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1.
Artículo en Inglés | MEDLINE | ID: mdl-33431602

RESUMEN

INTRODUCTION: Lockdown measures have a profound effect on many aspects of daily life relevant for diabetes self-management. We assessed whether lockdown measures, in the context of the COVID-19 pandemic, differentially affect perceived stress, body weight, exercise and related this to glycemic control in people with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: We performed a short-term observational cohort study at the Leiden University Medical Center. People with type 1 and type 2 diabetes ≥18 years were eligible to participate. Participants filled out online questionnaires, sent in blood for hemoglobin A1c (HbA1c) analysis and shared data of their flash or continuous glucose sensors. HbA1c during the lockdown was compared with the last known HbA1c before the lockdown. RESULTS: In total, 435 people were included (type 1 diabetes n=280, type 2 diabetes n=155). An increase in perceived stress and anxiety, weight gain and less exercise was observed in both groups. There was improvement in glycemic control in the group with the highest HbA1c tertile (type 1 diabetes: -0.39% (-4.3 mmol/mol) (p<0.0001 and type 2 diabetes: -0.62% (-6.8 mmol/mol) (p=0.0036). Perceived stress was associated with difficulty with glycemic control (p<0.0001). CONCLUSIONS: An increase in perceived stress and anxiety, weight gain and less exercise but no deterioration of glycemic control occurs in both people with relatively well-controlled type 1 and type 2 diabetes during short-term lockdown measures. As perceived stress showed to be associated with glycemic control, this provides opportunities for healthcare professionals to put more emphasis on psychological aspects during diabetes care consultations.


Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 2/sangre , Ejercicio Físico/fisiología , Aumento de Peso/fisiología , Adulto , Anciano , Automonitorización de la Glucosa Sanguínea/psicología , Automonitorización de la Glucosa Sanguínea/tendencias , /psicología , Estudios de Cohortes , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/psicología , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/psicología , Ejercicio Físico/psicología , Femenino , /tendencias , Humanos , Masculino , Persona de Mediana Edad , Servicio Ambulatorio en Hospital/tendencias , Conducta Sedentaria
2.
Nat Commun ; 12(1): 24, 2021 01 05.
Artículo en Inglés | MEDLINE | ID: mdl-33402679

RESUMEN

Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.


Asunto(s)
Anorexia Nerviosa/genética , Glucemia/metabolismo , Intolerancia a la Glucosa/genética , Proteínas Sustrato del Receptor de Insulina/genética , Resistencia a la Insulina/genética , Insulina/sangre , Factores de Transcripción de Tipo Kruppel/genética , Adulto , Anorexia Nerviosa/sangre , Anorexia Nerviosa/etnología , Anorexia Nerviosa/fisiopatología , Grupo de Ascendencia Continental Europea , Ayuno/sangre , Femenino , Expresión Génica , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/etnología , Intolerancia a la Glucosa/fisiopatología , Humanos , Proteínas Sustrato del Receptor de Insulina/sangre , Factores de Transcripción de Tipo Kruppel/sangre , Masculino , Persona de Mediana Edad , Fenotipo , Caracteres Sexuales , Factores Sexuales , Relación Cintura-Cadera
3.
Life Sci ; 264: 118626, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33148417

RESUMEN

AIMS: Circular RNAs (circRNAs) have been shown to play crucial roles in various biological processes and human diseases. However, their exact functions in ischemic stroke remain largely unknown. In this study, we explored the functional role of circRNA HECTD1 (circ-HECTD1) and its underlying mechanism in cerebral ischemia/reperfusion injury. METHODS: Mouse middle cerebral artery occlusion (MCAO) model and oxygen-glucose deprivation (OGD) model in HT22 cells were used to mimic the cerebral ischemia/reperfusion injury. Brain infarct volume, flow cytometry, caspase 3 activity, NF-κB activity, and TUNEL staining were performed to evaluate the function of circ-HECTD1. Luciferase report assay was used to explore the regulatory mechanism. FINDINGS: The results showed that the expression of circ-HECTD1 and tumor necrosis factor receptor-associated factor 3 (TRAF3) was remarkably up-regulated, while miR-133b was down-regulated in oxygen-glucose deprivation (OGD)-induced HT22 cells and mouse middle cerebral artery occlusion (MCAO) model. circ-HECTD1 knockdown relieved OGD-caused neuronal cell death in vitro. Simultaneously, circ-HECTD1 knockdown improved cerebral infarction volume and neuronal apoptosis in MCAO mice. circ-HECTD1 was able to negatively regulate the expression of miR-133b, and TRAF3 is one of the targets of miR-133b. Upregulation of miR-133b inhibited the expression of TRAF3 in OGD-stimulated cells, whereas circ-HECTD1 upregulation reversed this effect. Furthermore, upregulation of miR-133 was able to inhibit OGD-caused cell apoptosis and NF-κB activation, whereas upregulation of circ-HECTD1 attenuated these effects of miR-133b mimics. SIGNIFICANCE: Taken together, circ-HECTD1 knockdown inhibited the expression of TRAF3 by targeting miR-133b, thereby attenuating neuronal injury caused by cerebral ischemia.


Asunto(s)
/genética , MicroARNs/genética , Neuronas/patología , ARN Circular/genética , Factor 3 Asociado a Receptor de TNF/genética , Ubiquitina-Proteína Ligasas/genética , Animales , Apoptosis , Glucemia/metabolismo , Encéfalo/patología , Isquemia Encefálica/patología , Caspasa 3/metabolismo , Regulación hacia Abajo , Técnicas de Silenciamiento del Gen , Masculino , Ratones , Ratones Endogámicos C57BL , Arteria Cerebral Media/patología , Neuroprotección , Oxígeno/metabolismo , Daño por Reperfusión/patología
4.
J Stroke Cerebrovasc Dis ; 30(1): 105380, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33166769

RESUMEN

BACKGROUND AND PURPOSE: Brain infarct growth, despite successful reperfusion, decreases the likelihood of good functional outcome after ischemic stroke. In patients undergoing reperfusion, admission glucose is associated with poor outcome but the effect of glucose level on infarct growth is not well studied. MATERIALS AND METHODS: This is a secondary analysis of the DEFUSE 3 trial. The primary predictor was baseline glucose level and the primary outcome is the change of the ischemic core volume from the baseline to 24-hour follow-up imaging (∆core), transformed as a cube root to reduce right skew. We included DEFUSE 3 patients who were randomized to endovascular therapy, had perfusion imaging data at baseline, an MRI at 24 hours, and who achieved TICI 2b or 3. Linear regression models, both unadjusted and adjusted, were fit to the primary outcome and all models included the baseline core volume as a covariate to normalize ∆core. RESULTS: We identified 62 patients who met our inclusion criteria. The mean age was 68.1±13.1 (years), 48.4% (30/62) were men, and the median (IQR) cube root of ∆core was 2.8 (2.0-3.8) mL. There was an association between baseline glucose level and normalized ∆core in unadjusted analysis (beta coefficient 0.010, p = 0.01) and after adjusting for potential confounders (beta coefficient 0.008, p = 0.03). CONCLUSION: In acute ischemic stroke patients with large vessel occlusion undergoing successful endovascular reperfusion, baseline hyperglycemia is associated with infarction growth. Further study is needed to establish potential neuroprotective benefits of aggressive glycemic control prior to and after reperfusion.


Asunto(s)
Glucemia/metabolismo , Infarto Encefálico/terapia , Procedimientos Endovasculares , Hiperglucemia/complicaciones , Reperfusión , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Infarto Encefálico/complicaciones , Infarto Encefálico/diagnóstico por imagen , Procedimientos Endovasculares/efectos adversos , Femenino , Humanos , Hiperglucemia/sangre , Hiperglucemia/diagnóstico , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Reperfusión/efectos adversos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
6.
Nat Rev Endocrinol ; 17(1): 11-30, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33188364

RESUMEN

Initial studies found increased severity of coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in patients with diabetes mellitus. Furthermore, COVID-19 might also predispose infected individuals to hyperglycaemia. Interacting with other risk factors, hyperglycaemia might modulate immune and inflammatory responses, thus predisposing patients to severe COVID-19 and possible lethal outcomes. Angiotensin-converting enzyme 2 (ACE2), which is part of the renin-angiotensin-aldosterone system (RAAS), is the main entry receptor for SARS-CoV-2; although dipeptidyl peptidase 4 (DPP4) might also act as a binding target. Preliminary data, however, do not suggest a notable effect of glucose-lowering DPP4 inhibitors on SARS-CoV-2 susceptibility. Owing to their pharmacological characteristics, sodium-glucose cotransporter 2 (SGLT2) inhibitors might cause adverse effects in patients with COVID-19 and so cannot be recommended. Currently, insulin should be the main approach to the control of acute glycaemia. Most available evidence does not distinguish between the major types of diabetes mellitus and is related to type 2 diabetes mellitus owing to its high prevalence. However, some limited evidence is now available on type 1 diabetes mellitus and COVID-19. Most of these conclusions are preliminary, and further investigation of the optimal management in patients with diabetes mellitus is warranted.


Asunto(s)
/tratamiento farmacológico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/epidemiología , /antagonistas & inhibidores , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Manejo de la Enfermedad , Humanos , Hipoglucemiantes/administración & dosificación , Hipoglucemiantes/metabolismo , Factores de Riesgo
7.
Gene ; 766: 145155, 2021 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-32950634

RESUMEN

Expression of browning genes are lower in both humans and animals with type 2 diabetes (T2D). This study aims at determining effects of long-term nitrate administration on protein and mRNA levels of uncoupling protein 1 (UCP1), peroxisome proliferator activated receptor gamma (PPAR-γ), and PPAR-γ coactivator 1 alpha (PGC1-α) in epididymal adipose tissue (eAT) of rats with T2D. Male Wistar rats were divided into 4 groups (n = 6/group): Control, diabetes, control + nitrate (CN), and diabetes + nitrate (DN). T2D was induced using high fat diet combined with a low-dose of streptozotocin (30 mg/kg body weight). Sodium nitrate was administrated at a dose of 100 mg/L for 6 months in nitrate-treated rats. Fasting serum glucose and insulin concentrations were measured at months 0 (i.e. at start of the protocol), 3, and 6. At month 6, protein and mRNA levels of UCP1, PPAR-γ, and PGC1-α were measured in eAT samples. In addition, tissue concentration of cyclic guanosine monophosphate (cGMP) was measured and histological analyses were done at month 6. In rats with T2D, 6-month administration of nitrate decreased serum glucose and insulin concentrations by 13% and 23%, respectively and increased cGMP level by 85%. Rats with T2D had lower mRNA and protein levels of PPAR-γ (62%, P < 0.0001 and 18%, P = 0.0472), PGC1-α (49%, P = 0.0019 and 21%, P = 0.0482), and UCP1 (35%, P = 0.0613 and 30%, P = 0.0031) in eAT; 6-month nitrate administration restored these decreased levels to near control values. In addition, nitrate increased adipocyte density by 193% and decreased adipocyte area by 53% in rats with T2D. In conclusion, long-term low-dose nitrate administration increased mRNA and protein expressions of browning genes in white adipose tissue of male rats with T2D; these findings partly explain favorable metabolic effects of nitrate administration in diabetes.


Asunto(s)
Adipocitos Marrones/efectos de los fármacos , Tejido Adiposo Pardo/efectos de los fármacos , Tejido Adiposo Blanco/efectos de los fármacos , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 2/genética , Epidídimo/efectos de los fármacos , Nitratos/administración & dosificación , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipocitos Marrones/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Glucemia/metabolismo , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Epidídimo/metabolismo , Glucosa/metabolismo , Insulina/sangre , Masculino , PPAR gamma/genética , PPAR gamma/metabolismo , ARN Mensajero/genética , Ratas , Ratas Wistar , Estreptozocina/farmacología
8.
Eur Rev Med Pharmacol Sci ; 24(24): 13056-13061, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33378058

RESUMEN

OBJECTIVE: Based on the latest epidemic situation and field experience, this study aims to explore the correlation of computed tomography (CT) stages and blood glucose level in patients with novel coronavirus pneumonia (COVID-19). PATIENTS AND METHODS: The clinical data of first and multiple CT imaging re-examination and blood glucose levels from 62 confirmed cases of COVID-19 were collected for a retrospective analysis to determine the correlation between glucose level and CT-based staging. RESULTS: Of the 62 COVID-19 patients, 48 cases of early stage and 14 cases of advanced stage were found in the CT data of the first diagnosis. These 62 cases were currently under follow-up (17-32 days): 18 cases in early stage-resorption stage, 25 cases in early stage-advanced stage-resorption stage, 12 cases in advanced stage-resorption stage, 5 cases in early stage -advanced stage-severe stage-resorption stage, and 2 cases in advanced stage-severe stage-resorption stage. Among them, the CT of 14 patients with advanced stage at the first diagnosis showed multiple stage lesions (advanced stage + early stage) at the same time. Patients presented with statistically significant changes in blood glucose at early stage-resorption stage, early stage-advanced stage-resorption stage, advanced stage-resorption stage, and early stage-advanced stage-severe stage-resorption stage (p<0.05). However, no statistically significant alterations were observed in the glucose level of patients with advanced stage-severe stage-resorption stage (p>0.05). CONCLUSIONS: Alteration of blood glucose is positively correlated with CT-based staging of COVID-19. Blood glucose is of great value in clinical diagnosis of COVID-19 and in determining the stage and prognosis of this disease.


Asunto(s)
Glucemia/metabolismo , Pulmón/diagnóstico por imagen , Adulto , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X
9.
Nat Commun ; 11(1): 6295, 2020 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-33293550

RESUMEN

The central melanocortin system plays a fundamental role in the control of feeding and body weight. Proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (ARC) also regulate overall glucose homeostasis via insulin-dependent and -independent pathways. Here, we report that a subset of ARC POMC neurons innervate the liver via preganglionic parasympathetic acetylcholine (ACh) neurons in the dorsal motor nucleus of the vagus (DMV). Optogenetic stimulation of this liver-projecting melanocortinergic pathway elevates blood glucose levels that is associated with increased expression of hepatic gluconeogenic enzymes in female and male mice. Pharmacological blockade and knockdown of the melanocortin-4 receptor gene in the DMV abolish this stimulation-induced effect. Activation of melanocortin-4 receptors inhibits DMV cholinergic neurons and optogenetic inhibition of liver-projecting parasympathetic cholinergic fibers increases blood glucose levels. This elevated blood glucose is not due to altered pancreatic hormone release. Interestingly, insulin-induced hypoglycemia increases ARC POMC neuron activity. Hence, this liver-projecting melanocortinergic circuit that we identified may play a critical role in the counterregulatory response to hypoglycemia.


Asunto(s)
Glucemia/metabolismo , Hipoglucemia/etiología , Hígado/inervación , Proopiomelanocortina/metabolismo , Nervio Vago/metabolismo , Acetilcolina/metabolismo , Potenciales de Acción/fisiología , Animales , Núcleo Arqueado del Hipotálamo/citología , Núcleo Arqueado del Hipotálamo/metabolismo , Glucemia/análisis , Neuronas Colinérgicas/metabolismo , Corticosterona/sangre , Corticosterona/metabolismo , Modelos Animales de Enfermedad , Vías Eferentes/fisiología , Femenino , Técnicas de Silenciamiento del Gen , Glucagón/sangre , Glucagón/metabolismo , Gluconeogénesis/genética , Humanos , Hipoglucemia/sangre , Hipoglucemia/diagnóstico , Insulina/sangre , Insulina/metabolismo , Hígado/enzimología , Masculino , Ratones , Optogenética , ARN Mensajero/metabolismo , Receptor de Melanocortina Tipo 4/antagonistas & inhibidores , Receptor de Melanocortina Tipo 4/genética , Receptor de Melanocortina Tipo 4/metabolismo , Regulación hacia Arriba , Nervio Vago/citología
10.
Ter Arkh ; 92(10): 54-62, 2020 Nov 24.
Artículo en Ruso | MEDLINE | ID: mdl-33346480

RESUMEN

AIM: To investigate the link between the hypoglycemia (registrated accurately by the professional Continuous Glucose Monitoring CGM; severe hypoglycemia at home) and the hetero-/homozygote carriage of single nucleotide polymorphisms (SNP) of cytochrome systems geneCYP2C9(rs1799853CYP2C9*2 иrs1057910CYP2C9*3) at the patients with Type 2 Diabetes Mellitus (T2DM) used sulphonylurea (SU). MATERIALS AND METHODS: In Study Case-Control 120 T2DM-SU-patients genotyped by SNPs of geneCYP2C9(using PCR-RT) had been done the professional CGM (System iPro2, Medtronic) recorded Time in Range of Hypoglycemia (TIR-HYPO), level of Minimal CGM-hypoglycemia (MinGl) and standard CGM-parameters of Glycemic Variability. Severe hypoglycemia at home was recorded from visit to visit. The odds ratio (OR) of metabolic disturbances had been assessed for carriage SNPs in comparison with wide alleles. RESULTS: The Study established that carriage of SNPsrs1799853andrs1057910geneCYP2C9at T2DM-SU-patients associated with rising of Glycemic Variability and frequency of CGM-hypoglycemia (MinGl decreasing, increasing of TIR-HYPO and number of Glycemia Excursion 4 mmol/L/h), as well as increasing severe hypoglycemia at home (p0.05). Thus, OR at the carriage ofrs1799853andrs1057910respectively equaled: for CGM-hypoglycemia 7.78 (3.0220.01) and 5.80 (0.23145.87); number of Glycemia Excursion 4 mmol/L/h 5.76 (2.2914.43) and 4.44 (1.4313.76); MinGl3.9 mmol/L 4.39 (1.7910.75) and 6.26 (1.8421.30); CV40% (vs30%) 3.63 (1.0412.62) and 15.22 (0.59393.94);p0.05. CONCLUSION: At the real clinical practice the assessment of carriage of SNPs of geneCYP2C9before inclusion of SU to glucose-lowering scheme of T2DM-therapy it necessary to carry out for the detecting patients with a higher risk of hypoglycemia and rising of Glycemic Variability.


Asunto(s)
Diabetes Mellitus Tipo 2 , Hipoglucemia , Hipoglucemiantes/efectos adversos , Glucemia/metabolismo , Automonitorización de la Glucosa Sanguínea , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/genética , Hemoglobina A Glucada/análisis , Humanos , Hipoglucemia/inducido químicamente , Hipoglucemia/genética , Hipoglucemiantes/uso terapéutico , Farmacogenética
11.
Int J Nanomedicine ; 15: 9265-9282, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33262587

RESUMEN

Background: Diabetic foot ulcer is an intractable complication of diabetes, characterized by the disturbed inflammatory and proliferative phases of wound healing. Sesamol, a phenolic compound, has been known for its powerful antioxidant, anti-inflammatory, anti-hyperglycaemic and wound healing properties. The aim of the present study was to develop a sesamol nano formulation and to study its effect on the various phases of the wound healing process in diabetic foot condition. Methods: Sesamol-PLGA (SM-PLGA) nanosuspension was developed  using nanoprecipitation method. TEM, in vitro drug release assay and in vivo pharmacokinetic studies were performed for the optimised formulation. Diabetic foot ulcer (DFU) in high fat diet (HFD)-fed streptozotocin-induced type-II diabetic animal model was used to assess the SM-PLGA nanosuspension efficacy. SM-PLGA nanosuspension was administered by oral route. TNF-α levels were estimated using ELISA and Western blot analysis was performed to assess the effect on the expression of HSP-27, ERK, PDGF-B and VEGF in wound tissue. Wound re-epithelization, fibroblast migration, collagen deposition and inflammatory cell infiltration were assessed by H&E and Masson's trichrome staining. Effect on angiogenesis was assessed by CD-31 IHC staining in wound sections. Results: The optimized SM-PLGA nanosuspension had an average particle size of <300 nm, PDI<0.200 with spherical shaped particles. Approximately 80% of the drug was released over a period of 60 h in in vitro assay. Half-life of the formulation was found to be 13.947 ± 0.596 h. SM-PLGA nanosuspension treatment decreased TNF-α levels in wound tissue and accelerated the collagen deposition. Whereas, HSP-27, ERK, PDGF-B and VEGF expression increased and improved new blood vessels' development. Rapid re-epithelization, fibroblast migration, collagen deposition and reduced inflammatory cell infiltration at the wound site were also observed. Conclusion: Results indicate that sesamol-PLGA nanosuspension significantly promotes the acceleration of wound healing in diabetic foot ulcers by restoring the altered wound healing process in diabetic condition.


Asunto(s)
Benzodioxoles/uso terapéutico , Pie Diabético/tratamiento farmacológico , Nanopartículas/química , Fenoles/uso terapéutico , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/química , Cicatrización de Heridas/efectos de los fármacos , Animales , Benzodioxoles/sangre , Benzodioxoles/farmacocinética , Benzodioxoles/farmacología , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Rastreo Diferencial de Calorimetría , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/patología , Pie Diabético/sangre , Pie Diabético/patología , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Liberación de Fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Prueba de Tolerancia a la Glucosa , Proteínas de Choque Térmico HSP27/metabolismo , Masculino , Neovascularización Fisiológica/efectos de los fármacos , Fenoles/sangre , Fenoles/farmacocinética , Fenoles/farmacología , Factor de Crecimiento Derivado de Plaquetas , Alcohol Polivinílico/química , Ratas Wistar , Espectroscopía Infrarroja por Transformada de Fourier , Estreptozocina/farmacología , Suspensiones , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo
12.
PLoS One ; 15(12): e0243192, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33270719

RESUMEN

OBJECTIVE: To evaluate the role of fasting blood glucose (FBG) to minimise the use of the oral glucose tolerance test in pregnancy (POGTT) for the diagnosis of gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS: We analysed the POGTTs of 26,242 pregnant women in Queensland, Australia, performed between 1 January 2015 and 30 June 2015. A receiver operator characteristics (ROC) assessment was undertaken to indicate the FBG level that most effectively identified women at low risk of an abnormal result. RESULTS: There were 3,946 (15.0%) patients having GDM with 2,262 (8.6%) having FBG ≥ 5.1mmol/l. The ROC identified FBG levels >4.6mmol/l having the best specificity (77%) and sensitivity (54%) for elevated 1 and/or 2hr BGLs. There were 19,321 (73.7%) women having FBG < 4.7mmol/l with a prevalence of GDM of 4.0%, less than 1/3rd the overall rate. Only 4,638 (17.7%) women having FBGs from 4.7-5.0mmol/l would require further evaluation to confirm or exclude the diagnosis. CONCLUSION: This contemporary study of women across the state of Queensland, Australia suggests the FBG can be used effectively to define glucose tolerance in pregnancy, minimising their contact with pathology laboratories and potential exposure to the corona virus. This analysis, used in conjunction with outcome data from the HAPO study, provides reassurance to women and their health professionals that FBG < 4.7mmol/l has both a low rate of abnormal glucose tolerance and minimal adverse pregnancy-associated complications.


Asunto(s)
Glucemia/análisis , Diabetes Gestacional/sangre , Adulto , Glucemia/metabolismo , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiología , Ayuno/metabolismo , Femenino , Prueba de Tolerancia a la Glucosa/métodos , Prueba de Tolerancia a la Glucosa/normas , Humanos , Embarazo , Queensland
13.
Medicine (Baltimore) ; 99(46): e23039, 2020 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-33181668

RESUMEN

BACKGROUND: With the rapid development of modern society, people's dietary structure has been changing accordingly. Diets high in salt, fat, and sugar have led to an increase in the incidence of diabetes year by year, posing a great threat to human health. More than 90% of diabetic patients have type 2 diabetes mellitus (T2DM). It is currently believed that the onset of T2DM is mainly related to factors such as genetics, insulin resistance, impaired insulin cell function, and obesity. The main mechanisms are as follows:The dominant flora of normal intestinal tract is mainly anaerobic bacteria which are beneficial to the human body. Under certain conditions, when intestinal flora is maladjusted, harmful bacteria and opportunistic bacteria become the dominant intestinal bacteria, resulting in metabolic disorders. Ingestion of probiotics can correct the imbalance of intestinal flora, and then, have a therapeutic effect on T2DM. Therefore, we designed this study to evaluate the effects of probiotics on blood glucose control and intestinal dominant flora in patients with T2DM. METHODS: The retrieval period of meta-analysis literature is set from January 1, 1990 to September 2020. We will mainly search five English electronic databases, including Cochrane Library, Pubmed, Excerpt Medical Database (EMBASE), Science Direct and Web of Science, and search the following four Chinese databases: China Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), China Science Journal Database (VIP), Wanfang Database, and so on. At the same time, the two reviewers will independently conduct research selection, data extraction and deviation risk assessment, and use Review Manager 5.3 software provided by the Cochrane Collaboration for meta-analysis and heterogeneity assessment. RESULTS: This study will demonstrate an evidence-based review of probiotics on glycemic control and intestinal dominant flora in patients with type 2 diabetes mellitus. CONCLUSION: This study can be used to evaluate the efficacy and safety of probiotics on glycemic control and intestinal dominant flora in patients with T2DM. REGISTRATION NUMBER:: is INPLASY202090104.


Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 2/terapia , Microbioma Gastrointestinal , Probióticos/uso terapéutico , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/microbiología , Humanos , Metaanálisis como Asunto , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Resultado del Tratamiento
14.
Medicine (Baltimore) ; 99(46): e23130, 2020 Nov 13.
Artículo en Inglés | MEDLINE | ID: mdl-33181684

RESUMEN

BACKGROUND: Polycystic ovary syndrome (PCOS) is one of the common gynecological endocrine system diseases. It is characterized by excessive androgen, rare or anovulation, and polycystic ovary morphology. Coenzyme Q10 (CoQ10) is a fat-soluble natural vitamin, which has a continuous oxidation-reduction cycle and is an effective antioxidant that can protect ovaries from oxidative damage. This study aims to systematically summarize and analyze the scientific literatures on glucose metabolism index, lipid profiles, inflammatory factor, and sex hormone level of PCOS patients treated with CoQ10 to provide a reference basis for clinical treatment. METHODS: We will retrieve the following electronic databases from the built-in until March 2021: Cochrane Library, PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), Clinical Trials. gov, Chinese Scientific Journal Database (VIP), and Wang-fang database. Two reviewers will independently scan the articles searched, de-duplication, filtering, quality assessment. Differences will be resolved by discussion between the 2 reviewers or by a third reviewers. All analyses were systematic to evaluate interventions based on the Cochrane handbook. Meta-analysis and/or subgroup analysis will be performed on the basis of the included studies. DISCUSSION: This review will be to investigate the efficacy of CoQ10 supplementation on glucose metabolism, lipid profiles, and biomarkers of inflammation in women with PCOS and provide a high-quality synthesis to assess whether CoQ10 is an effective and safe intervention for PCOS. The results of the analysis will be published in a scientific journal after peer-review. SYSTEMATIC REVIEW REGISTRATION: INPLASY 2020100013.


Asunto(s)
Glucemia/metabolismo , Inflamación/sangre , Lípidos , Síndrome del Ovario Poliquístico , Ubiquinona/análogos & derivados , Biomarcadores/sangre , Femenino , Humanos , Lípidos/sangre , Lípidos/clasificación , Metaanálisis como Asunto , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/metabolismo , Proyectos de Investigación , Revisiones Sistemáticas como Asunto , Resultado del Tratamiento , Ubiquinona/farmacología , Vitaminas/farmacología
15.
Eur J Prev Cardiol ; 27(2_suppl): 27-34, 2020 12.
Artículo en Inglés | MEDLINE | ID: mdl-33238738

RESUMEN

Cardiovascular and non-cardiovascular comorbidities are frequently observed in heart failure patients, complicating the therapeutic management and leading to poor prognosis. The prompt recognition of associated comorbid conditions is of great importance to optimize the clinical management, the follow-up, and the treatment of patients affected by chronic heart failure. Anaemia and iron deficiency are commonly reported in all heart failure forms, have a multifactorial aetiology and are responsible for reduced exercise tolerance, impaired quality of life, and poor long-term prognosis. Diabetes mellitus is highly prevalent in heart failure and a poor glycaemic control is associated with worst outcome. Two specific heart failure forms are usually observed in diabetic patients: an ischaemic cardiomyopathy or a typical diabetic cardiomyopathy. The implementation of use of sodium-glucose cotransporter-2 inhibitors will much improve in the near future the long-term prognosis of patients affected by heart failure and diabetes. Among cardiovascular comorbidities, atrial fibrillation is the most common arrhythmic disease of heart failure patients and it is still not clear whether its presence should be considered as a prognostic indicator or as a marker of advanced disease. The aim of the present review was to explore the clinical and prognostic impact of anaemia and iron deficiency, diabetes mellitus, and atrial fibrillation in patients affected by chronic heart failure.


Asunto(s)
Anemia Ferropénica/epidemiología , Fibrilación Atrial/epidemiología , Diabetes Mellitus/epidemiología , Insuficiencia Cardíaca/epidemiología , Anemia Ferropénica/sangre , Anemia Ferropénica/diagnóstico , Anemia Ferropénica/terapia , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/terapia , Biomarcadores/sangre , Glucemia/metabolismo , Comorbilidad , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/terapia , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Hemoglobinas/metabolismo , Humanos , Hierro/sangre , Pronóstico , Medición de Riesgo
16.
PLoS One ; 15(11): e0242423, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33206702

RESUMEN

BACKGROUND: The aim of this study was to evaluate whether soluble frizzled-related protein 4 (sFRP4) concentration in the first trimester of pregnancy is individually, or in combination with Leptin, Chemerin and/or Adiponectin, associated with the development of gestational diabetes (GDM). METHODS: In a nested case-control study, 50 women with GDM who spontaneously conceived and delivered a live-born infant were matched with a total of 100 uncomplicated singleton control pregnancies based on body mass index (± 2 kg/m2), gestational age at sampling (exact day) and maternal age (± 2 years). In serum samples, obtained between 70-90 days gestational age, sFRP4, Chemerin, Leptin and Adiponectin concentrations were determined by ELISA. Statistical comparisons were performed using univariate and multi-variate logistic regression analysis after logarithmic transformation of the concentrations. Discrimination of the models was assessed by the area under the curve (AUC). RESULTS: First trimester sFRP4 concentrations were significantly increased in GDM cases (2.04 vs 1.93 ng/ml; p<0.05), just as Chemerin (3.19 vs 3.15 ng/ml; p<0.05) and Leptin (1.44 vs 1.32 ng/ml; p<0.01). Adiponectin concentrations were significantly decreased (2.83 vs 2.94 ng/ml; p<0.01) in GDM cases. Further analysis only showed a weak, though significant, correlation of sFRP4 with Chemerin (R2 = 0.124; p<0.001) and Leptin (R2 = 0.145; p<0.001), and Chemerin with Leptin (R2 = 0.282; p<0.001) in the control group. In a multivariate logistic regression model of these four markers, only Adiponectin showed to be significantly associated with GDM (odds ratio 0.12, 95%CI 0.02-0.68). The AUC of this model was 0.699 (95%CI 0.605-0.793). CONCLUSION: In the first trimester of pregnancy, a multi-marker model with sFRP4, Leptin, Chemerin and Adiponectin is associated with the development of GDM. Therefore, this panel seems to be an interesting candidate to further evaluate for prediction of GDM in a prospective study.


Asunto(s)
Diabetes Gestacional/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Adipoquinas/análisis , Adipoquinas/sangre , Adiponectina/análisis , Adiponectina/sangre , Adulto , Área Bajo la Curva , Biomarcadores/sangre , Glucemia/metabolismo , Índice de Masa Corporal , Estudios de Casos y Controles , Quimiocinas/análisis , Quimiocinas/sangre , Quimiocinas/metabolismo , Diabetes Gestacional/fisiopatología , Femenino , Humanos , Leptina/análisis , Leptina/sangre , Edad Materna , Países Bajos , Oportunidad Relativa , Embarazo , Primer Trimestre del Embarazo/sangre , Estudios Prospectivos , Proteínas Proto-Oncogénicas/sangre , Proteínas Proto-Oncogénicas/fisiología , Curva ROC
17.
Ann Afr Med ; 19(4): 230-236, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33243945

RESUMEN

Background: Sleep disturbance is a major health issue among people with type 2 diabetes mellitus (T2DM). The Pittsburgh Sleep Quality Index (PSQI) has been the most widely used instrument to measure subjective sleep disturbance. Aim: The aim of this study was to determine the impact of sleeping factor structure of the PSQI as potential predictor for glycosylated hemoglobin A1c (HbA1C) among people living with T2DM in the Turkish community to facilitate its use in the clinical practice and research. Subjects and Methods: This is a cross-sectional study and participants were between the age group of 25 and 65 years old who visited the diabetes and endocrinology department of Mega Medipol University Teaching Hospital, Istanbul. The PSQI was conducted on 871 patients with T2DM. Good sleep quality was defined as PSQI score <5. Multivariate logistic regression analysis was used to estimate the associated risk factors for the T2DM. Results: The current study showed significant differences between male and female patients with respect to their age in years, body mass index (BMI) (kg/m2), physical activity, smoking habit, sheesha smoking, income, family history of metabolic syndrome, coronary heart disease (CHD), and PSQI. The results revealed significant differences between HbA1c ≤7 and females and HbA1c >7 T2DM patients with respect to gender, BMI (kg/m2), CHD, and PSQI. The study demonstrated significant differences between sleeping categories PSQI as good, average, and poor sleeping among T2DM patients with respect to age and gender. Meanwhile, significant differences were reported between sleeping categories among T2DM patients with respect to their: number of sleeping hours, wake-up time, sleeping time, HbA1c, fasting blood glucose, uric acid, and systolic and diastolic blood pressure. This study showed very strong statistically significant correlations between low HbA1c and poor sleep quality in patients with T2DM patients, including subjective sleep quality r = 0.763, sleep latency r = 0.327, sleep duration r = 0.472, habitual sleep efficiency r = 0.575, sleep disturbances r = 0.564, use of sleep medication r = 0.728, and daytime dysfunction r = 0.734. Multivariate stepwise logistic regression analysis revealed that Vitamin D (mmol/L) (P < 0.001), HbA1c (P < 0.001), duration of DM (P < 0.001), uric acid (mmol/L) (P < 0.001), systolic blood pressure mmHg (P = 0.006), diastolic blood pressure mmHg (P = 0.015), and BMI (P = 0.024) were considered at higher risk as the predictors for sleeping quality among T2DM patients. Conclusion: The results suggest a strong positive correlation between PSQI with HbA1c levels, systolic and diastolic blood pressure, age, BMI, among type 2 diabetic patients. This study ascertains that poor sleep quality may be due to elevated level of HbA1c, metabolic syndrome, diabetes, obesity, and/or hypertension.


Asunto(s)
Diabetes Mellitus Tipo 2/complicaciones , Hemoglobina A Glucada/metabolismo , Trastornos del Sueño-Vigilia/sangre , Trastornos del Sueño-Vigilia/complicaciones , Sueño/fisiología , Adulto , Factores de Edad , Anciano , Glucemia/análisis , Glucemia/metabolismo , Presión Sanguínea , Índice de Masa Corporal , Estudios Transversales , Diabetes Mellitus Tipo 2/sangre , Ejercicio Físico , Femenino , Humanos , Hipertensión/complicaciones , Masculino , Persona de Mediana Edad , Obesidad/complicaciones , Factores de Riesgo , Apnea Obstructiva del Sueño/sangre , Apnea Obstructiva del Sueño/complicaciones
18.
BMC Med Genet ; 21(1): 234, 2020 11 23.
Artículo en Inglés | MEDLINE | ID: mdl-33228548

RESUMEN

BACKGROUND: Autosomal dominant familial hypercholesterolemia (ADH; MIM#143890) is one of the most common monogenic disorders characterized by elevated circulatory LDL cholesterol. Initial studies in humans with ADH identified a potential relationship with variants of the gene encoding signal transducing adaptor family member protein 1 (STAP1; MIM#604298). However, subsequent studies have been contradictory. In this study, mice lacking global Stap1 expression (Stap1-/-) were characterized under standard chow and a 42% kcal western diet (WD). METHODS: Mice were studied for changes in different metabolic parameters before and after a 16-week WD regime. Growth curves, body fats, circulatory lipids, parameters of glucose homeostasis, and liver architecture were studied for comparisons. RESULTS: Surprisingly, Stap1-/- mice fed the 16-week WD demonstrated no marked differences in any of the metabolic parameters compared to Stap1+/+ mice. Furthermore, hepatic architecture and cholesterol content in FPLC-isolated lipoprotein fractions also remained comparable to wild-type mice. CONCLUSION: These results strongly suggest that STAP1 does not alter lipid levels, that a western diet did not exacerbate a lipid disorder in Stap1 deficient mice and support the contention that it is not causative for hyperlipidemia in ADH patients. These results support other published studies also questioning the role of this locus in human hypercholesterolemia.


Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/genética , LDL-Colesterol/sangre , Dieta Occidental , Triglicéridos/sangre , Proteínas Adaptadoras Transductoras de Señales/deficiencia , Tejido Adiposo/metabolismo , Animales , Glucemia/metabolismo , Femenino , Expresión Génica , Humanos , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/metabolismo , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados
19.
PLoS One ; 15(11): e0242360, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33253307

RESUMEN

AIM: Subclasses of different glycaemic disturbances could explain the variation in characteristics of individuals with type 2 diabetes (T2D). We aimed to examine the association between subgroups based on their glucose curves during a five-point mixed-meal tolerance test (MMT) and metabolic traits at baseline and glycaemic deterioration in individuals with T2D. METHODS: The study included 787 individuals with newly diagnosed T2D from the Diabetes Research on Patient Stratification (IMI-DIRECT) Study. Latent class trajectory analysis (LCTA) was used to identify distinct glucose curve subgroups during a five-point MMT. Using general linear models, these subgroups were associated with metabolic traits at baseline and after 18 months of follow up, adjusted for potential confounders. RESULTS: At baseline, we identified three glucose curve subgroups, labelled in order of increasing glucose peak levels as subgroup 1-3. Individuals in subgroup 2 and 3 were more likely to have higher levels of HbA1c, triglycerides and BMI at baseline, compared to those in subgroup 1. At 18 months (n = 651), the beta coefficients (95% CI) for change in HbA1c (mmol/mol) increased across subgroups with 0.37 (-0.18-1.92) for subgroup 2 and 1.88 (-0.08-3.85) for subgroup 3, relative to subgroup 1. The same trend was observed for change in levels of triglycerides and fasting glucose. CONCLUSIONS: Different glycaemic profiles with different metabolic traits and different degrees of subsequent glycaemic deterioration can be identified using data from a frequently sampled mixed-meal tolerance test in individuals with T2D. Subgroups with the highest peaks had greater metabolic risk.


Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Anciano , Glucemia/análisis , Diabetes Mellitus Tipo 2/sangre , Ayuno/sangre , Ayuno/metabolismo , Femenino , Estudios de Seguimiento , Hemoglobina A Glucada/análisis , Hemoglobina A Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Triglicéridos/sangre , Triglicéridos/metabolismo
20.
Proc Natl Acad Sci U S A ; 117(47): 29512-29517, 2020 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-33177238

RESUMEN

Reduced ß-cell function and insulin deficiency are hallmarks of diabetes mellitus, which is often accompanied by the malfunction of glucagon-secreting α-cells. While insulin therapy has been developed to treat insulin deficiency, the on-demand supplementation of glucagon for acute hypoglycemia treatment remains inadequate. Here, we describe a transdermal patch that mimics the inherent counterregulatory effects of ß-cells and α-cells for blood glucose management by dynamically releasing insulin or glucagon. The two modules share a copolymerized matrix but comprise different ratios of the key monomers to be "dually responsive" to both hyper- and hypoglycemic conditions. In a type 1 diabetic mouse model, the hybrid patch effectively controls hyperglycemia while minimizing the occurrence of hypoglycemia in the setting of insulin therapy with simulated delayed meal or insulin overdose.


Asunto(s)
Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Tipo 1/tratamiento farmacológico , Sistemas de Liberación de Medicamentos/métodos , Glucagón/administración & dosificación , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Animales , Glucemia/análisis , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Preparaciones de Acción Retardada/administración & dosificación , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/diagnóstico , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/inducido químicamente , Diabetes Mellitus Tipo 1/diagnóstico , Combinación de Medicamentos , Composición de Medicamentos/métodos , Liberación de Fármacos , Sobredosis de Droga/prevención & control , Glucagón/química , Glucagón/farmacocinética , Humanos , Hipoglucemiantes/química , Hipoglucemiantes/farmacocinética , Insulina/química , Insulina/farmacocinética , Masculino , Ratones , Polimerizacion , Solubilidad , Estreptozocina , Parche Transdérmico
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