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1.
Endocrinol. diabetes nutr. (Ed. impr.) ; 66(10): 647-653, dic. 2019. tab, graf
Artigo em Inglês | IBECS | ID: ibc-184792

RESUMO

Introduction: Several sweeteners are introduced to replace sucrose in the human diet. However, they had their own limitations and concerns, particularly in terms of their taste and their long-term health consequences. This study examined the effect of a new mixture of sugars and sugar alcohol on the postprandial blood glucose levels and its possible gastrointestinal (GI) adverse reactions in human adults. Methods: In this double-blind three-way randomized clinical trial, adults (21 with type 2 diabetes and 20 healthy) received 300 ml of three beverages containing 50 g glucose, sucrose, and lacritose (a mixture of lactose, fructose, sucrose, and erythritol) when they were in the fasted state in a random order. Postprandial serum glucose was checked every 30min up to 2 h and the gastrointestinal reactions were collected. Results: The mean serum glucose was significantly lower in all time points after ingestion of the lacritose for participants with type 2 diabetes compared to glucose and sucrose (P < 0.05). The blood glucose levels were significantly lower in the 30th and 60th min for healthy subjects (P < 0.05). Adverse GI reactions were not significant between the test beverages. Conclusions: The ingestion of a 50 g dose of lacritose containing lactose, fructose, sucrose, and erythritol, led to an improved blood glucose levels without any significant adverse effect compared to the same amount of glucose and sucrose. Studying the long-term effects of lacritose on appetite, metabolic markers and adverse reactions is recommended. The trial was registered in Iranian registry of clinical trials: IRCT2015050912571N2


Introducción: Se han utilizado varios edulcorantes para sustituir a la sacarosa en la dieta humana. Sin embargo, tenían sus propias limitaciones y problemas, sobre todo por su sabor y sus consecuencias a largo plazo para la salud. En este estudio se explora el efecto de una nueva muestra de azúcares y alcohol de azúcar en los niveles de glucemia posprandial y las posibles reacciones adversas digestivas a ella en adultos humanos. Métodos: En este ensayo clínico doble ciego aleatorizado de tres vías, adultos (21 con diabetes tipo 2 y 20 sanos) recibieron 300ml de tres bebidas que contenían 50 g de glucosa, sacarosa y lacritosa (una mezcla de lactosa, fructosa, sacarosa y eritritol) en orden aleatorio en ayunas. Se comprobó la glucose sérica posprandial cada 30 minutos hasta las dos horas y se recogieron las reacciones digestivas. Resultados: Los valores medios de glucosa en suero eran significativamente menores en todos los puntos temporales tras la ingesta de lacritosa que tras la de glucosa y sacarosa en los participantes con diabetes tipo 2 (P < 0,05). Los niveles de glucemia eran significativamente menores a los 30 y 60 minutos en los sujetos sanos (P < 0,05). No había diferencias significativas en las reacciones digestivas adversas entre las bebidas estudiadas. Conclusiones: La ingesta de una dosis de 50 g de lacritosa que contiene lactosa, fructosa, sacarosa y eritritol, mejoró los niveles de glucemia sin efectos adversos importantes comparada con la misma cantidad de glucosa y sacarosa. Se recomienda estudiar los efectos a largo plazo de la lacritosa en el apetito, los marcadores metabólicos y las reacciones adversas. El ensayo se inscribió en el registro de ensayos clínicos de Irán: IRCT2015050912571N2


Assuntos
Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Glicemia/análise , Sacarose/sangue , Hiperglicemia/sangue , Hiperglicemia/induzido quimicamente , Álcoois Açúcares/análise , Sacarose/efeitos adversos , Índice Glicêmico , Hiperglicemia/complicações , Método Duplo-Cego , Álcoois Açúcares/efeitos adversos , Álcoois Açúcares/sangue , Antropometria
2.
Nat Med ; 25(11): 1733-1738, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31700171

RESUMO

The G-protein-coupled receptor accessory protein MRAP2 is implicated in energy control in rodents, notably via the melanocortin-4 receptor1. Although some MRAP2 mutations have been described in people with obesity1-3, their functional consequences on adiposity remain elusive. Using large-scale sequencing of MRAP2 in 9,418 people, we identified 23 rare heterozygous variants associated with increased obesity risk in both adults and children. Functional assessment of each variant shows that loss-of-function MRAP2 variants are pathogenic for monogenic hyperphagic obesity, hyperglycemia and hypertension. This contrasts with other monogenic forms of obesity characterized by excessive hunger, including melanocortin-4 receptor deficiency, that present with low blood pressure and normal glucose tolerance4. The pleiotropic metabolic effect of loss-of-function mutations in MRAP2 might be due to the failure of different MRAP2-regulated G-protein-coupled receptors in various tissues including pancreatic islets.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Predisposição Genética para Doença , Hiperfagia/genética , Obesidade/genética , Adolescente , Adulto , Criança , Metabolismo Energético/genética , Feminino , Humanos , Hiperglicemia/complicações , Hiperglicemia/genética , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Hiperfagia/complicações , Hiperfagia/metabolismo , Hiperfagia/patologia , Hipertensão/complicações , Hipertensão/genética , Hipertensão/metabolismo , Hipertensão/patologia , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Mutação com Perda de Função/genética , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Obesidade/patologia , Receptor Tipo 4 de Melanocortina/genética , Fatores de Risco , Adulto Jovem
3.
Acta Neurol Scand ; 140(6): 443-448, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31518433

RESUMO

OBJECTIVES: Hyperglycemia is a predictor for poor stroke outcome. Hyperglycemic stroke patients treated with thrombolysis have an increased risk of intracranial hemorrhage. Insulin is the gold standard for treating hyperglycemia but comes with a risk of hypoglycemia. Glucagon-like peptide-1 receptor agonists (GLP-1RA) are drugs used in type 2 diabetes that have a low risk of hypoglycemia and have been shown to exert neuroprotective effects. The primary objective was to determine whether prehospital administration of the GLP-1RA exenatide could lower plasma glucose in stroke patients. Secondary objective was to study tolerability and safety. MATERIALS & METHODS: Randomized controlled trial comparing exenatide administrated prehospitally with a control group receiving standard care for hyperglycemia. Patients with Face Arm Speech Test ≥1 and glucose ≥8 mmol/L were randomized. Glucose was monitored for 24 hours. All adverse events were recorded. RESULTS: Nineteen patients were randomized, eight received exenatide. An interim recruitment failure analysis with subsequent changes of the protocol was made. The study was stopped prematurely due to slow inclusion. No difference was observed in the main outcome of plasma glucose at 4 hours, control vs exenatide (mean, SD); 7.0 ± 1.9 vs 7.6 ± 1.6; P = .56). No major adverse events were reported. CONCLUSIONS: We found no evidence that prehospital exenatide had effect on hyperglycemia. However, it was given without adverse events in this study with limited sample size that was prematurely stopped due to slow inclusion.


Assuntos
Glicemia/efeitos dos fármacos , Exenatida/administração & dosagem , Hiperglicemia/prevenção & controle , Hipoglicemiantes/administração & dosagem , Acidente Vascular Cerebral/sangue , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hiperglicemia/complicações , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações
4.
Zhonghua Wai Ke Za Zhi ; 57(10): 31-37, 2019 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-31510730

RESUMO

Objective: To examine the association of hyperglycemia and postoperative complications in non-diabetic patients underwent pancreaticoduodenectomy(PD). Methods: The clinical data of 209 non-diabetic patients who underwent PD from January 2012 to June 2018 at Department of Pancreatic and Biliary Surgery, the First Affiliated Hospital of Harbin Medical University and met the inclusion criteria were retrospectively analyzed. According to the diagnostic criteria of postoperative hyperglycemia, the patients were divided into postoperative hyperglycemia group (167 cases, 79.9%) and control group(42 cases, 20.1%). The propensity score matching(PSM) method was used to eliminate the difference between groups(caliper value=0.02; 38 cases in control group including 30 males and 8 females with age of 59.0 years;38 cases in postoperative hyperglycemia group including 32 males and 6 females with age of 61.0 years;37 cases of pancreatic head carcinoma,30 cases of periampullary carcinoma and 9 cases of benign diseases). A comparative analysis was applied for preoperative data, surgical related indicators and postoperative complication rates.The receiver operating characteristic(ROC) curve was used to calculate the area under the curve(AUC) of blood glucose values on postoperative day 1,3 and 5(POD1, POD3, POD5), to determine the high-risk blood glucose cutoff value of complications and to evaluate its sensitivity and specificity for the prediction of postoperative complications. Results: Univariate analysis showed that the differences in gender, body mass index, preoperative blood glucose, and serum urea nitrogen levels were statistically significant before PSM.There was no significant difference in the preoperative data between the two groups after PSM. Compared with the control group, the incidence of postoperative pancreatic fistula (31.6% vs. 5.3%), abdominal infection(29.0% vs. 7.9%) and Clavien-Dindo Ⅲ-Ⅴ complications(31.6% vs.7.9%) were statistically different(χ(2)=7.092,P=0.008; χ(2)=4.290,P=0.038; χ(2)=5.316,P=0.021), respectively. According to the AUC on POD3,the blood glucose value ≥8.860 mmol/L was an independent risk factor for pancreatic fistula with sensitivity of 58.3% and specificity of 76.9%,the blood glucose value ≥9.130 mmol/L was an independent risk factor for abdominal infection with sensitivity of 54.5% and specificity of 81.5% and the blood glucose value ≥7.685 mmol/L was independent risk factor of Clavien-Dindo Ⅲ-Ⅴ complications with sensitivity of 75.0% and specificity of 57.7%. Conclusions: Postoperative hyperglycemia in non-diabetic patients is associated with postoperative pancreatic fistula, abdominal infection, and Clavien-Dindo Ⅲ-Ⅴ complications.According to the early postoperative blood glucose value,the occurrence of postoperative pancreatic fistula, abdominal infection and Clavien-Dindo Ⅲ- Ⅴ complications can be effectively predicted.


Assuntos
Hiperglicemia/complicações , Pancreaticoduodenectomia/efeitos adversos , Feminino , Humanos , Hiperglicemia/sangue , Infecções Intra-Abdominais/etiologia , Masculino , Pessoa de Meia-Idade , Pancreatopatias/cirurgia , Fístula Pancreática/etiologia , Complicações Pós-Operatórias/classificação , Valor Preditivo dos Testes , Estudos Retrospectivos
5.
J Diabetes Res ; 2019: 8153140, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31467929

RESUMO

A variety of animal models of diabetes mellitus (DM) are required to study the genetics and pathophysiology of DM. We established a novel rat strain showing nonobese type 2 diabetes with enlarged kidneys from the LEA.PET-pet congenic strain and named it Diabetes with Enlarged Kidney (DEK). The body growth of DEK affected rats was similar to that of normal rats before the development of DM but was attenuated with the deterioration of DM. There was a marked difference in the etiology of DEK by gender: DM phenotypes including polyuria, polydipsia, and hyperglycemia (nonfasting blood glucose over 300 mg/dl) were found in male rats aged over 10 weeks but not in female rats. The cumulative incidence of DM in DEK males at the age of 30 weeks was 44.8%. Oral glucose tolerance tests showed glucose intolerance and decreased insulin secretion in response to glucose loading in affected males, features which were exacerbated with age. Affected males exhibited disorganized architecture of pancreatic islets, decreased numbers of ß cells, and markedly decreased expression of insulin, despite no pathological findings of hemorrhage or infiltration of inflammatory cells in the pancreatic islet. Age-related islet fibrosis appeared similar in normal and affected males. Affected males also showed enlarged kidneys with dilation of renal tubules in both the cortex and medulla, but no obvious glomerular lesions typical of diabetic nephropathy (DN) at the age of 30 weeks. Plasma levels of urea nitrogen and creatinine were normal, but hypoalbuminemia was detected. These pathophysiological features in affected males indicated that their renal function was almost maintained despite severe DM. Taken together, these findings indicate that the affected males of the DEK strain are a novel nonobese type 2 diabetes rat model useful for studying the mechanisms underlying ß cell loss and identifying genetic factors protective against DN.


Assuntos
Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/patologia , Nefropatias Diabéticas/etiologia , Rim/patologia , Animais , Animais Congênicos , Glicemia/análise , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/patologia , Feminino , Teste de Tolerância a Glucose , Hiperglicemia/complicações , Hiperglicemia/patologia , Hipertrofia/sangue , Hipertrofia/etiologia , Masculino , Polidipsia/etiologia , Polidipsia/patologia , Poliúria/etiologia , Poliúria/patologia , Ratos , Ratos Endogâmicos
6.
Postgrad Med ; 131(7): 423-437, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31382796

RESUMO

Hyperglycemia on hospital admission is a common phenomenon in acute ischemic stroke patients and represents an independent predictor of poor clinical outcome with or without acute recanalization therapies (systemic thrombolysis or mechanical thrombectomy). Effective restoration of normoglycemia is considered to be beneficial, but conclusive evidence from randomized controlled clinical trials and specific recommendations are lacking. In addition, aggressive glucose control can be complicated by hypoglycemia leading to early neurological deterioration. We conducted a systematic literature review with the aim of addressing several questions: timing of glucose control, target range, type of insulin delivery, duration and practicability of glucose-lowering protocols. Special issues regarding mechanical thrombectomy and glycemic variability can then be investigated in future trials which are also being considered.


Assuntos
Isquemia Encefálica/terapia , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Acidente Vascular Cerebral/terapia , Glicemia/metabolismo , Isquemia Encefálica/complicações , Isquemia Encefálica/metabolismo , Hospitalização , Humanos , Hiperglicemia/complicações , Hiperglicemia/metabolismo , Hipoglicemia/induzido quimicamente , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/metabolismo , Trombectomia , Terapia Trombolítica
7.
Int J Mol Sci ; 20(15)2019 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-31382355

RESUMO

NADPH oxidases (NOX) are enzyme complexes that have received much attention as key molecules in the development of vascular dysfunction. NOX have the primary function of generating reactive oxygen species (ROS), and are considered the main source of ROS production in endothelial cells. The endothelium is a thin monolayer that lines the inner surface of blood vessels, acting as a secretory organ to maintain homeostasis of blood flow. The enzymatic production of nitric oxide (NO) by endothelial NO synthase (eNOS) is critical in mediating endothelial function, and oxidative stress can cause dysregulation of eNOS and endothelial dysfunction. Insulin is a stimulus for increases in blood flow and endothelium-dependent vasodilation. However, cardiovascular disease and type 2 diabetes are characterized by poor control of the endothelial cell redox environment, with a shift toward overproduction of ROS by NOX. Studies in models of type 2 diabetes demonstrate that aberrant NOX activation contributes to uncoupling of eNOS and endothelial dysfunction. It is well-established that endothelial dysfunction precedes the onset of cardiovascular disease, therefore NOX are important molecular links between type 2 diabetes and vascular complications. The aim of the current review is to describe the normal, healthy physiological mechanisms involved in endothelial function, and highlight the central role of NOX in mediating endothelial dysfunction when glucose homeostasis is impaired.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Endotélio Vascular/fisiopatologia , Hiperglicemia/fisiopatologia , NADPH Oxidases/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Animais , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Doenças Cardiovasculares/fisiopatologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Endotélio Vascular/metabolismo , Glucose/metabolismo , Humanos , Hiperglicemia/complicações , Hiperglicemia/metabolismo , Espécies Reativas de Oxigênio/metabolismo
9.
Surgery ; 166(4): 655-662, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31351669

RESUMO

BACKGROUND: The relationship between preoperative hyperglycemia and complications after surgery is not well defined. We compared the relationship of preoperative versus postoperative hyperglycemia on clinical outcomes and assessed if preoperative hyperglycemia was a predictor for postoperative hyperglycemia in patients undergoing elective colorectal surgery. METHODS: We performed a retrospective review of an institutional database for patients who underwent elective colorectal resection between July 2015 and June 2017. Data regarding patient characteristics, history of diabetes, preoperative and postoperative hyperglycemic events, and postoperative complications were collected. Bivariate and multivariate logistic analyses were used to assess relationships. RESULTS: Of 755 surgical operations reviewed, preoperative hyperglycemia >180 mg/dL was not significantly associated with adverse outcomes in an adjusted model. Only postoperative hyperglycemia >180 mg/dL was significantly associated with complications, including acute kidney injury (odds ratio 2.58, P < 0.001), anastomotic leak (odds ratio 2.64, P = 0.01), arrhythmia (odds ratio 2.40, P = 0.009), and sepsis (odds ratio 3.86, P < 0.001). Preoperative hyperglycemia remained a significant predictor of postoperative hyperglycemia (odds ratio 4.91, P < 0.001). CONCLUSION: Postoperative hyperglycemia was more significantly associated with adverse clinical outcomes after elective colorectal surgery than was preoperative hyperglycemia. However, preoperative hyperglycemia was associated with postoperative hyperglycemia, suggesting that improved glycemic management preoperatively may help reduce hyperglycemic events after surgery.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Procedimentos Cirúrgicos Eletivos/métodos , Hiperglicemia/complicações , Hiperglicemia/diagnóstico , Idoso , Estudos de Coortes , Neoplasias Colorretais/patologia , Bases de Dados Factuais , Intervalo Livre de Doença , Procedimentos Cirúrgicos Eletivos/mortalidade , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/fisiopatologia , Período Pós-Operatório , Valor Preditivo dos Testes , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida
10.
J Exp Clin Cancer Res ; 38(1): 327, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337431

RESUMO

Malignant tumors are often multifactorial. Epidemiological studies have shown that hyperglycemia raises the prevalence and mortality of certain malignancies, like breast, liver, bladder, pancreatic, colorectal, endometrial cancers. Hyperglycemia can promote the proliferation, invasion and migration, induce the apoptotic resistance and enhance the chemoresistance of tumor cells. This review focuses on the new findings in the relationship between hyperglycemia and tumor development.


Assuntos
Progressão da Doença , Hiperglicemia/metabolismo , Neoplasias/metabolismo , Apoptose/genética , Proliferação de Células/genética , Resistencia a Medicamentos Antineoplásicos/genética , Glucose/metabolismo , Humanos , Hiperglicemia/complicações , Hiperglicemia/patologia , Neoplasias/complicações , Neoplasias/genética , Neoplasias/patologia
11.
J Korean Med Sci ; 34(29): e202, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31347313

RESUMO

BACKGROUND: Diabetes mellitus (DM) causes macro- and microvasculopathy, but data on cardiac microvascular changes in large animals are scarce. We sought to determine the effect of DM on macro- and microvascular changes in diabetic pigs and humans. METHODS: Eight domestic pigs (4 with type I diabetes and 4 controls) underwent coronary angiography with optical coherence tomography (OCT; at baseline and 1 and 2 months), coronary computed tomography angiography, cardiac magnet resonance (CMR) imaging, and histologic examination. RESULTS: The diabetic pigs had more irregular capillaries with acellular capillaries and a smaller capillary diameter (11.7 ± 0.33 µm vs. 13.5 ± 0.53 µm; P < 0.001) than those of the control pigs. The OCT showed no significant epicardial stenosis in either group; however diabetic pigs had a greater intima-media thickness. CMR results showed that diabetic pigs had a lower relative upslope at rest (31.3 ± 5.9 vs. 37.9 ± 8.1; P = 0.011) and during stress (18.0 ± 3.0 vs. 21.6 ± 2.8; P = 0.007) than the control pigs, implying decreased myocardial perfusion. Among the 79 patients with ST elevation myocardial infarction, 25 had diabetes and they had lower myocardial perfusion on CMR as well. CONCLUSION: DM causes microvascular remodeling and a decrease in myocardial perfusion in large animals at a very early stage of the disease course. Early and effective interventions are necessary to interrupt the progression of vascular complications in diabetic patients.


Assuntos
Circulação Coronária/fisiologia , Diabetes Mellitus Tipo 1/patologia , Hiperglicemia/patologia , Infarto do Miocárdio/patologia , Idoso , Animais , Capilares/diagnóstico por imagem , Capilares/fisiologia , Espessura Intima-Media Carotídea , Angiografia Coronária , Diabetes Mellitus Tipo 1/complicações , Modelos Animais de Doenças , Feminino , Hemoglobina A Glicada/análise , Coração/diagnóstico por imagem , Coração/fisiopatologia , Humanos , Hiperglicemia/complicações , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico por imagem , Estudos Retrospectivos , Suínos , Tomografia de Coerência Óptica
12.
JAMA ; 322(4): 326-335, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31334795

RESUMO

Importance: Hyperglycemia during acute ischemic stroke is common and is associated with worse outcomes. The efficacy of intensive treatment of hyperglycemia in this setting remains unknown. Objectives: To determine the efficacy of intensive treatment of hyperglycemia during acute ischemic stroke. Design, Setting, and Participants: The Stroke Hyperglycemia Insulin Network Effort (SHINE) randomized clinical trial included adult patients with hyperglycemia (glucose concentration of >110 mg/dL if had diabetes or ≥150 mg/dL if did not have diabetes) and acute ischemic stroke who were enrolled within 12 hours from stroke onset at 63 US sites between April 2012 and August 2018; follow-up ended in November 2018. The trial included 1151 patients who met eligibility criteria. Interventions: Patients were randomized to receive continuous intravenous insulin using a computerized decision support tool (target blood glucose concentration of 80-130 mg/dL [4.4-7.2 mmol/L]; intensive treatment group: n = 581) or insulin on a sliding scale that was administered subcutaneously (target blood glucose concentration of 80-179 mg/dL [4.4-9.9 mmol/L]; standard treatment group: n = 570) for up to 72 hours. Main Outcomes and Measures: The primary efficacy outcome was the proportion of patients with a favorable outcome based on the 90-day modified Rankin Scale score (a global stroke disability scale ranging from 0 [no symptoms or completely recovered] to 6 [death]) that was adjusted for baseline stroke severity. Results: Among 1151 patients who were randomized (mean age, 66 years [SD, 13.1 years]; 529 [46%] women, 920 [80%] with diabetes), 1118 (97%) completed the trial. Enrollment was stopped for futility based on prespecified interim analysis criteria. During treatment, the mean blood glucose level was 118 mg/dL (6.6 mmol/L) in the intensive treatment group and 179 mg/dL (9.9 mmol/L) in the standard treatment group. A favorable outcome occurred in 119 of 581 patients (20.5%) in the intensive treatment group and in 123 of 570 patients (21.6%) in the standard treatment group (adjusted relative risk, 0.97 [95% CI, 0.87 to 1.08], P = .55; unadjusted risk difference, -0.83% [95% CI, -5.72% to 4.06%]). Treatment was stopped early for hypoglycemia or other adverse events in 65 of 581 patients (11.2%) in the intensive treatment group and in 18 of 570 patients (3.2%) in the standard treatment group. Severe hypoglycemia occurred only among patients in the intensive treatment group (15/581 [2.6%]; risk difference, 2.58% [95% CI, 1.29% to 3.87%]). Conclusions and Relevance: Among patients with acute ischemic stroke and hyperglycemia, treatment with intensive vs standard glucose control for up to 72 hours did not result in a significant difference in favorable functional outcome at 90 days. These findings do not support using intensive glucose control in this setting. Trial Registration: ClinicalTrials.gov Identifier: NCT01369069.


Assuntos
Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Acidente Vascular Cerebral/complicações , Idoso , Isquemia Encefálica/complicações , Feminino , Fibrinolíticos/uso terapêutico , Humanos , Hiperglicemia/complicações , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Infusões Intravenosas , Injeções Subcutâneas , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento
13.
Medicine (Baltimore) ; 98(28): e16255, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305406

RESUMO

RATIONALE: Hemichorea-hemiballism, a rare manifestation of non-ketotic hyperglycemia, characterized by involuntary arrhythmic motions involving one side of the body, results from focal lesions in the contralateral caudate nucleus and putamen. Hyperkinetic disorders can be complications of uncontrolled diabetes mellitus and should not be ignored. PATIENT CONCERNS: We present the case of a 39-year-old woman who presented to the emergency department with a 3-day history of left-sided hemichorea-hemiballism. She had type 2 diabetes mellitus with poor control and maintenance of regular hemodialysis. DIAGNOSES: The patient was diagnosed as hyperglycemia, normal ketone body and hemichorea-hemiballism based on laboratory examination, computed tomography (CT) scan, and brain magnetic resonance image (MRI). INTERVENTIONS: Intensive glycemic control via insulin injection was prescribed for correction of hyperglycemia. OUTCOMES: The unilateral involuntary movements subsided progressively over four weeks. The patient's hemichorea had completely resolved at the three-month follow-up. LESSONS: This unusual clinical presentation is often accompanied by severe hyperglycemia. Appropriate blood glycemic control is important. If physicians recognize and provide early treatment for this disease, it is usually treatable and has a good prognosis.


Assuntos
Coreia/complicações , Diabetes Mellitus Tipo 2/complicações , Discinesias/complicações , Hiperglicemia/complicações , Adulto , Coreia/diagnóstico , Coreia/tratamento farmacológico , Coreia/fisiopatologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/fisiopatologia , Diagnóstico Diferencial , Discinesias/diagnóstico , Discinesias/tratamento farmacológico , Discinesias/fisiopatologia , Feminino , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/tratamento farmacológico , Hiperglicemia/fisiopatologia
14.
Int J Mol Sci ; 20(13)2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31269778

RESUMO

The high incidence and poor prognosis of heart failure (HF) patients affected with diabetes (DM) is in part related to a specific cardiac remodeling currently recognized as diabetic cardiomyopathy (DCM). This cardiac frame occurs regardless of the presence of coronary artery diseases (CAD) and it can account for 15-20% of the total diabetic population. The pathogenesis of DCM remains controversial, and several molecular and cellular alterations including myocardial hypertrophy, interstitial fibrosis, oxidative stress and vascular inflammation, have been postulated. The main cardio-vascular alterations associated with hyperglycemia comprise endothelial dysfunction, adverse effects of circulating free fatty acids (FFA) and increased systemic inflammation. High glucose concentrations lead to a loss of mitochondrial networks, increased reactive oxygen species (ROS), endothelial nitric oxide synthase (eNOS) activation and a reduction in cGMP production related to protein kinase G (PKG) activity. Current mechanisms enhance the collagen deposition with subsequent increased myocardial stiffness. Several concerns regarding the exact role of DCM in HF development such as having an appearance as either dilated or as a concentric phenotype and whether diabetes could be considered a causal factor or a comorbidity in HF, remain to be clarified. In this review, we sought to explain the different DCM subtypes and the underlying pathophysiological mechanisms. Therefore, the traditional and new molecular and signal alterations and their relationship with macroscopic structural abnormalities are described.


Assuntos
Cardiomiopatias Diabéticas/patologia , Miocárdio/patologia , Animais , Cardiomiopatias Diabéticas/etiologia , Cardiomiopatias Diabéticas/genética , Cardiomiopatias Diabéticas/metabolismo , Regulação da Expressão Gênica , Produtos Finais de Glicação Avançada/genética , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Hiperglicemia/complicações , Hiperglicemia/genética , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Inflamação/complicações , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo
15.
Blood Coagul Fibrinolysis ; 30(6): 270-276, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31259777

RESUMO

: It is established that hyperglycemia directly effects the platelet functions and fibrin structure. In this study, we aimed to investigate the predictive value of hyperglycemia on thrombus burden in nondiabetic patients with ST-segment elevation myocardial infarction (STEMI) who underwent to primer percutaneous coronary intervention (PPCI). We enrolled 619 nondiabetic patients with STEMI who received PPCI. Patients were divided two groups according to thrombus burden. Stress hyperglycemia was determined as blood glucose concentration more than 180 mg/dl and angiographic coronary thrombus burden was scored based on thrombolysis in myocardial infarction thrombus grades. Patients with thrombus grades 4 were defined as large thrombus burden (LTB), patients with thrombus burden less than thrombus grades 4 were defined as small thrombus burden. A total of 68 (11.0%) STEMI patients had stress hyperglycemia, while 223 (36.0%) patients had LTB. Sex, the prevalence of hypertension, smoking, and dyslipidemia were not different between the thrombus burden groups (P > 0.05 for all parameters). Compared with the patients with small thrombus burden, the patients with LTB were had significantly higher admission blood glucose concentrations (135 ±â€Š39.1 mg/dl vs. 145.9 ±â€Š43.1, P = 0.002, respectively). The multivariate logistic regression analysis demonstrated that stress hyperglycemia is an independent predictor of LTB (odds ratio: 3.025, confidence interval 1.200-7.622, P = 0.019). Admission hyperglycemia is associated with the LTB which cause adverse cardiac outcomes. Hyperglycemia may play a role on thrombus development.


Assuntos
Hiperglicemia/complicações , Valor Preditivo dos Testes , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Trombose/etiologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea , Fatores de Risco , Índice de Gravidade de Doença
16.
Rev. chil. endocrinol. diabetes ; 12(3): 170-174, jul. 2019. tab
Artigo em Espanhol | LILACS | ID: biblio-1006512

RESUMO

Objetivo: El objetivo del estudio fue describir las características y evolución de los pacientes que acudieron a las urgencias de nuestro hospital y fueron diagnosticados de cetoacidosis diabética (CAD) utilizando la novedosa herramienta de Big Data Savana. Método: Estudio retrospectivo descriptivo de los pacientes atendidos en urgencias del Hospital Universitario Infanta Leonor durante los años 2011 al 2016 con diagnóstico de CAD. La búsqueda se realizó con Savana Manager. Resultados: Se diagnosticaron 95 episodios de CAD en 68 pacientes. Del total de episodios de CAD, 57 fueron en diabéticos tipo 1 (de ellos 4 LADA), 25 en diabéticos tipo 2, 2 en diabéticos postpancreatectomía y 12 fueron debuts diabéticos. Del total, 61 (64,2%) requirieron ingreso hospitalario, de ellos 23 (24,2%) ingresaron en UCI. La media de HbA1c fue de 10,6 ± 2,1%. Tres pacientes requirieron reingreso tras el alta. La mortalidad fue muy baja con el fallecimiento en 1 paciente diagnosticado simultáneamente de cáncer pulmonar. Los desencadenantes de la CAD fueron: 35 casos (36,8%) falta de adherencia al tratamiento, 31 (32,6%) infecciones, 12 (12,6%) debuts, 8 (8,4%) varias causas y 9 (9,5%) no se pudo determinar la causa. Se clasificaron como CAD de gravedad leve un 28%, un 38% como de gravedad moderada y 34% como graves. La duración del ingreso no se relacionó con la severidad de la cetoacidosis. Conclusiones: La CAD es una complicación grave que afecta tanto a diabéticos tipo 1 como a tipo 2 con elevado porcentaje de ingresos hospitalarios y en UCI, aunque con baja mortalidad en nuestro medio. La duración de los ingresos no se relaciona con la severidad del cuadro.


Objective: the study was designed to describe the clinical features and evolution of the diabetic patients attended in our hospital emergency department with diabetic ketoacidosis (DKA) using the novel Big Data tool Savana. Method: Retrospective descriptive study of the patients attended in the emergency room of the Infanta Leonor University Hospital during the years 2011 to 2016 with diagnosis of CAD. The search was made with Savana. Results: 95 episodes of DKA were diagnosed in 68 patients. Of the total episodes of CAD 57 were in type 1 diabetics (of which 4 were LADA), 25 in type 2 diabetics, 2 in diabetics postpancreatectomy and 12 were new onset of diabetes. Of the total, 61 (64.2%) required hospital admission, of which 23 (24.2%) were admitted to the intensive care unit (ICU). The mean HbA1c was 10.6 ± 2.1%. Three patients required readmission after discharge. Mortality was very low with death in 1 patient simultaneously diagnosed of lung cancer. The triggers of CAD were: 35 cases (36,8%) lack of adherence to treatment, 31 (32.6%) infections, 12 (12.6%) new onset, 8 (8,4%) various causes and 9 (9.5%) the cause could not be determined. They were classified as mild DKA 28%, 38% as moderate and 34% as severe. The duration of admission was not related to the severity of ketoacidosis. Conclusions: DKA is a serious complication that affects both, type 1 and type 2 diabetics patients, with a high percentage of hospital and ICU admissions, although with low mortality in our environment. The lenght of the stay in hospital is not related to the severity of the DKA.


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Cetoacidose Diabética/epidemiologia , Complicações do Diabetes/epidemiologia , Espanha/epidemiologia , Informática Médica , Epidemiologia Descritiva , Estudos Retrospectivos , Cetoacidose Diabética/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Serviço Hospitalar de Emergência , Hiperglicemia/complicações , Hiperglicemia/epidemiologia
17.
Biochim Biophys Acta Mol Cell Res ; 1866(9): 1398-1411, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31150695

RESUMO

Emerging evidence suggests that arginase contributes to endothelial dysfunction in diabetes. Intracellular signaling pathways, which interplay between arginase and eNOS enzyme activity leading to the development of endothelial dysfunction in hyperglycemia are not fully understood. Here, we analyzed the possible involvement of hyperglycemia (HG) induced arginase expression in eNOS protein regulation and activity and also the impact of arginase inhibition on eNOS activity. Furthermore, the roles of p38 MAPK and Erk1/2 phosphorylation in upregulation of arginase expression and eNOS dysregulation in endothelial cells (ECs) under hyperglycemia were evaluated. Protein analysis showed a concurrent increase in arginase I expression and decrease in eNOS expression and phosphorylation at Ser1177 under HG conditions. There was no simultaneous change in phosphorylation of eNOS at Thr495 in HG. Arginase inhibition prevented increased arginase activity, restored impaired NO bioavailability and reduced superoxide anion generation. Inhibition of MAP-kinases demonstrated that, unlike Erk1/2, p38 MAPK is an upstream activator in a signaling cascade leading to increased arginase I in HG conditions. P38 MAPK protein expression and phosphorylation were increased in response to HG. In the presence of a p38 MAPK inhibitor, HG-induced arginase expression was blunted. Although Erk1/2 was activated in HG, increased arginase expression was not blocked by co-treatment with an Erk1/2 inhibitor. Activation of both, p38 MAPK and Erk1/2 in HG, induced a downregulation in eNOS activity. Hence, applying MAPK inhibitors increased eNOS phosphorylation in HG. In conclusion, these findings demonstrate contributions of arginase I in the development of endothelial cell dysfunction under HG conditions via impaired eNOS regulation, which maybe mediated by p38 MAPK.


Assuntos
Arginase/metabolismo , Células Endoteliais/metabolismo , Hiperglicemia/metabolismo , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Óxido Nítrico Sintase Tipo III/metabolismo , Humanos , Hiperglicemia/complicações , Sistema de Sinalização das MAP Quinases , Fosforilação , Inibidores de Proteínas Quinases/farmacologia , Transdução de Sinais/efeitos dos fármacos , Superóxidos , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
18.
Int Immunopharmacol ; 74: 105672, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31195189

RESUMO

Metformin is the first line drug in the treatment of type 2 diabetes, however, little is known about its therapeutic potential to prevent or delay damage to the peripheral nerve. Thus, the aim of this study was to investigate whether metformin is able to attenuate the neuroinflammatory response in sciatic nerve of insulin-dependent diabetic mice. Swiss Webster mice were divided into four groups: Control, Diabetic (STZ), Diabetic +100 mg/kg/day of metformin (STZ + M100) and Diabetic +200 mg/kg/day of metformin. Diabetes was induced by streptozotocin (90 mg/kg, i.p.). Only animals with glycemia ≥270 mg/dl were considered diabetics. Metformin prevented atrophy of myelinated axons, and reduced expression of inflammatory mediators (interleukin-1ß, inducible nitric oxide synthase and nitric oxide). However, treatment with 200 mg of metformin was more effective in increasing neurotrophic (myelin basic protein and neural growth factor), angiogenic (vascular endothelial growth factor) and anti-inflammatory (inhibitor kappa B-alpha and interleukin 10) factors. Thus, metformin treatment, especially at the dose of 200 mg, protected the nerve from damages related to chronic hyperglycemia.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Neuropatias Diabéticas/prevenção & controle , Hipoglicemiantes/uso terapêutico , Metformina/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Animais , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Camundongos , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/metabolismo
19.
Lakartidningen ; 1162019 Mar 26.
Artigo em Sueco | MEDLINE | ID: mdl-31192395

RESUMO

We present a case of hemichorea/hemiballism, a rare complication of hyperglycemia. Diagnosis is made clinically by signs of unilateral involuntary movements of the extremities combined with typical neuroradiological findings in the basal ganglia. Guidelines for treatment of the condition are lacking but in many cases correction for hyperglycemia is sufficient for full symptom relief. In other cases, symptomatic treatment with haloperidol and tetrabenazine can be used.


Assuntos
Coreia/etiologia , Discinesias/etiologia , Hiperglicemia/complicações , Idoso de 80 Anos ou mais , Antidiscinéticos/uso terapêutico , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/patologia , Coreia/tratamento farmacológico , Discinesias/tratamento farmacológico , Feminino , Haloperidol/uso terapêutico , Humanos , Hiperglicemia/diagnóstico por imagem , Hiperglicemia/terapia , Imagem por Ressonância Magnética , Tomografia Computadorizada por Raios X
20.
Nat Rev Dis Primers ; 5(1): 41, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31197153

RESUMO

The global epidemic of prediabetes and diabetes has led to a corresponding epidemic of complications of these disorders. The most prevalent complication is neuropathy, of which distal symmetric polyneuropathy (for the purpose of this Primer, referred to as diabetic neuropathy) is very common. Diabetic neuropathy is a loss of sensory function beginning distally in the lower extremities that is also characterized by pain and substantial morbidity. Over time, at least 50% of individuals with diabetes develop diabetic neuropathy. Glucose control effectively halts the progression of diabetic neuropathy in patients with type 1 diabetes mellitus, but the effects are more modest in those with type 2 diabetes mellitus. These findings have led to new efforts to understand the aetiology of diabetic neuropathy, along with new 2017 recommendations on approaches to prevent and treat this disorder that are specific for each type of diabetes. In parallel, new guidelines for the treatment of painful diabetic neuropathy using distinct classes of drugs, with an emphasis on avoiding opioid use, have been issued. Although our understanding of the complexities of diabetic neuropathy has substantially evolved over the past decade, the distinct mechanisms underlying neuropathy in type 1 and type 2 diabetes remains unknown. Future discoveries on disease pathogenesis will be crucial to successfully address all aspects of diabetic neuropathy, from prevention to treatment.


Assuntos
Neuropatias Diabéticas/terapia , Analgésicos Opioides/uso terapêutico , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/fisiopatologia , Humanos , Hiperglicemia/complicações , Hiperlipidemias/complicações , Programas de Rastreamento/métodos , Manejo da Dor/métodos , Prevalência , Qualidade de Vida/psicologia , Fatores de Risco , Inibidores da Recaptação de Serotonina e Norepinefrina/uso terapêutico
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