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1.
Kardiologiia ; 64(1): 67-79, 2024 Jan 31.
Artigo em Russo, Inglês | MEDLINE | ID: mdl-38323447

RESUMO

AIM: To develop prognostic models for arterial hypertension (AH) and atherosclerosis based on studying the totality and significance of traditional and disease-mediated risk factors (RFs) in women with rheumatoid arthritis (RA). MATERIAL AND METHODS: 223 female patients with RA aged 54.9±2.1 years were evaluated at the premises of the polyclinic of the Gulla Municipal Hospital #4 (Barnaul), the "Health Center", the City Rheumatology Department of the polyclinic, and the Hospital Department in 2016-2019. Statistical analysis was performed using Excel Microsoft Office 2007, Statistica 6.0 and 10.0, and SigmaPlot 12.5 software packages. Multivariate regression analysis was used for studying the attributes influencing the development of AH and atherosclerosis in RA and for constructing predictive models. ROC analysis was used to determine the quality of the developed models. Differences were considered statistically significant at p<0.05. RESULTS: The following RFs predominating in the onset of disease were identified: traditional (hyperglycemia, obesity, increased diastolic BP (DBP), tachycardia, dyslipidemia); disease-mediated (ESR, fibrinogen, C-reactive protein (CRP), rheumatoid factor, cyclic citrullinated peptide antibodies, moderate and high DAS-28 activity), and psychosocial (stress, anxiety, depression, sleep disorders). The highest RF incidence and their combinations were determined with a RA duration of more than a year: traditional (obesity, hyperglycemia, increased systolic BP (SBP)), and decreased glomerular filtration rate; and disease-mediated (prednisolone treatment). A highly sensitive model for AH screening was developed that included a combination of RFs: disease-mediated (RA duration, CRP); traditional (improper diet, low physical activity, history of early cardiovascular diseases, increased SBP and DBP, preeclampsia and/or eclampsia, early menopause, older age, dyslipidemia); psychosocial (anxiety, depression), and a high salt-taste threshold. A highly sensitive model was developed for probable prediction of multifocal atherosclerosis in RA in women. The model includes a complex of risk factors: disease-mediated (RA activity by DAS-28, CRP, fibrinogen, ESR, dose-dependent prednisolone treatment); traditional (AH, SBP, waist circumference, heart rate, early menopause, preeclampsia and/or eclampsia, age 55 years and older, dyslipidemia); and psychosocial (sleep disorders, depression). CONCLUSION: Algorithms for early prevention of AH and atherosclerosis were developed with consideration of identified predictors and proposed prediction models for women with RA.


Assuntos
Artrite Reumatoide , Aterosclerose , Doenças Cardiovasculares , Dislipidemias , Eclampsia , Hiperglicemia , Hipertensão , Pré-Eclâmpsia , Transtornos do Sono-Vigília , Humanos , Feminino , Proteína C-Reativa , Fibrinogênio , Aterosclerose/epidemiologia , Prednisolona , Obesidade
2.
Cardiovasc Res ; 119(18): 2858-2874, 2024 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-38367275

RESUMO

Ischaemic cardiovascular diseases, including peripheral and coronary artery disease, myocardial infarction, and stroke, remain major comorbidities for individuals with type 2 diabetes (T2D) and obesity. During cardiometabolic chronic disease (CMCD), hyperglycaemia and excess adiposity elevate oxidative stress and promote endothelial damage, alongside an imbalance in circulating pro-vascular progenitor cells that mediate vascular repair. Individuals with CMCD demonstrate pro-vascular 'regenerative cell exhaustion' (RCE) characterized by excess pro-inflammatory granulocyte precursor mobilization into the circulation, monocyte polarization towards pro-inflammatory vs. anti-inflammatory phenotype, and decreased pro-vascular progenitor cell content, impairing the capacity for vessel repair. Remarkably, targeted treatment with the sodium-glucose cotransporter-2 inhibitor (SGLT2i) empagliflozin in subjects with T2D and coronary artery disease, and gastric bypass surgery in subjects with severe obesity, has been shown to partially reverse these RCE phenotypes. SGLT2is and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have reshaped the management of individuals with T2D and comorbid obesity. In addition to glucose-lowering action, both drug classes have been shown to induce weight loss and reduce mortality and adverse cardiovascular outcomes in landmark clinical trials. Furthermore, both drug families also act to reduce systemic oxidative stress through altered activity of overlapping oxidase and antioxidant pathways, providing a putative mechanism to augment circulating pro-vascular progenitor cell content. As SGLT2i and GLP-1RA combination therapies are emerging as a novel therapeutic opportunity for individuals with poorly controlled hyperglycaemia, potential additive effects in the reduction of oxidative stress may also enhance vascular repair and further reduce the ischaemic cardiovascular comorbidities associated with T2D and obesity.


Assuntos
Doenças Cardiovasculares , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Hiperglicemia , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Doença da Artéria Coronariana/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Doenças Cardiovasculares/tratamento farmacológico , Doenças Cardiovasculares/complicações , Obesidade/tratamento farmacológico , Obesidade/complicações , Hiperglicemia/complicações , Hiperglicemia/tratamento farmacológico , Glucose , Regeneração
3.
Sci Rep ; 14(1): 2915, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316854

RESUMO

In type 2 diabetes (T2D), the dawn phenomenon is an overnight glucose rise recognized to contribute to overall glycemia and is a potential target for therapeutic intervention. Existing CGM-based approaches do not account for sensor error, which can mask the true extent of the dawn phenomenon. To address this challenge, we developed a probabilistic framework that incorporates sensor error to assign a probability to the occurrence of dawn phenomenon. In contrast, the current approaches label glucose fluctuations as dawn phenomena as a binary yes/no. We compared the proposed probabilistic model with a standard binary model on CGM data from 173 participants (71% female, 87% Hispanic/Latino, 54 ± 12 years, with either a diagnosis of T2D for six months or with an elevated risk of T2D) stratified by HbA1c levels into normal but at risk for T2D, with pre-T2D, or with non-insulin-treated T2D. The probabilistic model revealed a higher dawn phenomenon frequency in T2D [49% (95% CI 37-63%)] compared to pre-T2D [36% (95% CI 31-48%), p = 0.01] and at-risk participants [34% (95% CI 27-39%), p < 0.0001]. While these trends were also found using the binary approach, the probabilistic model identified significantly greater dawn phenomenon frequency than the traditional binary model across all three HbA1c sub-groups (p < 0.0001), indicating its potential to detect the dawn phenomenon earlier across diabetes risk categories.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Estado Pré-Diabético , Humanos , Feminino , Masculino , Diabetes Mellitus Tipo 2/diagnóstico , Glicemia , Automonitorização da Glicemia
4.
JAMA Netw Open ; 7(2): e2354595, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38324312

RESUMO

Importance: Pediatric data on inpatient home insulin pumps are absent in the literature. Understanding safety of home insulin pumps, managed by patients or caregivers, during times of illness will help diabetes technology securely move into pediatric hospitals. Objective: To examine whether insulin can be safely and accurately delivered to hospitalized children through home insulin pumps when managed by patients or caregivers. Design, Setting, and Participants: This single-center, retrospective, observational cohort study included children with insulin-dependent diabetes admitted to a tertiary children's hospital from January 1, 2016, to December 31, 2021. In all these patients, diabetes was the primary or secondary diagnosis on admission. Exposure: Insulin delivery via home insulin pump, hospital insulin pump, or subcutaneous injection. Main Outcomes and Measures: Hyperglycemia (glucose, >250 mg/dL) and hypoglycemia (glucose, <45 mg/dL) rates (quantified as the proportion of total insulin-days), glucose variability, and diabetic ketoacidosis (DKA) recurrences were compared for hospital pumps (manual mode), home pumps (manual mode), and subcutaneous injections using bivariate tests. Results: There were 18 096 insulin-days among 2738 patients aged 0.5 to 25 years (median age, 15.8 years [IQR, 12.3-18.3 years]). Overall, 990 (5.5%) of insulin-days involved hospital insulin pumps, and 775 (4.3%) involved home pumps. A total of 155 insulin-days (15.7%) involving hospital pumps were hyperglycemic, compared with 209 (27.0%) involving home pumps and 7374 (45.2%) involving injections (P < .001). Moderate hypoglycemia days comprised 31 insulin-days (3.1%) involving hospital pumps compared with 35 (4.5%) involving home pumps and 830 (5.1%) involving injections (P = .02). Severe hypoglycemia did not differ significantly according to insulin delivery method. Two patients using injections (0.01%) developed DKA; no patients using hospital or home pumps developed DKA. Conclusions and Relevance: In this cohort study, home insulin pump use was found to be safe in a children's hospital regarding hyperglycemia and hypoglycemia. These data support use of home insulin pumps during pediatric admissions in patients who do not require intensive care and without active DKA.


Assuntos
Diabetes Mellitus Tipo 1 , Cetoacidose Diabética , Hiperglicemia , Hipoglicemia , Humanos , Criança , Adolescente , Criança Hospitalizada , Estudos de Coortes , Estudos Retrospectivos , Insulina Regular Humana , Insulina , Glucose , Hospitais Pediátricos
5.
FASEB J ; 38(3): e23448, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38305779

RESUMO

Diabetes causes a range of complications that can affect multiple organs. Hyperglycemia is an important driver of diabetes-associated complications, mediated by biological processes such as dysfunction of endothelial cells, fibrosis, and alterations in leukocyte number and function. Here, we dissected the transcriptional response of key cell types to hyperglycemia across multiple tissues using single-cell RNA sequencing (scRNA-seq) and identified conserved, as well as organ-specific, changes associated with diabetes complications. By studying an early time point of diabetes, we focus on biological processes involved in the initiation of the disease, before the later organ-specific manifestations had supervened. We used a mouse model of type 1 diabetes and performed scRNA-seq on cells isolated from the heart, kidney, liver, and spleen of streptozotocin-treated and control male mice after 8 weeks and assessed differences in cell abundance, gene expression, pathway activation, and cell signaling across organs and within organs. In response to hyperglycemia, endothelial cells, macrophages, and monocytes displayed organ-specific transcriptional responses, whereas fibroblasts showed similar responses across organs, exhibiting altered metabolic gene expression and increased myeloid-like fibroblasts. Furthermore, we found evidence of endothelial dysfunction in the kidney, and of endothelial-to-mesenchymal transition in streptozotocin-treated mouse organs. In summary, our study represents the first single-cell and multi-organ analysis of early dysfunction in type 1 diabetes-associated hyperglycemia, and our large-scale dataset (comprising 67 611 cells) will serve as a starting point, reference atlas, and resource for further investigating the events leading to early diabetic disease.


Assuntos
Diabetes Mellitus Tipo 1 , Hiperglicemia , Camundongos , Animais , Masculino , Diabetes Mellitus Tipo 1/genética , Células Endoteliais , Estreptozocina/toxicidade , Camundongos Endogâmicos C57BL , Hiperglicemia/genética , Análise de Sequência de RNA
6.
PLoS One ; 19(2): e0297082, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38306369

RESUMO

INTRODUCTION: Diabetic nephropathy (DN) is a long-term kidney disease among diabetic patients. It is the leading cause of end-stage renal failure. In Ethiopia, DN affects the majority of diabetic populations, but there were inconsistent findings about the determinant factors across the studies. METHODS: We have accessed studies using PubMed, Embase, EBSCO, Web of Science, OVID, and search engines including Google and Google Scholar published up to June 2023. The study populations were diabetic patients with nephropathy. The quality of each included article was assessed using the Newcastle-Ottawa quality assessment scale. The odds ratios of risk factors were pooled using a random-effect meta-analysis model. Heterogeneity was assessed using the Cochrane Q statistics and I-Square (I2). The publication bias was detected using the funnel plot and/or Egger's test (p< 0.05). Trim and fill analysis was carried out to treat the publication bias. The protocol has been registered with the reference number CRD42023434547. RESULTS: A total of sixteen articles were used for this reviewed study. Of which, eleven articles were used for advanced age, ten articles for duration of diabetic illness, ten articles for poor glycemic control, and eleven articles for having co-morbid hypertension. Diabetic patients with advanced age (AOR = 1.11, 95% CI: 1.03-120, I2 = 0.0%, p = 0.488), longer duration of diabetic illness (AOR = 1.23, 95% CI = 1.05-1.45, I2 = 0.0%, p = 0.567), poor glycemic control (AOR = 2.57, 95% CI: 1.07-6.14; I2 = 0.0%, p = 0.996), and having co-morbid hypertension (AOR = 4.03, 95% CI: 2.00-8.12, I2 = 0.0%, p = 0.964) were found to be factors associated with DN. CONCLUSIONS: The findings of the study revealed that diabetic patients with advanced age, longer duration of diabetic illness, poor glycemic control status, and co-morbid hypertension were the determinant factors of DN. Therefore, treatment of co-morbid hypertension and high blood glucose and regular screening of renal function should be implemented to detect, treat, and reduce the progression of DN. Furthermore, healthcare workers should give due attention to diabetes with advanced age and a longer duration of diabetes illness to prevent the occurrence of DN.


Assuntos
Diabetes Mellitus , Nefropatias Diabéticas , Hiperglicemia , Hipertensão , Humanos , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/epidemiologia , Etiópia/epidemiologia , Fatores de Risco , Hiperglicemia/complicações , Hipertensão/complicações , Hipertensão/epidemiologia , Prevalência , Diabetes Mellitus/epidemiologia
7.
Diabetes Res Clin Pract ; 208: 111122, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38307141

RESUMO

AIMS: The stress hyperglycemia ratio (SHR) is significantly associated with short-term adverse cardiovascular events. However, the association between SHR and mortality after the acute phase of acute coronary syndrome (ACS) remains controversial. METHODS: This study used data from the Medical Information Mart for Intensive Care-IV database. Patients with ACS hospitalized in the intensive care unit (ICU) were retrospectively enrolled. RESULTS: A total of 2668 ACS patients were enrolled. The incidence of in-hospital and 1-year mortality was 4.7 % and 13.2 %, respectively. The maximum SHR had a higher prognostic value for predicting both in-hospital and 1-year mortality than the first SHR. Adding the maximum SHR to the SOFA score could significantly improve the prognostic prediction. In the landmark analysis at 30 days, the maximum SHR was a risk factor for mortality within 30 days regardless of whether patients had diabetes. However, it was no longer associated with mortality after 30 days in patients with diabetes after adjustment (HR = 1.237 per 1-point increment, 95 % CI 0.854-1.790). CONCLUSIONS: The maximum SHR was significantly associated with mortality in patients with ACS hospitalized in the ICU. However, caution is warranted if it is used for predicting mortality after 30 days in patients with diabetes.


Assuntos
Síndrome Coronariana Aguda , Diabetes Mellitus , Hiperglicemia , Humanos , Estudos Retrospectivos , Síndrome Coronariana Aguda/complicações , Hiperglicemia/complicações , Hospitalização , Prognóstico
8.
Sci Rep ; 14(1): 3823, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360784

RESUMO

Zebrafish have been utilized for many years as a model animal for pharmacological studies on diabetes and obesity. High-fat diet (HFD), streptozotocin and alloxan injection, and glucose immersion have all been used to induce diabetes and obesity in zebrafish. Currently, studies commonly used both male and female zebrafish, which may influence the outcomes since male and female zebrafish are biologically different. This study was designed to investigate the difference between the metabolites of male and female diabetic zebrafish, using limonene - a natural product which has shown several promising results in vitro and in vivo in treating diabetes and obesity-and provide new insights into how endogenous metabolites change following limonene treatment. Using HFD-fed male and female zebrafish, we were able to develop an animal model of T2D and identify several endogenous metabolites that might be used as diagnostic biomarkers for diabetes. The endogenous metabolites in males and females were different, even though both genders had high blood glucose levels and a high BMI. Treatment with limonene prevented high blood glucose levels and improved in diabesity zebrafish by limonene, through reversal of the metabolic changes caused by HFD in both genders. In addition, limonene was able to reverse the elevated expression of AKT during HFD.


Assuntos
Diabetes Mellitus , Hiperglicemia , Animais , Feminino , Masculino , Hipoglicemiantes/farmacologia , Limoneno , Peixe-Zebra/metabolismo , Glicemia/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Obesidade/metabolismo , Dieta Hiperlipídica , Hiperglicemia/complicações
9.
Sci Rep ; 14(1): 3244, 2024 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-38332164

RESUMO

Target identification is a crucial step in elucidating the mechanisms by which functional food components exert their functions. Here, we identified the G-protein-coupled bile acid receptor 1 (GPBAR1, also known as TGR5) as a target of the triterpenoid mogrol, a class of aglycone mogroside derivative from Siraitia grosvenorii. Mogrol, but not mogrosides, activated cAMP-response element-mediated transcription in a TGR5-dependent manner. Additionally, mogrol selectively activated TGR5 but not the other bile acid-responsive receptors (i.e., farnesoid X receptor, vitamin D receptor, or muscarinic acetylcholine receptor M3). Several amino acids in TGR5 (L71A2.60, W75AECL1, Q77AECL1, R80AECL1, Y89A3.29, F161AECL2, L166A5.39, Y240A6.51, S247A6.58, Y251A6.62, L262A7.35, and L266A7.39) were found to be important for mogrol-induced activation. Mogrol activated insulin secretion under low-glucose conditions in INS-1 pancreatic ß-cells, which can be inhibited by a TGR5 inhibitor. Similar effects of mogrol on insulin secretion were observed in the isolated mouse islets. Mogrol administration partially but significantly alleviated hyperglycemia in KKAy diabetic mice by increasing the insulin levels without affecting the ß-cell mass or pancreatic insulin content. These results suggest that mogrol stimulates insulin secretion and alleviates hyperglycemia by acting as a TGR5 agonist.


Assuntos
Diabetes Mellitus Experimental , Hiperglicemia , Lanosterol/análogos & derivados , Fenantrenos , Camundongos , Animais , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Secreção de Insulina , Diabetes Mellitus Experimental/metabolismo , Insulina/metabolismo , Hiperglicemia/tratamento farmacológico , Proteínas de Ligação ao GTP/metabolismo , Ácidos e Sais Biliares
10.
Gut Microbes ; 16(1): 2310277, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38332701

RESUMO

Up to 40% of transplant recipients treated long-term with tacrolimus (TAC) develop post-transplant diabetes mellitus (PTDM). TAC is an important risk factor for PTDM, but is also essential for immunosuppression after transplantation. Long-term TAC treatment alters the gut microbiome, but the mechanisms of TAC-induced gut microbiota in the pathogenesis of PTDM are poorly characterized. Here, we showed that vancomycin, an inhibitor of bacterial beta-glucuronidase (GUS), prevents TAC-induced glucose disorder and insulin resistance in mice. Metagenomics shows that GUS-producing bacteria are predominant and flourish in the TAC-induced hyperglycemia mouse model, with upregulation of intestinal GUS activity. Targeted metabolomics analysis revealed that in the presence of high GUS activity, the hydrolysis of bile acid (BAs)-glucuronic conjugates is increased and most BAs are overproduced in the serum and liver, which, in turn, activates the ileal farnesoid X receptor (FXR) and suppresses GLP-1 secretion by L-cells. The GUS inhibitor vancomycin significantly eliminated GUS-producing bacteria and inhibited bacterial GUS activity and BAs levels, thereby enhancing L-cell GLP-1 secretion and preventing hyperglycemia. Our results propose a novel clinical strategy for inhibiting the bacterial GUS enzyme to prevent hyperglycemia without requiring withdrawal of TAC treatment. This strategy exerted its effect through the ileal bile acid-FXR-GLP-1 pathway.


Assuntos
Diabetes Mellitus , Microbioma Gastrointestinal , Hiperglicemia , Camundongos , Animais , Tacrolimo/farmacologia , Tacrolimo/uso terapêutico , Vancomicina/farmacologia , Imunossupressores/uso terapêutico , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Bactérias/genética , Bactérias/metabolismo , Glucuronidase/metabolismo , Glucuronidase/farmacologia , Ácidos e Sais Biliares/farmacologia , Peptídeo 1 Semelhante ao Glucagon
11.
Cardiovasc Diabetol ; 23(1): 61, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336720

RESUMO

BACKGROUND: Stress hyperglycemia and glycemic variability (GV) can reflect dramatic increases and acute fluctuations in blood glucose, which are associated with adverse cardiovascular events. This study aimed to explore whether the combined assessment of the stress hyperglycemia ratio (SHR) and GV provides additional information for prognostic prediction in patients with coronary artery disease (CAD) hospitalized in the intensive care unit (ICU). METHODS: Patients diagnosed with CAD from the Medical Information Mart for Intensive Care-IV database (version 2.2) between 2008 and 2019 were retrospectively included in the analysis. The primary endpoint was 1-year mortality, and the secondary endpoint was in-hospital mortality. Levels of SHR and GV were stratified into tertiles, with the highest tertile classified as high and the lower two tertiles classified as low. The associations of SHR, GV, and their combination with mortality were determined by logistic and Cox regression analyses. RESULTS: A total of 2789 patients were included, with a mean age of 69.6 years, and 30.1% were female. Overall, 138 (4.9%) patients died in the hospital, and 404 (14.5%) patients died at 1 year. The combination of SHR and GV was superior to SHR (in-hospital mortality: 0.710 vs. 0.689, p = 0.012; 1-year mortality: 0.644 vs. 0.615, p = 0.007) and GV (in-hospital mortality: 0.710 vs. 0.632, p = 0.004; 1-year mortality: 0.644 vs. 0.603, p < 0.001) alone for predicting mortality in the receiver operating characteristic analysis. In addition, nondiabetic patients with high SHR levels and high GV were associated with the greatest risk of both in-hospital mortality (odds ratio [OR] = 10.831, 95% confidence interval [CI] 4.494-26.105) and 1-year mortality (hazard ratio [HR] = 5.830, 95% CI 3.175-10.702). However, in the diabetic population, the highest risk of in-hospital mortality (OR = 4.221, 95% CI 1.542-11.558) and 1-year mortality (HR = 2.013, 95% CI 1.224-3.311) was observed in patients with high SHR levels but low GV. CONCLUSIONS: The simultaneous evaluation of SHR and GV provides more information for risk stratification and prognostic prediction than SHR and GV alone, contributing to developing individualized strategies for glucose management in patients with CAD admitted to the ICU.


Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus , Hiperglicemia , Humanos , Feminino , Idoso , Masculino , Doença da Artéria Coronariana/diagnóstico , Estudos Retrospectivos , Glicemia/análise , Fatores de Risco
12.
Cardiovasc Diabetol ; 23(1): 59, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38336786

RESUMO

BACKGROUND: The stress hyperglycaemic ratio (SHR), a new marker that reflects the true hyperglycaemic state of patients with acute coronary syndrome (ACS), is strongly associated with adverse clinical outcomes in these patients. Studies on the relationship between the SHR and in-hospital cardiac arrest (IHCA) incidence are limited. This study elucidated the relationship between the SHR and incidence of IHCA in patients with ACS. METHODS: In total, 1,939 patients with ACS who underwent percutaneous coronary intervention (PCI) at the Affiliated Hospital of Zunyi Medical University were included. They were divided into three groups according to the SHR: group T1 (SHR ≤ 0.838, N = 646), group T2 (0.838< SHR ≤ 1.140, N = 646), and group T3 (SHR3 > 1.140, N = 647). The primary endpoint was IHCA incidence. RESULTS: The overall IHCA incidence was 4.1% (N = 80). After adjusting for covariates, SHR was significantly associated with IHCA incidence in patients with ACS who underwent PCI (odds ratio [OR] = 2.6800; 95% confidence interval [CI] = 1.6200-4.4300; p<0.001), and compared with the T1 group, the T3 group had an increased IHCA risk (OR = 2.1800; 95% CI = 1.2100-3.9300; p = 0.0090). In subgroup analyses, after adjusting for covariates, patients with ST-segment elevation myocardial infarction (STEMI) (OR = 3.0700; 95% CI = 1.4100-6.6600; p = 0.0050) and non-STEMI (NSTEMI) (OR = 2.9900; 95% CI = 1.1000-8.1100; p = 0.0310) were at an increased IHCA risk. After adjusting for covariates, IHCA risk was higher in patients with diabetes mellitus (DM) (OR = 2.5900; 95% CI = 1.4200-4.7300; p = 0.0020) and those without DM (non-DM) (OR = 3.3000; 95% CI = 1.2700-8.5800; p = 0.0140); patients with DM in the T3 group had an increased IHCA risk compared with those in the T1 group (OR = 2.4200; 95% CI = 1.0800-5.4300; p = 0.0320). The restriction cubic spline (RCS) analyses revealed a dose-response relationship between IHCA incidence and SHR, with an increased IHCA risk when SHR was higher than 1.773. Adding SHR to the baseline risk model improved the predictive value of IHCA in patients with ACS treated with PCI (net reclassification improvement [NRI]: 0.0734 [0.0058-0.1409], p = 0.0332; integrated discrimination improvement [IDI]: 0.0218 [0.0063-0.0374], p = 0.0060). CONCLUSIONS: In patients with ACS treated with PCI, the SHR was significantly associated with the incidence of IHCA. The SHR may be a useful predictor of the incidence of IHCA in patients with ACS. The addition of the SHR to the baseline risk model had an incremental effect on the predictive value of IHCA in patients with ACS treated with PCI.


Assuntos
Síndrome Coronariana Aguda , Diabetes Mellitus , Parada Cardíaca , Hiperglicemia , Infarto do Miocárdio sem Supradesnível do Segmento ST , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST , Humanos , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Síndrome Coronariana Aguda/terapia , Estudos Retrospectivos , Hiperglicemia/diagnóstico , Hiperglicemia/epidemiologia , Hiperglicemia/complicações , Intervenção Coronária Percutânea/efeitos adversos , Incidência , Diabetes Mellitus/etiologia , Infarto do Miocárdio sem Supradesnível do Segmento ST/terapia , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Parada Cardíaca/diagnóstico , Parada Cardíaca/epidemiologia , Parada Cardíaca/terapia , Resultado do Tratamento , Fatores de Risco
13.
Cells ; 13(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38334628

RESUMO

Hyperglycemia, lipotoxicity, and insulin resistance are known to increase the secretion of extracellular matrix from cardiac fibroblasts as well as the activation of paracrine signaling from cardiomyocytes, immune cells, and vascular cells, which release fibroblast-activating mediators. However, their influences on vascular smooth muscle cells (vSMCs) have not been well examined. This study aimed to investigate whether contractile vascular vSMCs could develop a more synthetic phenotype in response to hyperglycemia. The results showed that contractile and synthetic vSMCs consumed high glucose in different ways. Lactate/GPR81 promotes the synthetic phenotype in vSMCs in response to high glucose levels. The stimulation of high glucose was associated with a significant increase in fibroblast-like features: synthetic vSMC marker expression, collagen 1 production, proliferation, and migration. GPR81 expression is higher in blood vessels in diabetic patients and in the high-glucose, high-lipid diet mouse. The results demonstrate that vSMCs assume a more synthetic phenotype when cultured in the presence of high glucose and, consequently, that the high glucose could trigger a vSMC-dependent cardiovascular disease mechanism in diabetes via lactate/GPR81.


Assuntos
Hiperglicemia , Músculo Liso Vascular , Animais , Humanos , Camundongos , Proliferação de Células , Células Cultivadas , Glucose/farmacologia , Glucose/metabolismo , Hiperglicemia/metabolismo , Ácido Láctico/metabolismo , Músculo Liso Vascular/metabolismo
14.
J Matern Fetal Neonatal Med ; 37(1): 2312447, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38350233

RESUMO

OBJECTIVE: The study aims to investigate the levels of serum NLRP3 along with its effector molecules (Caspase-1, IL-1ß, and IL-18) in the mid-pregnancy in pregnant women with hyperglycemia, and explore the relationship between NLRP3, along with its effector molecules (Caspase-1, IL-1ß, and IL-18) and insulin resistance, as well as pregnancy outcomes. METHODS: The levels of serum NLRP3 along with its effector molecules (Caspase-1, IL-1ß, and IL-18) in three groups of pregnant women with gestational diabetes mellitus (GDM), pregestational diabetes mellitus (PGDM) and normal glucose tolerance (NGT) were measured in mid-pregnancy, and their relationship with insulin resistance and pregnancy outcomes was analyzed. The ROC curve was also used to evaluate the predictive value of serum NLRP3 inflammasome and its effector molecules for pregnancy outcomes. RESULTS: There were no statistical differences in the general clinical data of the three groups, and the concentrations of serum NLRP3 along with its effector molecules were higher in the GDM and PGDM groups than in the NGT group, and NLRP3 along with its effector molecules were positively correlated with fasting blood glucose, fasting insulin, and insulin resistance index in both groups (r > 0, p < .05). The incidence of preterm delivery, hypertensive disorders of pregnancy, premature rupture of membranes, neonatal hypoglycemia and macrosomia was significantly higher in both groups than in the NGT group (p < .05). The value of the combined serum NLRP3 and its effector molecules in mid-pregnancy to predict adverse pregnancy outcomes was highest, and the AUCs for the combined prediction of late hypertensive disorders of pregnancy, premature rupture of membranes, preterm delivery, neonatal hypoglycemia and macrosomia were 0.84 (95% CI 0.79-0.88, p < .001), 0.81 (95% CI 0.75-0.85, p < .001), 0.76 (95% CI 0.70-0.81, p < .001), 0.76 (95% CI 0.70-0.81, p < .001) and 0.72 (95% CI 0.63-0.81, p < .001), respectively. CONCLUSIONS: Increased serum NLRP3 along with its effector molecules in pregnant women with hyperglycemia are associated with the levels of insulin resistance and the subsequent development of adverse pregnancy outcomes.


Assuntos
Diabetes Gestacional , Hiperglicemia , Hipertensão Induzida pela Gravidez , Hipoglicemia , Resistência à Insulina , Nascimento Prematuro , Recém-Nascido , Gravidez , Feminino , Humanos , Resultado da Gravidez/epidemiologia , Macrossomia Fetal/epidemiologia , Interleucina-18 , Nascimento Prematuro/epidemiologia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Glicemia , Hiperglicemia/complicações , Aumento de Peso , Caspases
15.
Int J Mol Sci ; 25(3)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38339087

RESUMO

Osteoarthritis (OA) is the most prevalent form of arthritis and a major cause of pain and disability. The pathology of OA involves the whole joint in an inflammatory and degenerative process, especially in articular cartilage. OA may be divided into distinguishable phenotypes including one associated with the metabolic syndrome (MetS) of which dyslipidemia and hyperglycemia have been individually linked to OA. Since their combined role in OA pathogenesis remains to be elucidated, we investigated the chondrocyte response to these metabolic stresses, and determined whether a n-3 polyunsaturated fatty acid (PUFA), i.e., eicosapentaenoic acid (EPA), may preserve chondrocyte functions. Rat chondrocytes were cultured with palmitic acid (PA) and/or EPA in normal or high glucose conditions. The expression of genes encoding proteins found in cartilage matrix (type 2 collagen and aggrecan) or involved in degenerative (metalloproteinases, MMPs) or in inflammatory (cyclooxygenase-2, COX-2 and microsomal prostaglandin E synthase, mPGES) processes was analyzed by qPCR. Prostaglandin E2 (PGE2) release was also evaluated by an enzyme-linked immunosorbent assay. Our data indicated that PA dose-dependently up-regulated the mRNA expression of MMP-3 and -13. PA also induced the expression of COX-2 and mPGES and promoted the synthesis of PGE2. Glucose at high concentrations further increased the chondrocyte response to PA. Interestingly, EPA suppressed the inflammatory effects of PA and glucose, and strongly reduced MMP-13 expression. Among the free fatty acid receptors (FFARs), FFAR4 partly mediated the EPA effects and the activation of FFAR1 markedly reduced the inflammatory effects of PA in high glucose conditions. Our findings demonstrate that dyslipidemia associated with hyperglycemia may contribute to OA pathogenesis and explains why an excess of saturated fatty acids and a low level in n-3 PUFAs may disrupt cartilage homeostasis.


Assuntos
Cartilagem Articular , Dislipidemias , Hiperglicemia , Osteoartrite , Ratos , Animais , Condrócitos/metabolismo , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/metabolismo , Ciclo-Oxigenase 2/metabolismo , Palmitatos/metabolismo , Células Cultivadas , Osteoartrite/metabolismo , Cartilagem Articular/metabolismo , Dinoprostona/metabolismo , Hiperglicemia/metabolismo , Glucose/farmacologia , Glucose/metabolismo , Dislipidemias/metabolismo
16.
Int J Mol Sci ; 25(3)2024 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-38339098

RESUMO

Diabetes mellitus is clinically defined by chronic hyperglycemia. Sex differences in the presentation and outcome of diabetes exist with premenopausal women having a reduced risk of developing diabetes, relative to men, or women after menopause. Accumulating evidence shows a protective role of estrogens, specifically 17-beta estradiol, in the maintenance of pancreatic beta cell health; however, the mechanisms underlying this protection are still unknown. To elucidate these potential mechanisms, we used a pancreatic beta cell line (BTC6) and a mouse model of hyperglycemia-induced atherosclerosis, the ApoE-/-:Ins2+/Akita mouse, exhibiting sexual dimorphism in glucose regulation. In this study we hypothesize that 17-beta estradiol protects pancreatic beta cells by modulating the unfolded protein response (UPR) in response to endoplasmic reticulum (ER) stress. We observed that ovariectomized female and male ApoE-/-:Ins2+/Akita mice show significantly increased expression of apoptotic UPR markers. Sham operated female and ovariectomized female ApoE-/-:Ins2+/Akita mice supplemented with exogenous 17-beta estradiol increased the expression of adaptive UPR markers compared to non-supplemented ovariectomized female ApoE-/-:Ins2+/Akita mice. These findings were consistent to what was observed in cultured BTC6 cells, suggesting that 17-beta estradiol may protect pancreatic beta cells by repressing the apoptotic UPR and enhancing the adaptive UPR activation in response to pancreatic ER stress.


Assuntos
Diabetes Mellitus , Hiperglicemia , Células Secretoras de Insulina , Humanos , Feminino , Camundongos , Masculino , Animais , Células Secretoras de Insulina/metabolismo , Estradiol/farmacologia , Estradiol/metabolismo , Resposta a Proteínas não Dobradas , Diabetes Mellitus/metabolismo , Estresse do Retículo Endoplasmático , Hiperglicemia/metabolismo , Apolipoproteínas E/metabolismo
17.
Sensors (Basel) ; 24(3)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38339464

RESUMO

The use of continuous glucose monitors (CGMs) in individuals living without diabetes is increasing. The purpose of this study was to profile various CGM metrics around nutritional intake, sleep and exercise in a large cohort of physically active men and women living without any known metabolic disease diagnosis to better understand the normative glycemic response to these common stimuli. A total of 12,504 physically active adults (age 40 ± 11 years, BMI 23.8 ± 3.6 kg/m2; 23% self-identified as women) wore a real-time CGM (Abbott Libre Sense Sport Glucose Biosensor, Abbott, USA) and used a smartphone application (Supersapiens Inc., Atlanta, GA, USA) to log meals, sleep and exercise activities. A total of >1 M exercise events and 274,344 meal events were analyzed. A majority of participants (85%) presented an overall (24 h) average glucose profile between 90 and 110 mg/dL, with the highest glucose levels associated with meals and exercise and the lowest glucose levels associated with sleep. Men had higher mean 24 h glucose levels than women (24 h-men: 100 ± 11 mg/dL, women: 96 ± 10 mg/dL). During exercise, the % time above >140 mg/dL was 10.3 ± 16.7%, while the % time <70 mg/dL was 11.9 ± 11.6%, with the remaining % within the so-called glycemic tight target range (70-140 mg/dL). Average glycemia was also lower for females during exercise and sleep events (p < 0.001). Overall, we see small differences in glucose trends during activity and sleep in females as compared to males and higher levels of both TAR and TBR when these active individuals are undertaking or competing in endurance exercise training and/or competitive events.


Assuntos
Hiperglicemia , Hipoglicemia , Masculino , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Glucose , Hipoglicemia/diagnóstico , Hiperglicemia/diagnóstico , Automonitorização da Glicemia , Glicemia/metabolismo
18.
Hum Brain Mapp ; 45(2): e26598, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339955

RESUMO

The network nature of the brain is gradually becoming a consensus in the neuroscience field. A set of highly connected regions in the brain network called "rich-club" are crucial high efficiency communication hubs in the brain. The abnormal rich-club organization can reflect underlying abnormal brain function and metabolism, which receives increasing attention. Diabetes is one of the risk factors for neurological diseases, and most individuals with prediabetes will develop overt diabetes within their lifetime. However, the gradual impact of hyperglycemia on brain structures, including rich-club organization, remains unclear. We hypothesized that the brain follows a special disrupted pattern of rich-club organization in prediabetes and diabetes. We used cross-sectional baseline data from the population-based PolyvasculaR Evaluation for Cognitive Impairment and vaScular Events (PRECISE) study, which included 2218 participants with a mean age of 61.3 ± 6.6 years and 54.1% females comprising 1205 prediabetes, 504 diabetes, and 509 normal control subjects. The rich-club organization and network properties of the structural networks derived from diffusion tensor imaging data were investigated using a graph theory approach. Linear mixed models were used to assess associations between rich-club organization disruptions and the subjects' glucose status. Based on the graphical analysis methods, we observed the disrupted pattern of rich-club organization was from peripheral regions mainly located in frontal areas to rich-club regions mainly located in subcortical areas from prediabetes to diabetes. The rich-club organization disruptions were associated with elevated glucose levels. These findings provided more details of the process by which hyperglycemia affects the brain, contributing to a better understanding of the potential neurological consequences. Furthermore, the disrupted pattern observed in rich-club organization may serve as a potential neuroimaging marker for early detection and monitoring of neurological disorders in individuals with prediabetes or diabetes.


Assuntos
Conectoma , Hiperglicemia , Estado Pré-Diabético , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Masculino , Imagem de Tensor de Difusão/métodos , Estado Pré-Diabético/diagnóstico por imagem , Estudos Transversais , Encéfalo/diagnóstico por imagem , Glucose , Vias Neurais
19.
BMJ Paediatr Open ; 8(1)2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341196

RESUMO

OBJECTIVE: To explore the glucose-related hormone profile of very low birthweight (VLBW) infants and assess the association between neonatal hyperglycaemia and insulin resistance during the admission period. DESIGN: A prospective observational study-the Very Low Birth Weight Infants, Glucose and Hormonal Profiles over Time study. SETTING: A tertiary neonatal intensive care unit and four neonatal units in county hospitals in Sweden. PATIENTS: 48 infants born <1500 g (VLBW) during 2016-2019. OUTCOME MEASURES: Plasma concentrations of glucose-related hormones and proteins (C-peptide, insulin, ghrelin, glucagon-like peptide 1 (GLP-1), glucagon, leptin, resistin and proinsulin), insulin:C-peptide and proinsulin:insulin ratios, Homoeostatic Model Assessment 2 (HOMA2) and Quantitative Insulin Sensitivity Check (QUICKI) indices, measured on day of life (DOL) 7 and at postmenstrual age 36 weeks. RESULTS: Lower gestational age was significantly associated with higher glucose, C-peptide, insulin, proinsulin, leptin, ghrelin, resistin and GLP-1 concentrations, increased HOMA2 index, and decreased QUICKI index and proinsulin:insulin ratio. Hyperglycaemic infants had significantly higher glucose, C-peptide, insulin, leptin and proinsulin concentrations, and lower QUICKI index, than normoglycaemic infants. Higher glucose and proinsulin concentrations and insulin:C-peptide ratio, and lower QUICKI index on DOL 7 were significantly associated with longer duration of hyperglycaemia during the admission period. CONCLUSIONS: VLBW infants seem to have a hormone profile consistent with insulin resistance. Lower gestational age and hyperglycaemia are associated with higher concentrations of insulin resistance markers.


Assuntos
Hiperglicemia , Resistência à Insulina , Recém-Nascido , Humanos , Lactente , Proinsulina , Leptina , Grelina , Resistina , Estudos Prospectivos , Peptídeo C , Glicemia/metabolismo , Insulina/metabolismo , Recém-Nascido de muito Baixo Peso , Peptídeo 1 Semelhante ao Glucagon , Hiperglicemia/epidemiologia , Insulina Regular Humana
20.
Cardiovasc Diabetol ; 23(1): 67, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38350936

RESUMO

BACKGROUND: Recent studies highlighted that stress hyperglycemia ratio (SHR) is a potential predictor for future risk in heart failure (HF) patients. However, its implications specifically in HF with preserved ejection fraction (HFpEF) are not yet fully elucidated. We aimed to investigate the association between SHR and long-term clinical outcomes in HFpEF patients. METHODS: HFpEF patients enrolled between 2015 and 2023, were followed (mean 41 months) for a composite outcome of all-cause, cardiovascular mortality, and HF rehospitalization. SHR was established as the ratio of acute-chronic glycemia from admission blood glucose and glycated hemoglobin. The optimal cut-off for SHR to predict outcomes based on event prediction was determined through ROC analysis, and the cutoff was identified at 0.99. The effect of SHR on adverse risk was examined through the Cox hazards and Kaplan-Meier survival methods. A Pearson correlation analysis was conducted to assess the relationship between SHR and the severity of HF, as indicated by N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Furthermore, the incremental prognostic value of SHR was further assessed by the integrated discrimination improvement (IDI) and the net reclassification improvement (NRI). RESULTS: Among the 400 enrolled patients, 190 individuals (47.5%) encountered composite events over the 41-month follow-up period. SHR was significantly elevated in patients with events compared with those without (p < 0.001). All patients were stratified into high SHR (n = 124) and low SHR (n = 276) groups based on the SHR cutoff. The high SHR group had a significantly higher incidence of adverse events than the low SHR group (log-rank; p < 0.001). Additional analysis indicated a poorer prognosis in patients with low left ventricular EF (LVEF) levels (50 < LVEF < 60) and high SHR (SHR > 0.99) in comparison to the other groups (log-rank p < 0.001). In adjusted analysis, after accounting for age, sex, diabetes, and NT-proBNP, elevated SHR remained independently predictive of adverse outcomes (adjusted HR: 2.34, 95% CI 1.49-3.67; p < 0.001). Furthermore, adding SHR to a model with MAGGIC score provided an incremental improvement in predicting adverse events. Additionally, SHR displayed a slight correlation with NT-proBNP. CONCLUSION: Elevated SHR was independently associated with an increased risk for composite events of all-cause, cardiovascular mortality, and HF readmission than those with lower SHR. SHR is a valuable tool for predicting and stratifying long-term adverse risks among HFpEF patients.


Assuntos
Insuficiência Cardíaca , Hiperglicemia , Humanos , Prognóstico , Volume Sistólico , Biomarcadores , Hiperglicemia/diagnóstico , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos
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