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1.
Medicine (Baltimore) ; 99(40): e22337, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019410

RESUMO

At present, glycated hemoglobin (HbA1c) and glycated albumin (GA) are used to evaluate glycemic control in diabetic patients, but they cannot reflect insulin deficiency and/or insulin resistance.We investigated the feasibility of using estimated average glucose to fasting plasma glucose ratio (eAG/fPG ratio) to estimate insulin resistance in young adult diabetes. A total of 387 patients with type 2 diabetes were included and were stratified into 2 groups based on median values of the glycemic index ratio: the GA/A1c ratio <2.09 (n = 91) and ≥2.09 (n = 296); the eAG/fPG ratio <1.69 (n = 155) and ≥1.69 (n = 232). HbA1c, GA, fructosamine, insulin, and C-peptide levels were measured. The ratio of GA to HbA1c was calculated, and the homeostasis model assessment of ß-cell function and insulin resistance were determined. The homeostasis model assessment of insulin resistance level was significantly associated with the eAG/fPG ratio, but not with the ratio of GA to HbA1c, GA, HbA1c, and fructosamine levels. The ratio of estimated average glucose to fasting plasma glucose level correlates with insulin resistance in young adult diabetes.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/sangue , Jejum/metabolismo , Resistência à Insulina/fisiologia , Adolescente , Adulto , Peptídeo C/sangue , Criança , Feminino , Frutosamina/sangue , Hemoglobina A Glicada/análise , Índice Glicêmico , Humanos , Insulina/sangue , Masculino , Albumina Sérica/análise , Adulto Jovem
2.
Medicine (Baltimore) ; 99(35): e21654, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871878

RESUMO

The aim of this study is to investigate the levels of 25(OH)D, inflammation markers and glucose and fat metabolism indexes in pregnant women with Gestational diabetes mellitus (GDM).One hundred and ten cases GDM and 100 cases healthy pregnant women in the First People's Hospital of Lianyungang City from October 2016 to December 2018 were recruited for this observational cross-sectional study. Each participant's anthropometric and demographic data was recorded. Blood samples were collected and analyzed to determine the levels of 25(OH)D, high sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), fasting blood glucose, fasting blood insulin, hemoglobin A1c (HbA1c), homeostasis model assessment of insulin resistance (HOMA-IR), cholesterol and triglycerides.Inflammatory markers and glucose and fat metabolism indexes were all significantly higher in the GDM group than that in the control group, while Serum 25(OH)D level in the GDM group was significantly lower. Serum 25(OH)D levels were negatively correlated with hs-CRP, while not with TNF-α. Furthermore, Serum 25(OH)D, hs-CRP and TNF-α levels were all associated with increased risk of developing GDM.Nowadays, the reports on the association between 25(OH)D level and GDM were controversial. Our results are consistent with the view that there was association between 25(OH)D level and GDM, and expand the literature by showing the roles of 25(OH)D, inflammation markers as well as glucose and fat metabolism indexes in the risk of developing GDM in the pregnant women with the low overall levels of 25(OH)D before delivery. This broadens our knowledge on the pathophysiology of GDM, which may be helpful in prevention and treatment of GDM.


Assuntos
Glicemia/metabolismo , Diabetes Gestacional/sangue , Vitamina D/análogos & derivados , Adulto , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , China , Colesterol/sangue , Estudos Transversais , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Insulina/sangue , Resistência à Insulina , Gravidez , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/sangue , Vitamina D/sangue
3.
Open Heart ; 7(2)2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32938758

RESUMO

Risk factors for COVID-19 patients with poorer outcomes include pre-existing conditions: obesity, type 2 diabetes mellitus, cardiovascular disease (CVD), heart failure, hypertension, low oxygen saturation capacity, cancer, elevated: ferritin, C reactive protein (CRP) and D-dimer. A common denominator, hyperinsulinaemia, provides a plausible mechanism of action, underlying CVD, hypertension and strokes, all conditions typified with thrombi. The underlying science provides a theoretical management algorithm for the frontline practitioners.Vitamin D activation requires magnesium. Hyperinsulinaemia promotes: magnesium depletion via increased renal excretion, reduced intracellular levels, lowers vitamin D status via sequestration into adipocytes and hydroxylation activation inhibition. Hyperinsulinaemia mediates thrombi development via: fibrinolysis inhibition, anticoagulation production dysregulation, increasing reactive oxygen species, decreased antioxidant capacity via nicotinamide adenine dinucleotide depletion, haem oxidation and catabolism, producing carbon monoxide, increasing deep vein thrombosis risk and pulmonary emboli. Increased haem-synthesis demand upregulates carbon dioxide production, decreasing oxygen saturation capacity. Hyperinsulinaemia decreases cholesterol sulfurylation to cholesterol sulfate, as low vitamin D regulation due to magnesium depletion and/or vitamin D sequestration and/or diminished activation capacity decreases sulfotransferase enzyme SULT2B1b activity, consequently decreasing plasma membrane negative charge between red blood cells, platelets and endothelial cells, thus increasing agglutination and thrombosis.Patients with COVID-19 admitted with hyperglycaemia and/or hyperinsulinaemia should be placed on a restricted refined carbohydrate diet, with limited use of intravenous dextrose solutions. Degree/level of restriction is determined by serial testing of blood glucose, insulin and ketones. Supplemental magnesium, vitamin D and zinc should be administered. By implementing refined carbohydrate restriction, three primary risk factors, hyperinsulinaemia, hyperglycaemia and hypertension, that increase inflammation, coagulation and thrombosis risk are rapidly managed.


Assuntos
Infecções por Coronavirus/terapia , Dieta com Restrição de Carboidratos , Suplementos Nutricionais , Hiperinsulinismo/terapia , Insulina/sangue , Magnésio/uso terapêutico , Pneumonia Viral/terapia , Trombose/terapia , Vitamina D/uso terapêutico , Betacoronavirus/patogenicidade , Biomarcadores/sangue , Glicemia/metabolismo , Infecções por Coronavirus/sangue , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Suplementos Nutricionais/efeitos adversos , Interações Hospedeiro-Patógeno , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/epidemiologia , Cetonas/sangue , Magnésio/sangue , Pandemias , Pneumonia Viral/sangue , Pneumonia Viral/epidemiologia , Pneumonia Viral/virologia , Prognóstico , Fatores de Risco , Trombose/sangue , Trombose/epidemiologia , Trombose/virologia , Vitamina D/sangue , Zinco/uso terapêutico
5.
Medicine (Baltimore) ; 99(34): e21894, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846852

RESUMO

BACKGROUND: At present, metformin is mainly used in the treatment of type 2 diabetes mellitus (T2DM). When the therapeutic effect is achieved, there are side effects and secondary failure will occur if taken for a long time. It is of great significance to actively explore the clinical scheme of reducing drug use while ensuring the therapeutic effect of T2DM. OBJECTIVE: To evaluate the feasibility of Chinese massage (CM) in the treatment of T2DM. METHODS: Literature retrieval is divided into 2 aspects: Electronic Retrieval and Personal Check. We will search PubMed, EMBASE, CNKI, Cochrane Central, which were registered in international clinical trials registry platform systems, select all eligible studies published before November 2, 2019, and use Personal Check method to retrieve papers, conference papers, ongoing experiments, internal reports, and so on. With fasting blood glucose, 2-hour fasting blood glucose, glycosylated hemoglobin, and insulin index as the main observation indexes, we also pay attention to traditional Chinese medicine syndrome score scale, insulin resisting index, body mass index , serum total cholesterol, Curative effect and the occurrence of all adverse reactions in drug treatment.Of the research group 2 researchers respective selected literature, extracted data, and evaluated the risk of bias. After that we used Revman 5.7 and Stata 12.1 statistical software for meta-analysis. RESULTS: A total of 769 subjects were included in 10 studies for meta-analysis. Compared with metformin hydrochloride tablets, CM plus baseline treatment can reduce fasting plasma glucose (weighted mean difference [WMD] = -0.33, 95% confidence interval [CI] [-0.54, -0.13], Z = 3.15, P = .002), 2 hours postprandial blood glucose (WMD = -0.52, 95% CI [-0.70, -0.34), Z = 5.66, P < .00001], hemoglobin A1c (WMD = 0.12, 95% CI [0.04, 0.20], Z = 2.94, P = .003), fasting insulin (WMD = -3.59, 95% CI [-5.56, -1.42], Z = 10.29,P < .00001), traditional Chinese medicine syndrome score scale (WMD = -4.55, 95% CI [-7.58, -1.51], Z = 2.94, P = .003),homeostasis model assessment of insulin resistance (WMD = -1.76, 95% CI [-2.25, -1.27), Z = 7.08, P < .00001),body mass index (WMD = -1.28, 95% CI [-1.65, -0.92], Z = 6.91, P < .00001), serum total cholesterol (WMD = -1.01, 95% CI [-1.14, -0.83], Z = 15.51, P < .00001), meanwhile, the effective rate was increased (risk ratio [RR] = 1.31, 95% CI [1.21, 1.42], Z = 6.57, P < .00001). CONCLUSION: CM combined with metformin hydrochloride tablet has a synergistic effect. It can not only be used as an auxiliary treatment of T2DM, but also as an important reference way of reducing drug treatment of T2DM, improving Clinical Efficacy and reducing adverse reactions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020158839.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Hipoglicemiantes/uso terapêutico , Massagem/métodos , Metformina/uso terapêutico , Adulto , Idoso , Glicemia/análise , Estudos de Casos e Controles , China/epidemiologia , Terapia Combinada/métodos , Sinergismo Farmacológico , Jejum/sangue , Estudos de Viabilidade , Hemoglobina A Glicada/análise , Humanos , Hipoglicemiantes/efeitos adversos , Insulina/sangue , Resistência à Insulina , Massagem/tendências , Metformina/efeitos adversos , Pessoa de Meia-Idade
6.
PLoS One ; 15(8): e0235404, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32785222

RESUMO

OBJECTIVE: To study the role of selected serum inflammatory cytokines and berberine in the insulin signaling pathway among women with polycystic ovary syndrome (PCOS). METHODS: Selected serum inflammatory cytokines were analyzed in the particle cells, which were interfered by berberine, from 78 infertile women who were to be treated with In Vitro Fertilization (IVF) /Intracytoplasmic Sperm Injection-Embryo Transfer (icsi-et). Among them, 49 patients had PCOS infertility, and 29 were non-PCOS patients whose infertility resulted from fallopian tube and male factors. The elisa method was used to detect the changes in the expression levels of inflammatory factors in the cells. The correlations between the serum inflammatory cytokine expression levels and the corresponding clinical hormones were analyzed. The changes in the expression (mRNA and protein) levels of the serum inflammatory cytokines were studied by real-time quantitative PCR and protein printing. Fluorescence microscope and flow cytometry were used to detect the glucose uptake capacity of ovarian granulosa cells in PCOS patients under the action of insulin after berberine. RESULTS: In the PCOS group, IL-17a (P = 0.001), IL-1Ra (P<0.0001), and IL-6 (P = 0.035) were significantly higher than those in the non-PCOS group. In the non-PCOS group, AMH level was negatively correlated with inflammatory cytokines IL-17a (r = -0.819;P = 0.004), IL-1a (r = -0.716;P = 0.0.02), IL-1b (r = -0.678;P = 0.031), IL-2 (r = -0.765;P = 0.01), and IL-8 (r = -0.705;P = 0.023). However, in the PCOS group, AMH levels were not significantly correlated with the levels of the examined inflammatory cytokines. Berberine significantly reduced the expression level of mTOR mRNA (P = 0.001), and increased the expression level of IRS-1 mRNA (P = 0.009) in the PCOS granule cells. CONCLUSION: In this study, we find that the elevated levels of serum inflammatory factors IL-17a, IL-1Ra, and IL-6 cause women to be in a subclinical inflammatory state for a long time. Abnormal changes in inflammatory factors alter their original negative correlations with AMH levels, thereby weakening the metabolism of glycolipids, promoting insulin resistance, destroying the normal ovulation and fertilization system of women, leading to polycystic ovary syndrome characterized by menstrual thinning and abnormal ovulation. Berberine can improve the sensitivity of insulin by regulating the signal pathway of insulin receptor substrate-1 (IRS-1) and mammalian target of rapamycin (mTOR) in PCOS patients and achieve a therapeutic effect of treating PCOS.


Assuntos
Anti-Inflamatórios/uso terapêutico , Berberina/uso terapêutico , Insulina/sangue , Interleucinas/sangue , Síndrome do Ovário Policístico/metabolismo , Adulto , Anti-Inflamatórios/administração & dosagem , Hormônio Antimülleriano/metabolismo , Berberina/administração & dosagem , Células Cultivadas , Feminino , Glicolipídeos/metabolismo , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Proteínas Substratos do Receptor de Insulina/metabolismo , Resistência à Insulina , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/tratamento farmacológico , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo
7.
Int J Nanomedicine ; 15: 4191-4203, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32606672

RESUMO

Purpose: To characterize the nanoparticle of antroquinonol from A. cinnamomea and its ameliorative effects on the reproductive dysfunction in the diabetic male rat. Material and Methods: The chitosan-silicate nanoparticle was used as the carrier for the delivery of antroquinonol from solid-state-cultured A. cinnamomea extract (AC). The rats were fed with a high-fat diet and intraperitoneally injected with streptozotocin to induce diabetes. The rats were daily oral gavage by water [Diabetes (DM) and Control groups], three different doses of chitosan-silicate nanoparticle of antroquinonol from solid-state-cultured A. cinnamomea (nano-SAC, NAC): (DM+NAC1x, 4 mg/kg of body weight; DM+NAC2x, 8 mg/kg; and DM+NAC5x, 20 mg/kg), solid-state-cultured AC (DM+AC5x, 20 mg/kg), or metformin (DM+Met, 200 mg/kg) for 7 weeks. Results: The nano-SAC size was 37.68±5.91 nm, the zeta potential was 4.13±0.49 mV, encapsulation efficiency was 79.29±0.77%, and loading capacity was 32.45±0.02%. The nano-SAC can improve diabetes-induced reproductive dysfunction by regulating glucose, insulin, and oxidative enzyme and by increasing the level of testosterone, follicle-stimulating hormone, luteinizing hormone, and sperm count as well as sperm mobility. In testicular histopathology, the seminiferous tubules of A. cinnamomea-supplemented diabetic rats showed similar morphology with the control group. Conclusion: The nanoparticle of antroquinonol from Antrodia cinnamomea can be used as an effective strategy to improve diabetes-induced testicular dysfunction.


Assuntos
Antrodia/química , Diabetes Mellitus Experimental/tratamento farmacológico , Nanopartículas/química , Reprodução , Ubiquinona/análogos & derivados , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Jejum/sangue , Glutationa Peroxidase/metabolismo , Humanos , Insulina/efeitos adversos , Insulina/sangue , Rim/efeitos dos fármacos , Rim/fisiopatologia , Fígado/efeitos dos fármacos , Fígado/fisiopatologia , Masculino , Malondialdeído/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Contagem de Espermatozoides , Motilidade Espermática/efeitos dos fármacos , Estreptozocina , Superóxido Dismutase/metabolismo , Testículo/efeitos dos fármacos , Testículo/patologia , Ubiquinona/farmacologia , Ubiquinona/uso terapêutico
8.
Nature ; 583(7817): 620-624, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32669709

RESUMO

Approximately 75% of all breast cancers express the oestrogen and/or progesterone receptors. Endocrine therapy is usually effective in these hormone-receptor-positive tumours, but primary and acquired resistance limits its long-term benefit1,2. Here we show that in mouse models of hormone-receptor-positive breast cancer, periodic fasting or a fasting-mimicking diet3-5 enhances the activity of the endocrine therapeutics tamoxifen and fulvestrant by lowering circulating IGF1, insulin and leptin and by inhibiting AKT-mTOR signalling via upregulation of EGR1 and PTEN. When fulvestrant is combined with palbociclib (a cyclin-dependent kinase 4/6 inhibitor), adding periodic cycles of a fasting-mimicking diet promotes long-lasting tumour regression and reverts acquired resistance to drug treatment. Moreover, both fasting and a fasting-mimicking diet prevent tamoxifen-induced endometrial hyperplasia. In patients with hormone-receptor-positive breast cancer receiving oestrogen therapy, cycles of a fasting-mimicking diet cause metabolic changes analogous to those observed in mice, including reduced levels of insulin, leptin and IGF1, with the last two remaining low for extended periods. In mice, these long-lasting effects are associated with long-term anti-cancer activity. These results support further clinical studies of a fasting-mimicking diet as an adjuvant to oestrogen therapy in hormone-receptor-positive breast cancer.


Assuntos
Neoplasias da Mama/dietoterapia , Neoplasias da Mama/tratamento farmacológico , Dietoterapia/métodos , Jejum/fisiologia , Fulvestranto/uso terapêutico , Animais , Fatores Biológicos/sangue , Neoplasias da Mama/patologia , Dieta Saudável/métodos , Modelos Animais de Doenças , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Feminino , Fulvestranto/administração & dosagem , Humanos , Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Leptina/sangue , Células MCF-7 , Camundongos Endogâmicos NOD , Camundongos SCID , PTEN Fosfo-Hidrolase/metabolismo , Piperazinas/administração & dosagem , Piperazinas/uso terapêutico , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Receptores Estrogênicos , Receptores de Progesterona , Tamoxifeno/efeitos adversos , Tamoxifeno/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
9.
Am J Physiol Regul Integr Comp Physiol ; 319(2): R211-R222, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32609532

RESUMO

Although severe intermittent hypoxia (IH) is well known to induce deleterious cardiometabolic consequences, moderate IH may induce positive effects in obese individuals. The present study aimed to evaluate the effect of two hypoxic conditioning programs on cardiovascular and metabolic health status of overweight or obese individuals. In this randomized single-blind controlled study, 35 subjects (54 ± 9.3 yr, 31.7 ± 3.5 kg/m2) were randomized into three 8-wk interventions (three 1-h sessions per week): sustained hypoxia (SH), arterial oxygen saturation ([Formula: see text]) = 75%; IH, 5 min [Formula: see text] = 75% - 3 min normoxia; normoxia. Ventilation, heart rate, blood pressure, and tissue oxygenation were measured during the first and last hypoxic conditioning sessions. Vascular function, blood glucose and insulin, lipid profile, nitric oxide metabolites, and oxidative stress were evaluated before and after the interventions. Both SH and IH increased ventilation in hypoxia (+1.8 ± 2.1 and +2.3 ± 3.6 L/min, respectively; P < 0.05) and reduced normoxic diastolic blood pressure (-12 ± 15 and -13 ± 10 mmHg, respectively; P < 0.05), whereas changes in normoxic systolic blood pressure were not significant (+3 ± 9 and -6 ± 13 mmHg, respectively; P > 0.05). IH only reduced heart rate variability (e.g., root-mean-square difference of successive normal R-R intervals in normoxia -21 ± 35%; P < 0.05). Both SH and IH induced no significant change in body mass index, vascular function, blood glucose, insulin and lipid profile, nitric oxide metabolites, or oxidative stress, except for an increase in superoxide dismutase activity following SH. This study indicates that passive hypoxic conditioning in obese individuals induces some positive cardiovascular and respiratory improvements despite no change in anthropometric data and even a reduction in heart rate variability during IH exposure.


Assuntos
Glicemia/metabolismo , Pressão Sanguínea/fisiologia , Sistema Cardiovascular/fisiopatologia , Frequência Cardíaca/fisiologia , Hipóxia/fisiopatologia , Obesidade/fisiopatologia , Sobrepeso/fisiopatologia , Adulto , Sistema Cardiovascular/metabolismo , Colesterol/sangue , Feminino , Humanos , Hipóxia/metabolismo , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Sobrepeso/metabolismo , Método Simples-Cego , Triglicerídeos/sangue
10.
Chem Biol Interact ; 328: 109197, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32710900

RESUMO

The present study was undertaken to assess the effect of imatinib mesylate; a tyrosine kinase inhibitor and a well-known anticancer with numerous medical benefits on blood sugar levels, insulin, and glucagon secretion in an experimental model of STZ-induced diabetes mellitus. Type 1 diabetes mellitus (T1DM) was induced by a single I.P. injection of Streptozotocin (STZ) (50 mg/kg) in male Sprague-Dawley rats. Daily oral imatinib (10 mg/kg) and (20 mg/kg) for 4 weeks induced a significant attenuation in signs of DM in rats reflected in their assessed lab values. Biomarkers of cell injury, tissue necrosis, and apoptosis; caspase-3 were significantly reduced with imatinib treatment. Furthermore, pancreatic antioxidants defenses of which; superoxide dismutase (SOD) and catalase activities, reduced glutathione (GSH) concentration, and total antioxidant capacity have significantly improved with a simultaneous reduction in malondialdehyde (MDA) content. Histopathologically, imatinib treatment was associated with a minimal pancreatic injury and marked restoration of insulin content in ß-cells. Moreover, imatinib treatment revealed a significant reduction in the infiltration of macrophages in ß-cells. Imatinib's ameliorative impact on DM may be attributed to it's mediated protection and preservation of pancreatic ß-cells function and the improvement in serum insulin levels and hence the improvement of blood glucose and overall glycemic control.


Assuntos
Diabetes Mellitus Experimental/patologia , Mesilato de Imatinib/farmacologia , Células Secretoras de Insulina/metabolismo , Administração Oral , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Antioxidantes/metabolismo , Biomarcadores/sangue , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Caspase 3/metabolismo , Catalase/metabolismo , Diabetes Mellitus Experimental/sangue , Modelos Animais de Doenças , Glucagon/sangue , Glutationa/metabolismo , Insulina/sangue , Células Secretoras de Insulina/efeitos dos fármacos , Masculino , Malondialdeído/metabolismo , Tamanho do Órgão/efeitos dos fármacos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Estreptozocina , Superóxido Dismutase/metabolismo
11.
PLoS One ; 15(6): e0235049, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32603369

RESUMO

BACKGROUND: Short sleep duration has been suggested to lead to insulin resistance both directly by altering glucose metabolism and indirectly through obesity. This study aims to investigate associations between nocturnal sleep duration and insulin resistance considering abdominal obesity as a mediator. METHODS: We analysed data of 3 900 children aged 2-15 years participating in the second (2009/10) and third (2013/14) examination wave of the European IDEFICS/I.Family study (hereafter referred to as baseline and follow-up). Information on nocturnal sleep duration was collected by questionnaires and age-standardised (SLEEP z-score). The homeostasis model assessment (HOMA) was calculated from fasting insulin and fasting glucose obtained from blood samples; waist circumference (WAIST) was measured with an inelastic tape. HOMA and WAIST were used as indicators for insulin resistance and abdominal obesity, respectively, and transformed to age- and sex-specific z-scores. Cross-sectional and longitudinal associations between SLEEP z-score and HOMA z-score were investigated based on a path model considering WAIST z-score as a mediator adjusting for relevant confounders. RESULTS: Cross-sectionally, baseline SLEEP z-score was negatively associated with baseline WAIST z-score (unstandardised effect estimate -0.120, 95% confidence interval [-0.167; -0.073]). We observed no direct effect of baseline SLEEP z-score on baseline HOMA z-score but a negative indirect effect through baseline WAIST z-score (-0.042 [-0.058; -0.025]). Longitudinally, there was no direct effect of baseline SLEEP z-score on HOMA z-score at follow-up but a negative indirect effect through both baseline WAIST z-score and WAIST z-score at follow-up (-0.028 [-0.040; -0.016]). CONCLUSIONS: Our results do not support the hypothesis of an association between short sleep duration and insulin resistance independent of abdominal obesity. However, longer sleep duration may exert short and long term beneficial effects on insulin resistance through its beneficial effects on abdominal obesity.


Assuntos
Resistência à Insulina , Obesidade Abdominal/epidemiologia , Sono , Adolescente , Glicemia/análise , Criança , Pré-Escolar , Estudos Transversais , Europa (Continente) , Feminino , Humanos , Insulina/sangue , Estudos Longitudinais , Masculino , Circunferência da Cintura
12.
Life Sci ; 257: 118118, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32702445

RESUMO

AIMS: Recent findings have instituted the role of hyperglycemia-related AGE/RAGE and NF-κB in instigating reactive oxygen species (ROS) mediated mitochondrial dysfunction and apoptosis of hepatocyte, which leads to steatohepatitis. Naringin, a flavanone glycoside found to possess myriads of pharmacological benefits along with its antioxidant and anti-inflammatory properties. Consequently, we aimed to decipher the effect of naringin on RAGE/NF-κB mediated mitochondrial apoptosis in type 2 diabetes mellitus (T2DM)-induced steatohepatitis. MAIN METHODS: Hepatic HepG2 cells were cultured in palmitic acid medium with and without naringin. Lipid content was examined by Oil Red O and Nile Red staining. Cellular apoptosis was determined by Annexin V-FITC/PI staining. An experimental T2DM-induced steatohepatitis was developed in Sprague Dawley rats by high-fat diet (HFD) for 12 weeks. The naringin was administrated orally at a dose of 100 mg/kg, daily for eight weeks. Glucose and insulin tolerance test was performed. Liver sections were stained by hematoxylin-eosin and picrosirius red. The mRNA and protein expression of RAGE and NF-κB were determined by qPCR, Immunofluorescence, and Immunoblotting. Mitochondrial membrane potential (MMP), cellular and mitochondrial ROS were measured by FACS. KEY FINDINGS: Palmitic acid encountered HepG2 cells and HFD fed rats exhibited hyperlipidemia, insulin resistance, abnormal aminotransferases, steatosis, and fibrosis. Besides, the level of AGEs, RAGE, NF-κB, and oxidative stress were exacerbated. Moreover, MMP, cellular and mitochondrial ROS were altered in diabetic rats. Nevertheless, the naringin treatment ameliorated the steatohepatitis by improving the levels of aforementioned parameters. SIGNIFICANCE: Collectively, these findings suggested anti-steatohepatitis potential of naringin in diabetics.


Assuntos
Antioxidantes/uso terapêutico , Apoptose/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Fígado Gorduroso/tratamento farmacológico , Flavanonas/uso terapêutico , Mitocôndrias/efeitos dos fármacos , NF-kappa B/metabolismo , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Animais , Diabetes Mellitus Experimental/complicações , Fígado Gorduroso/etiologia , Fígado Gorduroso/patologia , Imunofluorescência , Teste de Tolerância a Glucose , Células Hep G2/efeitos dos fármacos , Humanos , Insulina/sangue , Fígado/patologia , Masculino , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Reação em Cadeia da Polimerase em Tempo Real
13.
Am J Physiol Regul Integr Comp Physiol ; 319(3): R255-R263, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32667834

RESUMO

Fetal conditions associated with placental insufficiency and intrauterine growth restriction (IUGR) chronically elevate plasma norepinephrine (NE) concentrations. Our objective was to evaluate the effects of chronically elevated NE on insulin-stimulated glucose metabolism in normally grown, non-IUGR fetal sheep, which are independent of other IUGR-related reductions in nutrients and oxygen availability. After surgical placement of catheters, near-term fetuses received either a saline (control) or NE intravenous infusion with controlled euglycemia. In NE fetuses, plasma NE concentrations were 5.5-fold greater than controls, and fetal euglycemia was maintained with a maternal insulin infusion. Insulin secretion was blunted in NE fetuses during an intravenous glucose tolerance test. Weight-specific fluxes for glucose were measured during a euinsulinemic-euglycemic clamp (EEC) and a hyperinsulinemic-euglycemic clamp (HEC). Plasma glucose and insulin concentrations were not different between groups within each clamp, but insulin concentrations increased 10-fold between the EEC and the HEC. During the EEC, rates of glucose uptake (umbilical uptake + exogenous infusion) and glucose utilization were 47% and 35% lower (P < 0.05) in NE fetuses compared with controls. During the HEC, rates of glucose uptake were 28% lower (P < 0.05) in NE fetuses than controls. Glucose production was undetectable in either group, and glucose oxidation was unaffected by the NE infusion. These findings indicate that chronic exposure to high plasma NE concentrations lowers rates of net glucose uptake in the fetus without affecting glucose oxidation rates or initiating endogenous glucose production. Lower fetal glucose uptake was independent of insulin, which indicates insulin resistance as a consequence of chronically elevated NE.


Assuntos
Glicemia/metabolismo , Feto/metabolismo , Norepinefrina/sangue , Insuficiência Placentária/metabolismo , Animais , Feminino , Retardo do Crescimento Fetal/metabolismo , Insulina/sangue , Resistência à Insulina/fisiologia , Ilhotas Pancreáticas/metabolismo , Gravidez , Ovinos
14.
Phys Rev Lett ; 124(20): 208101, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32501061

RESUMO

Network flows often exhibit a hierarchical treelike structure that can be attributed to the minimization of dissipation. The common feature of such systems is a single source and multiple sinks (or vice versa). In contrast, here we study networks with only a single source and sink. These systems can arise from secondary purposes of the networks, such as blood sugar regulation through insulin production. Minimization of dissipation in these systems leads to vascular shunting, a single vessel connecting the inlet and outlet. We show instead how optimizing the transport time yields network topologies that match those observed in the insulin-producing pancreatic islets. These are patterns of periphery-to-center and center-to-periphery flows. The obtained flow networks are broadly independent of how the flow velocity depends on the flow flux, but continuous and discontinuous phase transitions appear at extreme flux dependencies. Lastly, we show how constraints on flows can lead to buckling of the branches of the network, a feature that is also observed in pancreatic islets.


Assuntos
Ilhotas Pancreáticas/irrigação sanguínea , Ilhotas Pancreáticas/metabolismo , Modelos Cardiovasculares , Transporte Biológico , Glucagon/sangue , Glucagon/metabolismo , Insulina/sangue , Insulina/metabolismo , Transdução de Sinais
15.
Orv Hetil ; 161(26): 1088-1093, 2020 06.
Artigo em Húngaro | MEDLINE | ID: mdl-32541087

RESUMO

Confirming or ruling out the presence of insulin resistance (IR) is one of the most common reasons for referral to non-diabetics in Hungary for diabetes outpatient units. The article overviews the concept of IR, its importance in pathophysiology, the diagnostic capabilities, and its treatment implications. It emphasizes that the decline in insulin activity is a co-morbidity of many diseases and does not, in itself, require detailed examination without other symptoms. If this occurs, it is sufficient to calculate the HOMA-IR value and determine fasting blood glucose and serum insulin levels for information purposes. If it is confirmed as part of a comorbid condition, complex treatment is required. Orv Hetil. 2020; 161(26): 1088-1093.


Assuntos
Glicemia/metabolismo , Jejum/sangue , Resistência à Insulina , Insulina/sangue , Diabetes Mellitus/sangue , Diabetes Mellitus Tipo 2 , Humanos , Hungria
16.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(1): 12-16, 2020 Jan 28.
Artigo em Chinês | MEDLINE | ID: mdl-32476367

RESUMO

OBJECTIVE: To study the effects of acute and chronic exercise on phosphatidylinositol 3-hydroxy kinase(PI3K)/protein kinase B(AKT)/glucose transporter 4(GLUT4)signaling pathway in adipose tissue of rats with type 2 diabetes mellitus (T2DM) induced by high-fat diet and low-dose streptozotocin (STZ). METHODS: A total of 52 SD male rats aged 15 months were randomly divided into normal control group (13) and high-fat group (39), and fed normal and high fat diets. After 8 weeks, the body weight of the high-fat group was higher 20% than that of the normal control group. After a small dose of STZ, the blood glucose level was >16.7 mmol/l, and the model was successfully established. The diabetic model group was randomly divided into a diabetic control group (DC, n=13), a diabetic chronic exercise group (DCE, n=13), and a diabetic acute exercise group (DAE, n=13). The DCE group underwent an 8-week swimming exercise and the DAE group performed a one-time swimming exercise. Blood lipids, blood glucose and serum insulin levels were measured, and the contents of fat PI3K, AKT and GLUT4 proteins were determined by Western blot method. RESULTS: The levels of body weight, blood lipids, blood glucose and insulin in the diabetic group were significantly higher than those in the normal control group (P<0.01); high density liptein cholesterol(HDL-C) levels were decreased (P<0.05), and the expressions of PI3K, AKT and GLUT4 protein in adipose tissue were decreased (P<0.01). After 8 weeks of swimming training, the levels of body weight, blood lipids, blood glucose and insulin all were decreased significantly (P<0.01); while the level of HDL-C was increased (P<0.05), and the expressions of PI3K, AKT and GLUT4 protein were increased (P<0.01). After acute exercise, the levels of blood lipids, blood glucose and insulin were decreased (P<0.05); the level of HDL-C was increased (P<0.05), and the expression levels of fat PI3K, AKT and GLUT4 were increased significantly (P<0.05). CONCLUSION: ①High fat diet combined with low-dose STZ induced damage to the PI3K/AKT pathway in adipose tissue of T2DM rats reduced insulin sensitivity. ②Acute and chronic aerobic exercise can improve the disorder of glucose and lipid metabolism through PI3K/AKT pathway, and the chronic exercise is better than acute exercise.


Assuntos
Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 2/terapia , Resistência à Insulina , Condicionamento Físico Animal , Transdução de Sinais , Animais , Glicemia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Insulina/sangue , Lipídeos/sangue , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley
17.
PLoS One ; 15(6): e0232749, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574162

RESUMO

BACKGROUND: Maternal obesity is increasing worldwide but the consequences for maternal physiology and fetal growth are not fully understood. OBJECTIVE: To study whether changes in glucose and lipid metabolism during pregnancy differ between women with normal weight and overweight/obesity, and investigate which of these metabolic factors are associated with birthweight. DESIGN: Prospective, longitudinal study. SETTING: Department of Obstetrics, Oslo University Hospital, Rikshospitalet. POPULATION: 1031 healthy pregnant women with singleton pregnancies. METHODS: Blood samples from early and late pregnancy were analyzed for fasting glucose, insulin and lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Associations between metabolic factors and birthweight (z-scores) were explored by linear regression models. Main Outcome Measures: Group-dependent longitudinal changes in glucose and lipids and their association with birthweight (z-scores). RESULTS: Compared to women with normal weight (BMI < 25), women with overweight (BMI 25-29.9) and obesity (BMI > 30) had significantly higher fasting glucose (4.54, 4.68 and 4.84 mmol/l), insulin (23, 33 and 50 pmol/l), total cholesterol (4.85, 4.99 and 5.14 mmol/l), LDL-C (2.49, 2.66 and 2.88 mmol/l) and triglycerides (1.10, 1.28 and 1.57 mmol/l), but lower HDL-C (1.86, 1.75 and 1.55 mmol/l). BMI (B 0.05, 95% CI 0.03-0.06, p<0.001), gestational weight gain (GWG) (B 0.06, 0.05-0.08, p<0.001) and an increase in fasting glucose (B 0.30, 0.16-0.43, p<0.001) were positively associated with birthweight, whereas a decrease in HDL-C (B -0.72, -0.96- -0.53, p<0.001) had a negative association with birthweight. CONCLUSIONS: Overweight/obesity was associated with an unfavorable metabolic profile in early pregnancy which was associated with increased birthweight. However, modifiable factors like gestational weight gain and an increase in fasting glucose were identified and can be targeted for interventions.


Assuntos
Peso ao Nascer , Glicemia , Índice de Massa Corporal , Lipídeos/sangue , Obesidade/epidemiologia , Complicações na Gravidez/epidemiologia , Adulto , Feminino , Ganho de Peso na Gestação , Humanos , Insulina/sangue , Estudos Longitudinais , Obesidade/sangue , Gravidez , Complicações na Gravidez/sangue , Estudos Prospectivos
18.
Int J Sports Med ; 41(11): 751-758, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32485778

RESUMO

We investigated early effects of Whole-Body Electromyostimulation added to hypocaloric diet on metabolic syndrome features in sedentary middle-aged individuals. We randomly assigned 25 patients to Whole-Body Electromyostimulation plus caloric restriction or caloric restriction alone for 26 weeks. Anthropometrics, blood pressure, fasting glucose and insulin, HOMA-IR, glycated hemoglobin, lipids, uric acid, creatinphosphokynase, C-reactive protein were assessed. Body composition was evaluated with direct-segmental, multi-frequency Bioelectrical Impedance Analysis. Both groups lost approximately 10% of weight, with similar effects on waist circumference and fat mass. Change in free-fat mass was significantly different between groups (caloric restriction -1.5±0.2 vs. Whole-Body Electromyostimulation plus caloric restriction +1.1±0.4 kg, p=0.03). Whole-Body Electromyostimulation plus caloric restriction group experienced greater percent reductions in insulin (-45.5±4.4 vs. -28.2±3.6%, p=0.002), HOMA-IR (-51.3±3.2 vs. -25.1±1.8%, p=0.001), triglycerides (-22.5±2.9 vs. -4.1±1.6%, p=0.004) and triglycerides/HDL (p=0.028). Subjects trained with Whole-Body Electromyostimulation had also significant improvement in systolic pressure (138±4 vs. 126±7 mmHg, p=0.038). No discontinuations for adverse events occurred. In middle-aged sedentary subjects with the metabolic syndrome, Whole-Body Electromyostimulation with caloric restriction for 26 weeks can improve insulin-resistance and lipid profile compared to diet alone. Further studies are needed to ascertain long-term efficacy and feasibility of this approach in individuals with the metabolic syndrome.


Assuntos
Restrição Calórica , Terapia por Estimulação Elétrica/métodos , Síndrome Metabólica/terapia , Antropometria , Biomarcadores/sangue , Glicemia/metabolismo , Colesterol/sangue , HDL-Colesterol/sangue , Creatina Quinase/sangue , Dieta Redutora , Terapia por Estimulação Elétrica/efeitos adversos , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/dietoterapia , Pessoa de Meia-Idade , Músculo Esquelético/enzimologia , Músculo Esquelético/lesões , Estudo de Prova de Conceito , Triglicerídeos/sangue , Perda de Peso
19.
Chemosphere ; 258: 126940, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32540546

RESUMO

Exposures to heavy metals play a role in the etiopathogenesis of diabetes. Epidemiological studies investigating a potential sex-specific linkage between manganese (Mn) exposures and glucose homeostasis are rare. We comprehensively estimated the associations of blood and urinary Mn levels with fasting plasma glucose (FPG), hemoglobin A1c (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), insulin, and estimated glomerular filtration rate (eGFR) among 1417 adults in the US National Health and Nutrition Examination Survey (NHANES) 2011-2016. We further examined the potential heterogeneities by sex and joint-effects of multiple metal exposures by the Bayesian kernel machine regression (BKMR). Among women, we found positive linear relationships between urinary Mn with FPG (Poverall = 0.003, Pnonlinear = 0.817) and HbA1c (Poverall = 0.023, Pnonlinear = 0.854). Among men, J-shaped relationships were observed between blood Mn with HOMA-IR (Pnonlinear = 0.042) and insulin (Pnonlinear = 0.014). For eGFR, positive linear relationships were obserned among women for blood Mn (Pnonlinear = 0.549) and among both men and women for urinary Mn levels. The joint-effects of urinary Mn with molybdenum (Mo) on FPG and HbA1c, urinary Mn with cadmium (Cd) and cesium (Cs) on eGFR, and blood Mn with Cd and lead (Pb) on eGFR were detected. In summary, blood and urinary Mn levels were independently associated with glucose levels, insulin resistance and kidney function with potential sex-dependent heterogeneities. These findings emphasize the probable role of Mn in the regulation of glucose metabolism and kidney function, and confirm the need for more studies on sex-specific risk of diabetes.


Assuntos
Glicemia/análise , Taxa de Filtração Glomerular , Resistência à Insulina , Manganês/sangue , Manganês/urina , Adolescente , Adulto , Idoso , Teorema de Bayes , Glicemia/metabolismo , Cádmio/urina , Estudos Transversais , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Insulina/sangue , Resistência à Insulina/fisiologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Fatores Sexuais , Estados Unidos , Adulto Jovem
20.
PLoS One ; 15(6): e0234319, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32542057

RESUMO

AIMS: Robust evidence supports intensive glucose control in those with recently diagnosed type 1 diabetes to reduce the risk of developing micro- and macrovascular complications. Data to support longitudinal glycaemic targets is lacking. We aimed to explore if longer duration of diabetes and greater age might reduce the impact of glycaemia on the risk of vascular complications. RESEARCH AND DESIGN METHODS: Data for adults age 20 years or more, was extracted from a clinical database of people with type 1 diabetes cared for at a London teaching hospital. The presence or absence of micro- and macro-vascular complications was recorded. Multivariable logistic regression analysis was performed using HbA1c as independent variable, diabetes duration and age as continuous variable and obesity, hypertension, hypercholesterolaemia, low HDL cholesterol and hypertriglyceridaemia as categorical variables. RESULTS: Data from 495 patients was used. HbA1c above 60 mmol/mol (7.6%) was associated with increased microvascular complications in patients aged 20-44 years, independent of age and duration of diabetes. In older people with T1DM duration of diabetes was the major risk factor. CONCLUSIONS: Our study suggests that increased age and greater duration of diabetes reduce the impact of glycaemia on the risk of vascular complications. Intensive blood glucose management in patients aged ≥45 years may have limited benefits in terms of reducing the risk of complications although this does not dismiss the benefits of good glycaemic control in older people with T1DM.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Angiopatias Diabéticas/sangue , Hemoglobina A Glicada/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/prevenção & controle , Feminino , Carga Glicêmica , Humanos , Hipoglicemiantes , Insulina/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Fatores de Risco , Adulto Jovem
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