitalização , Hiperglicemia/complicações , Hiperglicemia/psicologia , Estresse Psicológico/complicações , APACHE , Adulto , Idoso , Estudos de Casos e Controles , Infecção Hospitalar/epidemiologia , Feminino , Humanos , Hiperglicemia/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
The aim of the present study was to evaluate the effect of maternal mild hyperglycemia on maternal behavior, as well as the development, behavior, reproductive function, and glucose tolerance of the offspring. At birth, litters were assigned either to Control (subcutaneous (sc)-citrate buffer) or STZ groups (streptozotocin (STZ)-100mg/kg-sc.). On PND 90 both STZ-treated and Control female rats were mated. Glucose tolerance tests (GTT) and insulin tolerance tests (ITT) were performed during pregnancy. Pregnancy duration, litter size and sex ratio were assessed. Newborns were classified according to birth weight as small (SPA), adequate (APA), or large for pregnancy age (LPA). Maternal behavior was analyzed on PND 5 and 10. Offspring body weight, length, and anogenital distance were measured and general activity was assessed in the open field. Sexual behavior was tested in both male and female offspring. Levels of reproductive hormones and estrous cycle duration were evaluated in female offspring. Female offspring were mated and both a GTT and ITT performed during pregnancy. Neonatal STZ administration caused mild hyperglycemia during pregnancy and changed some aspects of maternal care. The hyperglycemic intrauterine milieu impaired physical development and increased immobility in the open field in the offspring although the latter effect appeared at different ages for males (adulthood) and females (infancy). There was no impairment in the sexual behavior of either male or female offspring. As adults, female offspring of STZ-treated mothers did not show glucose intolerance during pregnancy. Thus, offspring of female rats that show mild hyperglycemia in pregnancy have fewer behavioral and developmental impairments than previously reported in the offspring of severely diabetic dams suggesting that the degree of impairment is directly related to the mother glycemic intensity.
Assuntos
Animais Recém-Nascidos/crescimento & desenvolvimento , Comportamento Animal/fisiologia , Hiperglicemia/psicologia , Comportamento Materno , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Efeitos Tardios da Exposição Pré-Natal/psicologia , Fatores Etários , Análise de Variância , Animais , Peso ao Nascer , Glicemia , Peso Corporal , Comportamento Exploratório , Feminino , Teste de Tolerância a Glucose , Hiperglicemia/induzido quimicamente , Insulina/sangue , Tamanho da Ninhada de Vivíparos , Masculino , Gravidez , Ratos , Ratos Wistar , Caracteres Sexuais , Razão de Masculinidade , Desenvolvimento Sexual , Estreptozocina/toxicidadeRESUMO
BACKGROUND: Quality of life decreases after the menopause as it has been assessed by several designed tools. Despite this, few studies have reported correlations between quality of life and the metabolic syndrome and its determinants. OBJECTIVE: Evaluate quality of life and determine factors related to its impairment among postmenopausal Ecuadorian women. METHODS: Postmenopausal women that participated in a metabolic syndrome screening and educational program at the Institute of Biomedicine of the Universidad Católica of Guayaquil, Ecuador were interviewed using the Menopause-Specific Quality of Life Questionnaire (MENQOL). Mean domain scores as well as factors associated to higher scores within each of the domains of the questionnaire (vasomotor, psycho-social, physical and sexual) were determined. RESULTS: Three hundred twenty-five postmenopausal women (n=325) were surveyed. Mean age of participants was 55.9+/-8.1 years (median: 54 years). Women presented metabolic syndrome, hypertension, hyperglycemia, hypertriglyceridemia and abdominal obesity in 41.5%, 38.8%, 16.6%, 56.9% and 54.2% respectively. Mean scores obtained for each domain were: vasomotor: 3.5+/-2.5 (median 3); psycho-social: 3.7+/-1.5 (median 3.6); physical: 3.8+/-1.2 (median 3.8); sexual: 4.9+/-2.3 (median 5.3). More than 50% of women had scores above the median for each domain of the questionnaire. Logistic regression determined that vasomotor score decreased with age. Abdominal obesity increased the risk of having vasomotor, psycho-social and physical scores above the median. Hypertension and hyperglycemia increased the risk for higher scores within the psycho-social and sexual domain respectively. CONCLUSION: In this postmenopausal Ecuadorian population, impairment of quality of life was found to be associated to age and related conditions such as abdominal obesity, hypertension and hyperglycemia.
Assuntos
Síndrome Metabólica/psicologia , Pós-Menopausa/psicologia , Qualidade de Vida/psicologia , Adulto , Fatores Etários , Idoso , Equador/etnologia , Feminino , Nível de Saúde , Humanos , Hiperglicemia/psicologia , Hipertensão/psicologia , Programas de Rastreamento , Síndrome Metabólica/complicações , Síndrome Metabólica/etnologia , Pessoa de Meia-Idade , Obesidade/psicologia , Pós-Menopausa/etnologiaRESUMO
OBJECTIVE: To determine whether acute hyperglycemia adversely affects mental efficiency to the same extent as acute mild hypoglycemia. STUDY DESIGN: We administered a battery of cognitive tests to adolescents studied at hyperglycemic (20 mmol/L (360 mg/dl)), hypoglycemic (3.3 mmol/L (60 mg/dl)), or euglycemic (5.5 mmol/L (100 mg/dl)) targets, which were maintained by an insulin-glucose clamp. The study included 36 children, 9 to 19 years of age (mean = 14.7 years), with diabetes duration more than 2 years (mean = 6.9 years). RESULTS: Cognitive test performance did not deteriorate during hyperglycemia. In contrast, there was a significant decline in performance on all cognitive tests during mild hypoglycemia. Autonomic symptoms did not change significantly during hyperglycemia or during the rapid return from hyperglycemia to euglycemia. Although significant increments in epinephrine and pancreatic polypeptide levels occurred during mild hypoglycemia, no changes in counterregulatory hormones occurred during hyperglycemia. An exploratory regression analysis demonstrated that changes in mental efficiency were best predicted by increases in pancreatic polypeptide, a marker of autonomic activation. CONCLUSION: These results confirm our previous finding that mild hypoglycemia causes transient decrements in cognitive function. In contrast, neither hyperglycemia, nor the rapid drop from acute hyperglycemia to euglycemia, affected symptoms, cognitive function, or counterregulatory hormone secretion.