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1.
Front Endocrinol (Lausanne) ; 14: 1191090, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37424876

RESUMO

Background: The triglyceride glucose index (TyG index) has been regarded as a reliable surrogate marker of insulin resistance and an independent predictor of diabetes. However, few studies have reported the association between the TyG index and diabetes in the elderly population. Accordingly, this study aimed to investigate the association between the TyG index and diabetes progression in elderly Chinese. Methods: Baseline medical history, fasting plasma glucose (FPG), glucose levels during the oral glucose tolerance test (OGTT) after 1-hour (1h-PG) and 2-hour (2h-PG), and triglyceride (TG) were obtained from a cohort of 862 elderly (aged ≥ 60 years) Chinese in the Beijing urban area between 1998 and 1999. A follow-up visit was conducted between 1998 and 2019 to assess incident diabetes. TyG index was calculated by the following formula ln[TG (mg/dL) × FPG (mg(dL)/2]. The predictive values of TyG index, lipids, and glucose levels during OGTT were assessed alone and also in a clinical prediction model comprising traditional risk factors using concordance index (C-index). Areas under the receiver operating characteristics curves (AUC) and 95% CIs were calculated. Results: After 20 years of follow-up, there were 544 cases of incident type 2 diabetes mellitus (63.1% of incidence). The multivariable HRs (95% CI) for TyG index, FPG, 1h-PG and 2h-PG, high-density lipoprotein-cholesterol (HDL-c), and TG were 1.525 (1.290-1.804), 1.350 (1.181-1.544), 1.337 (1.282-1.395), 1.401 (1.327-1.480), 0.505 (0.375-0.681), and 1.120 (1.053-1.192), respectively. The corresponding C-index were 0.623, 0.617, 0.704, 0.694, 0.631, and 0.610, respectively. The AUC (95% CI) for the TyG index, FPG, 1h-PG, 2h-PG, HDL-c, and TG were 0.608 (0.569-0.647), 0.587 (0.548-0.625), 0.766 (0.734-0.797), 0.713 (0.679-0.747), 0.397 (0.358-0.435), and 0.588 (0.549-0.628). The AUC of the TyG index was higher than that of TG but did not differ with FPG and HDL-c. In addition, the AUCs of 1h-PG and 2h-PG were higher than that of the TyG index. Conclusions: Elevated TyG index is independently correlated with an increased risk of incident diabetes in the elderly male population, but it is not superior to OGTT 1h-PG and 2h-PG in predicting the risk of diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Glucose , Humanos , Masculino , Idoso , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Estudos Retrospectivos , Triglicerídeos , Incidência , População do Leste Asiático , Modelos Estatísticos , Glicemia , Prognóstico , HDL-Colesterol
2.
Bioengineered ; 12(1): 4887-4898, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34369277

RESUMO

Formononetin (FMNT), a flavonoid identified from the Chinese herb Astragalus membranaceus, possesses anti-inflammatory or anti-oxidative properties in different human diseases. This study aims to comprehensively elucidate the function of FMNT in atherosclerosis and its underlying mechanisms. Online public databases were used to identify the drug-disease targets. Protein-protein interaction (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were applied to explore the potential targets and signaling pathways involved in FMNT against atherosclerosis. Human umbilical vein endothelial cells (HUVECs) were exposed to oxidized low-density lipoprotein (ox-LDL) to construct an atherosclerosis cell model in vitro. Endothelial cell function was assessed via examining cell proliferation, inflammatory factors, oxidative markers, reactive oxygen species (ROS), and apoptosis. Western blot was performed to detect the expression of cyclooxygenase-2 (COX-2), endothelial nitric oxide synthase (eNOS), cleaved caspase-3, and peroxisome proliferator-activated receptor-γ (PPAR-γ). A total of 39 overlapping target genes of FMNT and atherosclerosis were identified. Through the PPI network analysis, 14 hub genes were screened and found to be closely relevant to inflammation, oxidative stress, and apoptosis. Results of KEGG pathway assays indicated that lots of targets were enriched in PPAR signaling. Functionally, FMNT could protect against ox-LDL-induced inflammatory reaction, oxidative stress, and apoptosis in HUVECs. Moreover, FMNT attenuated ox-LDL-mediated inactivation of PPAR-γ signaling. GW9662, a PPAR-γ antagonist, reversed the inhibitory effect of FMNT on ox-LDL-induced endothelial injury. In conclusion, FMNT alleviates ox-LDL-induced endothelial injury in HUVECs by stimulating PPAR-γ signaling, providing a theoretical basis for employing FMNT as a potential drug to combat atherosclerosis.Abbreviations: FMNT: formononetin; PPI: protein-protein interaction; GO: Gene Ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; HUVECs: human umbilical vein endothelial cells; ox-LDL: oxidized low-density lipoprotein; COX-2: cyclooxygenase-2; eNOS: endothelial nitric oxide synthase; PPAR-γ: peroxisome proliferator-activated receptor-γ; CVD: cardiovascular disease; TCM: traditional Chinese medicines; OGDR: oxygen-glucose deprivation/reoxygenation; ROS: reactive oxygen species; FBS: fetal bovine serum; CCK-8: cell counting kit-8; EdU: 5-Ethynyl-2'-deoxyuridine; SOD: antioxidant enzymes superoxide dismutase; MDA: malondialdehyde; DCFH-DA: 2',7'-dichlorofluorescein-diacetate; PVDF: polyvinylidene fluoride; ANOVA: one-way analysis of variance; PPARs: peroxisome proliferation-activated receptors.


Assuntos
Antioxidantes/farmacologia , Isoflavonas/farmacologia , Lipoproteínas LDL/metabolismo , PPAR gama/metabolismo , Apoptose/efeitos dos fármacos , Aterosclerose/metabolismo , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação/metabolismo , Farmacologia em Rede , Estresse Oxidativo/efeitos dos fármacos , Mapas de Interação de Proteínas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
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