RESUMO
Antecedentes: Diabetes Mellitus (DM) se consi- dera una enfermedad metabólica con hiperglu- cemia de forma crónica, causada por un déficit parcial o total en la secreción o acción de la in- sulina. El 70-90% de DM1 tienen base autoin- mune. Objetivo: Describir las características clí- nico- epidemiológicas de Diabetes Mellitus I en Pediatría del Hospital Mario Catarino Rivas, San Pedro Sula, Cortés, en el período comprendido entre junio de 2017 - junio de 2019. Pacientes y métodos: Estudio cuantitativo, descriptivo, observacional, realizado en pacientes menores de 18 años que reunieron criterios de inclusión. Los datos se recolectaron mediante encuesta. Re- sultados: El grupo de edad más frecuente fue el escolar de 6-12 años en 49%. Mas frecuente en mujeres en 51%, 29% de los pacientes estudiados presentaron sedentarismo, 17% dislipidemias y sobrepeso, diagnosticadas en el debut de la enfer- medad. Los síntomas más frecuentes fueron po- lifagia en 44%, poliuria en 21%. Conclusiones: Las características socio-demográficas del grupo poblacional estudiado fueron las siguientes, el sexo más afectado fue el femenino y el grupo de edad más frecuente los escolares que se encuen- tran cursando la primaria, la mayoría de los pa- cientes estudiados no presentaban enfermedades asociadas, mientras que solo unos pocos presen- taban sobrepeso y dislipidemias asociado a Dia- betes Mellitus tipo I, se observó un predominio del debut sintomático asociado con la triada de polifagia, polidipsia y poliuria, además visión borrosa y pérdida de peso...(AU)
Assuntos
Humanos , Masculino , Feminino , Criança , Diabetes Mellitus Tipo 1/epidemiologia , Insulina/deficiência , Dislipidemias , Obesidade Infantil/complicaçõesRESUMO
BACKGROUND: Certain HLA class II haplotypes have long been related with the risk of developing type 1 diabetes. The presence of the HLA haplotype DRB1*04/DQA1*03/DQB1*03:02, together with specific ß-cell autoantibodies, contributes to the development and/or severity of insulin deficiency in type 1 diabetes. OBJECTIVE: To evaluate the association of HLA risk haplotype HLA-DRB1/-DQA1/-DQB1 with ß-cell function and antibody markers in recent-onset type 1 diabetes patients, their siblings, and controls. METHODS: We studied recently diagnosed type 1 diabetes pediatric patients, their siblings, and healthy controls, analyzing autoantibodies (anti-glutamic acid decarboxylase, anti-IA-2, and anti-insulin), HLA risk and protector haplotypes, and ß-cell function (plasma proinsulin, insulin and C-peptide). X2, ANOVA or Kruskal-Wallis and multiple logistic regression were used to analyze data. RESULTS: We included 46 patients, 72 siblings, and 160 controls. Prevalence of anti-tyrosine phosphatase-related islet antigen 2 and anti-glutamic acid decarboxylase antibodies was higher in patients than siblings and controls. We found risk haplotype DRB1*04/DQA1*03/DQB1*03:02 in 95.7% of patients vs. 51.87% of controls; DRB1*03:01/DQA1*05/DQB1*02 in 47.8% of patients vs. 8.12% of controls; and DRB1*14/DQA1*05/DQB1*03:01 in 2.2% of patients vs. 20.0% of controls. With DRB1*04/DQA1*03/DQB1*03:02, the prevalence of antibodies was significantly higher in patients, although not within any single group. In regression model based on insulin secretion, only anti-tyrosine phosphatase-related islet antigen 2 antibodies and age were associated with the risk haplotype. CONCLUSIONS: The DRB1*04/DQA1*03/DQB1*03:02 haplotype increased the risk for lower insulin, proinsulin, and C-peptide concentrations, suggesting an association with the severity of insulin deficiency in type 1 diabetes patients. This haplotype, added to antibody positivity, is a predictor of deficient insulin secretion in a Mexican pediatric population.
Assuntos
Autoanticorpos/imunologia , Diabetes Mellitus Tipo 1/genética , Antígenos HLA-D/genética , Insulina/metabolismo , Adolescente , Adulto , Criança , Pré-Escolar , Estudos Transversais , Diabetes Mellitus Tipo 1/imunologia , Feminino , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Haplótipos , Humanos , Insulina/deficiência , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Modelos Logísticos , Masculino , México , Risco , Adulto JovemRESUMO
Type 1 diabetes mellitus (T1DM) is associated with chronic systemic inflammation and enhanced susceptibility to systemic bacterial infection (sepsis). We hypothesized that low insulin concentrations in T1DM trigger the enzyme 5-lipoxygenase (5-LO) to produce the lipid mediator leukotriene B4 (LTB4), which triggers systemic inflammation that may increase susceptibility to polymicrobial sepsis. Consistent with chronic inflammation, peritoneal macrophages from two mouse models of T1DM had greater abundance of the adaptor MyD88 (myeloid differentiation factor 88) and its direct transcriptional effector STAT-1 (signal transducer and activator of transcription 1) than macrophages from nondiabetic mice. Expression of Alox5, which encodes 5-LO, and the concentration of the proinflammatory cytokine interleukin-1ß (IL-1ß) were also increased in peritoneal macrophages and serum from T1DM mice. Insulin treatment reduced LTB4 concentrations in the circulation and Myd88 and Stat1 expression in the macrophages from T1DM mice. T1DM mice treated with a 5-LO inhibitor had reduced Myd88 mRNA in macrophages and increased abundance of IL-1 receptor antagonist and reduced production of IL-ß in the circulation. T1DM mice lacking 5-LO or the receptor for LTB4 also produced less proinflammatory cytokines. Compared to wild-type or untreated diabetic mice, T1DM mice lacking the receptor for LTB4 or treated with a 5-LO inhibitor survived polymicrobial sepsis, had reduced production of proinflammatory cytokines, and had decreased bacterial counts. These results uncover a role for LTB4 in promoting sterile inflammation in diabetes and the enhanced susceptibility to sepsis in T1DM.
Assuntos
Diabetes Mellitus Tipo 1/complicações , Regulação da Expressão Gênica/fisiologia , Mediadores da Inflamação/metabolismo , Inflamação/complicações , Leucotrieno B4/metabolismo , Sepse/etiologia , Análise de Variância , Animais , Araquidonato 5-Lipoxigenase/genética , Araquidonato 5-Lipoxigenase/metabolismo , Imunoprecipitação da Cromatina , Citocinas/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Immunoblotting , Inflamação/metabolismo , Insulina/deficiência , Insulina/farmacologia , Macrófagos/metabolismo , Camundongos , Camundongos Knockout , Fator 88 de Diferenciação Mieloide/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Transcrição STAT1/metabolismo , Sepse/metabolismoRESUMO
La diabetes mellitus (DBT) es un desorden metabólico producto de una deficiencia absoluta o relativa de insulina. Este trastorno tiene consecuencias de importancia en varios órganos y sistemas del cuerpo. Es bien conocido que la DBT está asociada con una cantidad de manifestaciones cutáneas y osteoarticulares. La más común de estas características afecta al pie (síndrome de pie diabético); sin embargo, similares lesiones se pueden observar en la mano (síndrome de mano diabética), generalmente asociadas a una larga evolución de la enfermedad, malos controles glicémicos y complicaciones microvasculares. En este artículo se realiza una revisión de la literatura para actualizar el diagnóstico y la terapéutica de manifestaciones musculo-esqueléticas en la mano de pacientes con DBT: movilidad articular limitada, contractura de Dupuytren, tenosinovitis del flexor (dedo en gatillo), infección por síndrome de mano diabética tropical, ulceración neuropática periférica, síndrome del túnel carpiano, neuropatía cubital y neuropatía en piel y uñas.
Diabetes mellitus (DBT) is a metabolic disorder caused by absolute or relative deficiency of insulin. This disorder has importance consequences in various organs and systems. It is well known that DBT is associated with cutaneous and osteoarticular manifestations; the most common of these complications affects the foot (diabetic foot syndrome). However, similar lesions can be observed in the hand (diabetic hand syndrome), usually associated with long standing disease, poor glycemic control and microvascular complications. This article makes a review of the literature to update diagnosis and therapy ofmusculoskeletal manifestations in patients with diabetic hand syndrome: limited joint mobility, Dupuytrens contracture, trigger finger, tropical diabetic hand, peripheral neuropathic ulceration, carpal tunnel syndrome, cubital neuropathy, and skin and nail changes.
Assuntos
Humanos , Complicações do Diabetes/complicações , Contratura de Dupuytren/etiologia , Diabetes Mellitus/etiologia , Insulina/deficiência , Limitação da Mobilidade , Neuropatias Ulnares/etiologia , Neuropatias Diabéticas/etiologia , Síndrome do Túnel Carpal/etiologia , Tenossinovite/etiologia , Transtornos do Metabolismo de Glucose/diagnósticoRESUMO
La diabetes mellitus (DBT) es un desorden metabólico producto de una deficiencia absoluta o relativa de insulina. Este trastorno tiene consecuencias de importancia en varios órganos y sistemas del cuerpo. Es bien conocido que la DBT está asociada con una cantidad de manifestaciones cutáneas y osteoarticulares. La más común de estas características afecta al pie (síndrome de pie diabético); sin embargo, similares lesiones se pueden observar en la mano (síndrome de mano diabética), generalmente asociadas a una larga evolución de la enfermedad, malos controles glicémicos y complicaciones microvasculares. En este artículo se realiza una revisión de la literatura para actualizar el diagnóstico y la terapéutica de manifestaciones musculo-esqueléticas en la mano de pacientes con DBT: movilidad articular limitada, contractura de Dupuytren, tenosinovitis del flexor (dedo en gatillo), infección por síndrome de mano diabética tropical, ulceración neuropática periférica, síndrome del túnel carpiano, neuropatía cubital y neuropatía en piel y uñas.(AU)
Diabetes mellitus (DBT) is a metabolic disorder caused by absolute or relative deficiency of insulin. This disorder has importance consequences in various organs and systems. It is well known that DBT is associated with cutaneous and osteoarticular manifestations; the most common of these complications affects the foot (diabetic foot syndrome). However, similar lesions can be observed in the hand (diabetic hand syndrome), usually associated with long standing disease, poor glycemic control and microvascular complications. This article makes a review of the literature to update diagnosis and therapy ofmusculoskeletal manifestations in patients with diabetic hand syndrome: limited joint mobility, DupuytrenÆs contracture, trigger finger, tropical diabetic hand, peripheral neuropathic ulceration, carpal tunnel syndrome, cubital neuropathy, and skin and nail changes.(AU)
Assuntos
Humanos , Insulina/deficiência , Contratura de Dupuytren/etiologia , Tenossinovite/etiologia , Complicações do Diabetes/complicações , Diabetes Mellitus/etiologia , Transtornos do Metabolismo de Glucose/diagnóstico , Limitação da Mobilidade , Neuropatias Diabéticas/etiologia , Síndrome do Túnel Carpal/etiologia , Neuropatias Ulnares/etiologiaRESUMO
This study tested whether chronic systemic administration of 5-aminoimidazole-4-carboxamide-1-ß-D-ribofuranoside (AICAR) could attenuate hyperphagia, reduce lean and fat mass losses, and improve whole-body energy homeostasis in insulin-deficient rats. Male Wistar rats were first rendered diabetic through streptozotocin (STZ) administration and then intraperitoneally injected with AICAR for 7 consecutive days. Food and water intake, ambulatory activity, and energy expenditure were assessed at the end of the AICAR-treatment period. Blood was collected for circulating leptin measurement and the hypothalami were extracted for the determination of suppressor of cytokine signaling 3 (SOCS3) content, as well as the content and phosphorylation of AMP-kinase (AMPK), acetyl-CoA carboxylase (ACC), and the signal transducer and activator of transcription 3 (STAT3). Rats were thoroughly dissected for adiposity and lean body mass (LBM) determinations. In non-diabetic rats, despite reducing adiposity, AICAR increased (â¼1.7-fold) circulating leptin and reduced hypothalamic SOCS3 content and food intake by 67% and 25%, respectively. The anorexic effect of AICAR was lost in diabetic rats, even though hypothalamic AMPK and ACC phosphorylation markedly decreased in these animals. Importantly, hypothalamic SOCS3 and STAT3 levels remained elevated and reduced, respectively, after treatment of insulin-deficient rats with AICAR. Diabetic rats were lethargic and displayed marked losses of fat and LBM. AICAR treatment increased ambulatory activity and whole-body energy expenditure while also attenuating diabetes-induced fat and LBM losses. In conclusion, AICAR did not reverse hyperphagia, but it promoted anti-catabolic effects on skeletal muscle and fat, enhanced spontaneous physical activity, and improved the ability of rats to cope with the diabetes-induced dysfunctional alterations in glucose metabolism and whole-body energy homeostasis.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Aminoimidazol Carboxamida/análogos & derivados , Hipotálamo/efeitos dos fármacos , Hipotálamo/metabolismo , Insulina/deficiência , Ribonucleosídeos/administração & dosagem , Ribonucleosídeos/farmacologia , Acetil-CoA Carboxilase/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Aminoimidazol Carboxamida/administração & dosagem , Aminoimidazol Carboxamida/farmacologia , Animais , Depressores do Apetite/administração & dosagem , Depressores do Apetite/farmacologia , Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus/sangue , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Diabetes Mellitus/fisiopatologia , Ingestão de Líquidos/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Hipotálamo/fisiopatologia , Insulina/sangue , Leptina/sangue , Leptina/metabolismo , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Fosforilação/efeitos dos fármacos , Ratos , Ratos Wistar , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína 3 Supressora da Sinalização de Citocinas , Proteínas Supressoras da Sinalização de Citocina/metabolismoRESUMO
AIMS: Diabetes mellitus is associated with metabolic bone disease and increased low-impact fractures. The insulin-sensitizer metformin possesses in vitro, in vivo and ex vivo osteogenic effects, although this has not been adequately studied in the context of diabetes. We evaluated the effect of insulin-deficient diabetes and/or metformin on bone microarchitecture, on osteogenic potential of bone marrow progenitor cells (BMPC) and possible mechanisms involved. METHODS: Partially insulin-deficient diabetes was induced in rats by nicotinamide/streptozotocin-injection, with or without oral metformin treatment. Femoral metaphysis micro-architecture, ex vivo osteogenic potential of BMPC, and BMPC expression of Runx-2, PPARγ and receptor for advanced glycation endproducts (RAGE) were investigated. RESULTS: Histomorphometric analysis of diabetic femoral metaphysis demonstrated a slight decrease in trabecular area and a significant reduction in osteocyte density, growth plate height and TRAP (tartrate-resistant acid phosphatase) activity in the primary spongiosa. BMPC obtained from diabetic animals showed a reduction in Runx-2/PPARγ ratio and in their osteogenic potential, and an increase in RAGE expression. Metformin treatment prevented the diabetes-induced alterations in bone micro-architecture and BMPC osteogenic potential. CONCLUSION: Partially insulin-deficient diabetes induces deleterious effects on long-bone micro-architecture that are associated with a decrease in BMPC osteogenic potential, which could be mediated by a decrease in their Runx-2/PPARγ ratio and up-regulation of RAGE. These diabetes-induced alterations can be totally or partially prevented by oral administration of metformin.
Assuntos
Células da Medula Óssea/citologia , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Insulina/deficiência , Metformina/uso terapêutico , Células-Tronco/citologia , Animais , Células da Medula Óssea/efeitos dos fármacos , Masculino , Osteogênese/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Células-Tronco/efeitos dos fármacosRESUMO
OBJECTIVES: Administering steroids before cardiopulmonary bypass in pediatric heart surgery modulates systemic inflammatory response syndrome and improves postoperative recovery. However, the use of steroids aggravates hyperglycemia, which is associated with a poor prognosis. Adult patients with systemic inflammatory response syndrome usually evolve with hyperglycemia and high insulin levels, whereas >90% of pediatric patients exhibit hyperglycemia and low insulin levels. This study aims to determine: A) the metabolic and inflammatory factors that are associated with hyperglycemia and low insulin levels in children who underwent cardiac surgery with cardiopulmonary bypass and who received a single high dose of methylprednisolone and B) the best predictors of insulin variation using a mathematical model. METHODS: This preliminary study recruited 20 children who underwent heart surgery with cardiopulmonary bypass and received methylprednisolone (30 mg/kg) immediately after anesthesia. Among the 20 patients initially recruited, one was excluded because of the absence of hyperglycemia and lower insulin levels after surgery. However, these abnormalities were confirmed in the remaining 19 children. The C-peptide, CRP, IL-6, and adrenomedullin levels were measured before surgery, immediately after cardiopulmonary bypass, and on the first, second, and third days after cardiac surgery. RESULTS: IL-6, CRP, and adrenomedullin increments were observed, whereas the C-peptide levels remained within reference intervals. CONCLUSION: The multiple regression model demonstrated that in addition to age and glycemia (two well-known factors that are directly involved in glucose metabolism), adrenomedullin and IL-6 levels were independent factors associated with lower insulin concentrations. These four parameters were responsible for 64.7% of the observed insulin variances. In addition, the fact that C-peptide levels did not fall together with insulin could have grounded the medical decision not to administer insulin to patients.
Assuntos
Anti-Inflamatórios/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/métodos , Ponte Cardiopulmonar/métodos , Hiperglicemia/induzido quimicamente , Insulina/sangue , Metilprednisolona/efeitos adversos , Adrenomedulina/sangue , Fatores Etários , Anti-Inflamatórios/administração & dosagem , Glicemia/análise , Glicemia/efeitos dos fármacos , Peptídeo C/sangue , Proteína C-Reativa/análise , Pré-Escolar , Feminino , Humanos , Lactente , Insulina/deficiência , Interleucina-6/sangue , Masculino , Metilprednisolona/administração & dosagem , Modelos Biológicos , Período Pós-Operatório , Valores de Referência , Análise de RegressãoRESUMO
OBJECTIVES: Administering steroids before cardiopulmonary bypass in pediatric heart surgery modulates systemic inflammatory response syndrome and improves postoperative recovery. However, the use of steroids aggravates hyperglycemia, which is associated with a poor prognosis. Adult patients with systemic inflammatory response syndrome usually evolve with hyperglycemia and high insulin levels, whereas >90% of pediatric patients exhibit hyperglycemia and low insulin levels. This study aims to determine: A) the metabolic and inflammatory factors that are associated with hyperglycemia and low insulin levels in children who underwent cardiac surgery with cardiopulmonary bypass and who received a single high dose of methylprednisolone and B) the best predictors of insulin variation using a mathematical model. METHODS: This preliminary study recruited 20 children who underwent heart surgery with cardiopulmonary bypass and received methylprednisolone (30 mg/kg) immediately after anesthesia. Among the 20 patients initially recruited, one was excluded because of the absence of hyperglycemia and lower insulin levels after surgery. However, these abnormalities were confirmed in the remaining 19 children. The C-peptide, CRP, IL-6, and adrenomedullin levels were measured before surgery, immediately after cardiopulmonary bypass, and on the first, second, and third days after cardiac surgery. RESULTS: IL-6, CRP, and adrenomedullin increments were observed, whereas the C-peptide levels remained within reference intervals. CONCLUSION: The multiple regression model demonstrated that in addition to age and glycemia (two well-known factors that are directly involved in glucose metabolism), adrenomedullin and IL-6 levels were independent factors associated with lower insulin concentrations. These four parameters were responsible for 64.7% of the observed insulin variances. In addition, the fact that C-peptide levels did not fall together with insulin could have grounded the medical decision not to administer insulin to patients.