RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Persian medicine (TPM), people often use herbal infusions as a dosage form to treat diseases related to hyperglycemia, known as 'dam-kardeh'. Traditionally, herbal preparations of Eryngium bungei Boiss. (E. b), Tragopogon buphthalmoides (DC.) Boiss. (T. b), Salvia hydrangea DC. ex Benth. (S. h), and Juniperus polycarpos K. Koch. (J. p) are used to manage diabetes in Iran. However, there is no evidence of their effectiveness in controlling glucose levels and their mechanisms remain unclear. AIM OF THE STUDY: This study aimed to investigate whether traditional doses of plant infusions can have hypoglycemic and/or anti-hyperglycemic effects during fasting and/or postprandial states and establish the basis for future research on their potential mechanisms of action. MATERIALS AND METHODS: The effects of traditional doses of herbal extracts on blood glucose levels in STZ-NA-induced hyperglycemic rats were investigated in 2-h acute tests during fasting and postprandial states (with a glucose load). In addition, the potential inhibitory effect in vitro of enzymes involved in relevant pathways, such as gluconeogenesis (fructose-1,6-bisphosphatase, FBPase and glucose-6-phosphatase, G6Pase), carbohydrate breakdown (intestinal α-glucosidases), and insulin sensitivity (protein tyrosine phosphatase 1B, PTP-1B) was evaluated. Acute toxicity tests were carried out and HPLC-SQ-TOF was used to analyze the chemical profiles of the plant extracts. RESULTS: In the fasting state, T. b, S. h, and E. b were as effective as glibenclamide in lowering blood glucose levels in hyperglycemic rats. Moreover, all three suppressed G6Pase and FBPase enzymatic activity by 90-97% and 80-91%, respectively. On the other hand, significant postprandial hypoglycemic efficacy was observed for E. b, S. h, and T. b. Based on the AUC values, T. b caused a reduction comparable to the therapeutic efficacy of repaglinide. When investigating the possible mechanisms of action involved in this activity, E. b, S. h, and T. b showed significant inhibition of PTP-1B in vitro (>70%). Finally, all plant extracts showed no signs of acute toxicity. Several compounds that may contribute to biological activities were identified, including phenolic acids and flavonoid glycosides. CONCLUSIONS: The present study supports the traditional use of T. b, E. b and S. h for the control of diabetes in the fasting and postprandial state. Moreover, these plants were found to be rich in bioactive compounds with hypoglycemic and antihyperglycemic activities. On the other hand, J. p, showed a modest effect only in the fasting state and after 90 min. Further studies are needed to expand these results by analyzing the chemical composition and using complementary experimental models.

Asunto(s)

Glucemia , Diabetes Mellitus Experimental , Ayuno , Hipoglucemiantes , Extractos Vegetales , Periodo Posprandial , Animales , Hipoglucemiantes/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/sangre , Masculino , Irán , Ratas , Medicina Persa , Ratas Wistar , Hiperglucemia/tratamiento farmacológico , Plantas Medicinales/química , Estreptozocina , Juniperus/química

RESUMEN

Background: The stress hyperglycemia ratio (SHR) has emerged as a potential prognostic indicator for various critical illnesses. However, its role in determining outcomes in patients with atrial fibrillation (AF) within the intensive care unit (ICU) remains unclear. This study aimed to elucidate the association between SHR and all-cause mortality in this clinical setting. Methods: We conducted a retrospective cohort study utilizing data from a large, retrospective database. Critically ill patients with documented AF were stratified based on quartiles of SHR. The primary outcome was 365-day all-cause mortality, with secondary outcomes including 90-day and 28-day mortality. COX proportional hazards models adjusted for confounders and Kaplan-Meier curve analyses were used to explore the relationship between SHR and mortality. Results: 2,679 patients with critical AF were enrolled in the final study. Among the patients studied, those in the highest SHR quartiles exhibited an increased risk of 365-day all-cause mortality (HR:1.32, 95%CI=1.06-1.65). Notably, in subgroup analyses, the prognostic value of SHR was particularly pronounced in patients with hypertension. Sensitivity analyses confirmed the persistence of these findings after excluding cohorts with malignant tumors, and heart failure. Conclusions: Our research discerns a positive association between SHR and all-cause mortality in critically ill patients with AF, highlighting the significance of acute glycemic dysregulation on patient outcomes. Longer follow-up is still needed in the future to study the association between SHR and all-cause mortality in critically ill patients with AF.

Asunto(s)

Fibrilación Atrial , Enfermedad Crítica , Hiperglucemia , Humanos , Fibrilación Atrial/mortalidad , Fibrilación Atrial/sangre , Enfermedad Crítica/mortalidad , Masculino , Femenino , Anciano , Estudios Retrospectivos , Hiperglucemia/mortalidad , Hiperglucemia/sangre , Persona de Mediana Edad , Pronóstico , Glucemia/análisis , Glucemia/metabolismo , Unidades de Cuidados Intensivos/estadística & datos numéricos , Anciano de 80 o más Años

RESUMEN

Acute ischemic stroke (AIS) is a major global health concern due to its high mortality and disability rates. Hemorrhagic transformation, a common complication of AIS, leads to poor prognosis yet lacks effective treatments. Preclinical studies indicate that hyperbaric oxygen (HBO) treatment within 12 h of AIS onset alleviates ischemia/reperfusion injuries, including hemorrhagic transformation. However, clinical trials have yielded conflicting results, suggesting some underlying mechanisms remain unclear. In this study, we confirmed that HBO treatments beginning within 1 h post reperfusion significantly alleviated the haemorrhage and neurological deficits in hyperglycemic transient middle cerebral arterial occlusion (tMCAO) mice, partly due to the inhibition of the NLRP3 inflammasome-mediated pro-inflammatory response in microglia. Notably, reactive oxygen species (ROS) mediate the anti-inflammatory and protective effect of early HBO treatment, as edaravone and N-Acetyl-L-Cysteine (NAC), two commonly used antioxidants, reversed the suppressive effect of HBO treatment on NLRP3 inflammasome-mediated inflammation in microglia. Furthermore, NAC countered the protective effect of early HBO treatment in tMCAO mice with hyperglycemia. These findings support that early HBO treatment is a promising intervention for AIS, however, caution is warranted when combining antioxidants with HBO treatment. Further assessments are needed to clarify the role of antioxidants in HBO therapy for AIS.

Asunto(s)

Oxigenoterapia Hiperbárica , Hiperglucemia , Microglía , Especies Reactivas de Oxígeno , Animales , Microglía/metabolismo , Microglía/efectos de los fármacos , Oxigenoterapia Hiperbárica/métodos , Ratones , Especies Reactivas de Oxígeno/metabolismo , Hiperglucemia/metabolismo , Hiperglucemia/complicaciones , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Inflamasomas/metabolismo , Modelos Animales de Enfermedad , Accidente Cerebrovascular/terapia , Accidente Cerebrovascular/metabolismo , Antioxidantes/farmacología , Ratones Endogámicos C57BL , Infarto de la Arteria Cerebral Media/terapia , Edaravona/farmacología , Daño por Reperfusión/metabolismo

RESUMEN

Background: Endogenous insulin supplementation is essential for individuals with type 1 diabetes (T1D). However, current treatments, including pancreas transplantation, insulin injections, and oral medications, have significant limitations. The development of engineered cells that can secrete endogenous insulin offers a promising new therapeutic strategy for type 1 diabetes (T1D). This approach could potentially circumvent autoimmune responses associated with the transplantation of differentiated ß-cells or systemic delivery of viral vectors. Methods: We utilized CRISPR/Cas9 gene editing coupled with homology-directed repair (HDR) to precisely integrate a promoter-free EMCVIRES-insulin cassette into the 3' untranslated region (UTR) of the GAPDH gene in human HEK-293T cells. Subsequently quantified insulin expression levels in these engineered cells, the viability and functionality of the engineered cells when seeded on different cell vectors (GelMA and Cytopore I) were also assessed. Finally, we investigated the therapeutic potential of EMCVIRES-based insulin secretion circuits in reversing Hyperglycaemia in T1D mice. Result: Our results demonstrate that HDR-mediated gene editing successfully integrated the IRES-insulin loop into the genome of HEK-293T cells, a non-endocrine cell line, enabling the expression of human-derived insulin. Furthermore, Cytopore I microcarriers facilitated cell attachment and proliferation during in vitro culture and enhanced cell survival post-transplantation. Transplantation of these cell-laden microcarriers into mice led to the development of a stable, fat-encapsulated structure. This structure exhibited the expression of the platelet-endothelial cell adhesion molecule CD31, and no significant immune rejection was observed throughout the experiment. Diabetic mice that received the cell carriers reversed hyperglycemia, and blood glucose fluctuations under simulated feeding stimuli were very similar to those of healthy mice. Conclusion: In summary, our study demonstrates that Cytopore I microcarriers are biocompatible and promote long-term cell survival in vivo. The promoter-free EMCVIRES-insulin loop enables non-endocrine cells to secrete mature insulin, leading to a rapid reduction in glucose levels. We have presented a novel promoter-free genetic engineering strategy for insulin secretion and proposed an efficient cell transplantation method. Our findings suggest the potential to expand the range of cell sources available for the treatment of diabetes, offering new avenues for therapeutic interventions.

Asunto(s)

Diabetes Mellitus Tipo 1 , Edición Génica , Hiperglucemia , Células Secretoras de Insulina , Insulina , Humanos , Animales , Hiperglucemia/terapia , Hiperglucemia/metabolismo , Ratones , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Insulina/genética , Células HEK293 , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/genética , Edición Génica/métodos , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/genética , Sitios Internos de Entrada al Ribosoma/genética , Regiones Promotoras Genéticas , Sistemas CRISPR-Cas

RESUMEN

Background: Effective glycemic control is crucial for hospitalized patients, leading to benefits such as shorter hospital stays and reduced postoperative infection rates. While previous studies have emphasized the effectiveness of multidisciplinary collaborative stewardship for hospital-wide hyperglycemia management, patient perspectives and preferences have not been adequately considered. Objective: To identify factors influencing treatment preferences of Chinese hospitalized diabetes patients using discrete choice experiments (DCEs) and provide practical insights for the construction of a hospital-wide glycemic control programme. Methods: A face-to-face survey was conducted among diabetes patients admitted to nonendocrine departments in a tertiary hospital in Nanjing, China. The attributes and levels were determined based on DCE principles, and a conditional logit model was used to quantify patients' preferences. Results: A total of 157 respondents were analyzed. Antihyperglycemic effectiveness, healthcare providers, treatment regimen, monitoring frequency, and adverse reactions were the five attributes that significantly influenced patient preference (p < 0.05). Notably, an 80% glycemic control rate (ß = 2.009) and a multidisciplinary management team involving clinical pharmacists (ß = 1.346) had the greatest impact. Negative effects were observed for hypoglycemia (ß = -1.008), insulin pump use (ß = -0.746), and frequent glucose monitoring (ß = -0.523). Female patients exhibited higher concern for healthcare providers (ß = 1.172) compared to males. Younger and shorter-course patients prioritized antihyperglycemic effectiveness (ß = 3.330, ß = 1.510), while older patients preferred multidisciplinary management (ß = 1.186) and opposed increased monitoring frequency (ß = -0.703). Patients with higher educational backgrounds showed greater acceptance of continuous glucose monitoring (ß = 1.983), and those with higher annual income placed more emphasis on glycemic control rate. Conclusion: Treatment preferences of hospitalized diabetes patients are mainly influenced by antihyperglycemic effectiveness, adverse reactions, healthcare providers, and individual characteristics. Comprehensive consideration and an individualized therapy strategy should be given when constructing a hospital-wide glycemic control programme.

Asunto(s)

Glucemia , Diabetes Mellitus , Control Glucémico , Hospitalización , Hipoglucemiantes , Prioridad del Paciente , Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Hipoglucemiantes/uso terapéutico , China , Diabetes Mellitus/terapia , Diabetes Mellitus/sangre , Glucemia/metabolismo , Adulto , Conducta de Elección , Encuestas y Cuestionarios , Hiperglucemia

RESUMEN

BACKGROUND: We investigated the impacts of tocolytic agents on maternal and neonatal blood glucose levels in women with gestational diabetes mellitus (GDM) who used tocolytics for preterm labor. METHODS: This multi-center, retrospective cohort study included women with GDM who were admitted for preterm labor from twelve hospitals in South Korea. We excluded women with multiple pregnancies, anomalies, overt DM diagnosed before pregnancy or 23 weeks of gestation, and women who received multiple tocolytics. The patients were divided according to the types of tocolytics; atosiban, ritodrine, and nifedipine group. We collected baseline maternal characteristics, pregnancy outcomes, maternal glucose levels during hospitalization, and neonatal glucose levels. We compared the frequency of maternal hyperglycemia and neonatal hypoglycemia among three groups. A multivariate logistic regression analysis was performed to evaluate the contributing factors to the occurrence of maternal hyperglycemia and neonatal hypoglycemia. RESULTS: A total of 128 women were included: 44 (34.4%), 51 (39.8%), and 33 (25.8%) women received atosiban, ritodrine, and nifedipine, respectively. Mean fasting blood glucose (FBG) (112.3, 109.6, and 89.5 mg/dL, P < 0.001) and 2-hour postprandial glucose (PPG2) levels (145.4, 148.3, and 116.5 mg/dL, P = 0.004) were significantly higher in atosiban and ritodrine group than those in nifedipine group. Even after adjusting for covariates including antenatal steroid use, gestational age at admission, and pre-pregnancy body mass index, there was an increased risk of high maternal mean FBG (≥ 95 mg/dL) and PPG2 (≥ 120 mg/dL) levels in the atosiban and ritodrine group than in nifedipine group. The atosiban and ritodrine groups are also at increased risk of neonatal hypoglycemia (< 47 mg/dL) compared to the nifedipine group with the odds ratio of 4.58 and 4.67, respectively (P < 0.05). CONCLUSION: There is an increased risk of maternal hyperglycemia and neonatal hypoglycemia in women with GDM using atosiban and ritodrine tocolytics for preterm labor compared to those using nifedipine.

Asunto(s)

Glucemia , Diabetes Gestacional , Hipoglucemia , Nifedipino , Ritodrina , Tocolíticos , Vasotocina , Humanos , Femenino , Embarazo , Diabetes Gestacional/tratamiento farmacológico , Tocolíticos/uso terapéutico , Tocolíticos/efectos adversos , Glucemia/análisis , Estudios Retrospectivos , Adulto , Nifedipino/uso terapéutico , Nifedipino/efectos adversos , Recién Nacido , Ritodrina/uso terapéutico , Ritodrina/efectos adversos , Vasotocina/análogos & derivados , Vasotocina/uso terapéutico , Vasotocina/efectos adversos , Modelos Logísticos , Hiperglucemia/tratamiento farmacológico , Oportunidad Relativa , Trabajo de Parto Prematuro/tratamiento farmacológico , Resultado del Embarazo , República de Corea

RESUMEN

BACKGROUND: Critically ill patients in the intensive care unit (ICU) often experience dysglycaemia. However, studies investigating the link between acute kidney injury (AKI) and dysglycaemia, especially in those with and without diabetes mellitus (DM), are limited. METHODS: We used the Medical Information Mart for Intensive Care IV database to investigate the association between AKI within 7 days of admission and subsequent dysglycaemia. The primary outcome was the occurrence of dysglycaemia (both hypoglycemia and hyperglycemia) after 7 days of ICU admission. Logistic regression analyzed the relationship between AKI and dysglycaemia, while a Cox proportional hazards model estimated the long-term mortality risk linked to the AKI combined with dysglycaemia. RESULTS: A cohort of 20,008 critically ill patients were included. The AKI group demonstrated a higher prevalence of dysglycaemia, compared to the non-AKI group. AKI patients had an increased risk of dysglycaemia (adjusted odds ratio [aOR] 1.53, 95% confidence interval [CI] 1.41-1.65), hypoglycemia (aOR 1.56, 95% CI 1.41-1.73), and hyperglycemia (aOR 1.53, 95% CI 1.41-1.66). In subgroup analysis, compared to DM patients, AKI showed higher risk of dysglycaemia in non-DM patients (aOR: 1.93 vs. 1.33, Pint<0.01). Additionally, the AKI with dysglycaemia group exhibited a higher risk of long-term mortality compared to the non-AKI without dysglycaemia group. Dysglycaemia also mediated the relationship between AKI and long-term mortality. CONCLUSION: AKI was associated with a higher risk of dysglycaemia, especially in non-DM patients, and the combination of AKI and dysglycaemia was linked to higher long-term mortality. Further research is needed to develop optimal glycemic control strategies for AKI patients.

Asunto(s)

Lesión Renal Aguda , Enfermedad Crítica , Hiperglucemia , Hipoglucemia , Unidades de Cuidados Intensivos , Humanos , Lesión Renal Aguda/sangre , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/etiología , Lesión Renal Aguda/epidemiología , Masculino , Estudios Retrospectivos , Femenino , Enfermedad Crítica/mortalidad , Persona de Mediana Edad , Anciano , Hiperglucemia/complicaciones , Hiperglucemia/sangre , Hiperglucemia/epidemiología , Hipoglucemia/complicaciones , Hipoglucemia/sangre , Hipoglucemia/epidemiología , Hipoglucemia/mortalidad , Unidades de Cuidados Intensivos/estadística & datos numéricos , Diabetes Mellitus/epidemiología , Factores de Riesgo , Modelos Logísticos , Modelos de Riesgos Proporcionales , Glucemia/análisis , Prevalencia

RESUMEN

The stress hyperglycemia ratio (SHR) is established as a reliable marker for assessing the severity of stress-induced hyperglycemia. While its effectiveness in managing patients with Acute Ischemic Stroke (AIS) remains to be fully understood. We aim to explore the relationship between SHR and clinical prognosis in AIS patients and to assess how diabetes status influences this relationship. In this study, we analyzed data from the Medical Information Mart for Intensive Care (MIMIC-IV) database, selecting patients with AIS who required ICU admission. These patients were categorized into tertiles based on their SHR levels. We applied Cox hazard regression models and used restricted cubic spline (RCS) curves to investigate relationships between outcomes and SHR. The study enrolled a total of 2029 patients. Cox regression demonstrated that a strong correlation was found between increasing SHR levels and higher all-cause mortality. Patients in the higher two tertiles of SHR experienced significantly elevated 30-day and 90-day mortality rates compared to those in the lowest tertile. This pattern remained consistent regardless of diabetes status. Further, RCS analysis confirmed a progressively increasing risk of all-cause mortality with higher SHR levels. The findings indicate that SHR is association with increased 30-day and 90-day mortality among AIS patients, underscoring its potential value in risk stratification. Although the presence of diabetes may weaken this association, significant correlations persist in diabetic patients.

Asunto(s)

Hiperglucemia , Accidente Cerebrovascular Isquémico , Humanos , Masculino , Femenino , Anciano , Accidente Cerebrovascular Isquémico/mortalidad , Accidente Cerebrovascular Isquémico/sangre , Accidente Cerebrovascular Isquémico/complicaciones , Hiperglucemia/mortalidad , Hiperglucemia/complicaciones , Hiperglucemia/sangre , Persona de Mediana Edad , Pronóstico , Anciano de 80 o más Años , Modelos de Riesgos Proporcionales , Glucemia/análisis , Factores de Riesgo

RESUMEN

BACKGROUND: Helicobacter pylori colonizes the human stomach and may affect the inflammatory response, hormone production related to energy regulation, and gastrointestinal microbiota composition. Previous studies have explored a potential association between H. pylori infection and pediatric obesity with varying results. Considering the immunomodulatory effects of early-life infection with H. pylori that can confer beneficial effects, we hypothesized that we would find an inverse relationship between H. pylori seropositivity and obesity among Danish children and adolescents. METHODS: We assessed H. pylori seroprevalence in 713 subjects from an obesity clinic cohort and 990 subjects from a population-based cohort, aged 6 to 19 years, and examined its association with obesity and other cardiometabolic risk factors. RESULTS: No association was found between H. pylori and body mass index standard deviation score (BMI SDS). H. pylori seropositivity was, however, significantly associated with higher fasting plasma glucose levels and the prevalence of hyperglycemia. CONCLUSION: While we did not find an association between H. pylori seropositivity and BMI SDS, we observed a significant association with higher fasting plasma glucose levels and increased prevalence of hyperglycemia, suggesting that H. pylori infection may contribute to impaired glucose regulation in Danish children and adolescents.

Asunto(s)

Infecciones por Helicobacter , Helicobacter pylori , Hiperglucemia , Humanos , Adolescente , Niño , Dinamarca/epidemiología , Infecciones por Helicobacter/epidemiología , Infecciones por Helicobacter/sangre , Masculino , Femenino , Hiperglucemia/epidemiología , Hiperglucemia/sangre , Estudios Seroepidemiológicos , Adulto Joven , Obesidad Infantil/epidemiología , Obesidad Infantil/sangre , Obesidad Infantil/microbiología , Estudios de Cohortes , Índice de Masa Corporal , Prevalencia , Glucemia/análisis

RESUMEN

Background: In recent years, the incidence of Endometrial cancer (EC) has been on the rise due to high-fat, high-calorie diets and low-exercise lifestyles. However, the relationships between metabolic disorders and the progression of EC remain uncertain. The purpose of our study was to explore the potential association between obesity, hypertension, hyperglycemia and clinicopathologic characteristics in EC patients. Methods: In categorical variables, Chi-square tests were used to calculate P values. Univariate logistic regression and multivariate logistic regression were used to identify the risk factors of myometrial invasion>1/2 and lymph node metastasis. Overall survival (OS) was estimated using the Kaplan-Meier method. Results: The study included 406 individuals with EC, 62.6% had type I and 37.4% had type II. Hypertension was seen in 132 (32.5%), hyperglycemia in 75 (18.5%), and overweight or obesity in 217 (53.4%). Hypertension, hyperglycemia, and obesity are strongly associated with the clinicopathologic features of EC. Multivariate logistic regression revealed that hyperglycemia (OR=2.439,95% CI: 1.025-5.804, P = 0.044) was a risk factor for myometrial invasion depth >1/2 in patients with type I EC, and hypertension (OR=32.124,95% CI: 3.287-313.992, P = 0.003) was a risk factor for lymph node metastasis in patients with type I EC. Survival analysis found that hyperglycemia (P < 0.001) and hypertension (P = 0.002) were associated with OS in type I EC. Neither hyperglycemia, hypertension, nor obesity were associated with the prognosis in type II EC. Conclusion: Hyperglycemia was a risk factor for myometrial invasion depth >1/2 in patients with type I EC and hypertension was a risk factor for lymph node metastasis in patients with type I EC. Hypertension and hyperglycemia were associated with poor prognosis in patients with type I EC.

Asunto(s)

Neoplasias Endometriales , Hiperglucemia , Hipertensión , Humanos , Femenino , Neoplasias Endometriales/patología , Neoplasias Endometriales/complicaciones , Neoplasias Endometriales/mortalidad , Neoplasias Endometriales/epidemiología , Persona de Mediana Edad , Hiperglucemia/complicaciones , Hiperglucemia/epidemiología , Anciano , Hipertensión/complicaciones , Hipertensión/epidemiología , Factores de Riesgo , Obesidad/complicaciones , Metástasis Linfática , Pronóstico , Adulto , Enfermedades Metabólicas/epidemiología , Enfermedades Metabólicas/patología , Enfermedades Metabólicas/complicaciones , Estudios Retrospectivos

RESUMEN

The underlying mechanism of postoperative delirium (POD) in elderly people remains unclear. Perioperative hyperglycemia (POHG) is an independent risk indicator for POD, particularly in the elderly. Under cerebral desaturation (hypoxia) during general anesthesia, hypoxia-inducible factor (HIF) is neuroprotective during cerebral hypoxia via diverse pathways, like glucose metabolism and angiogenesis. Hyperglycemia can repress HIF expression and activity. On the other hand, POHG occurred among patients undergoing surgery. For surgical stress, hypothalamic-pituitary-adrenal activation and sympathoadrenal activation may increase endogenous glucose production via gluconeogenesis and glycogenolysis. Thus, under the setting of cerebral hypoxia during general anesthesia, we speculate that POHG prevents HIF-1α levels and function in the brain of aged patients, thus exacerbating the hypoxic response of HIF-1 and potentially contributing to POD. This paper sketches the underlying mechanisms of HIF in POD in elderly patients and offers novel insights into targets for preventing or treating POD in the same way as POHG.

Asunto(s)

Hiperglucemia , Complicaciones Posoperatorias , Humanos , Hiperglucemia/metabolismo , Hiperglucemia/etiología , Anciano , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/metabolismo , Complicaciones Posoperatorias/prevención & control , Delirio/etiología , Delirio/metabolismo , Delirio/prevención & control , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Factor 1 Inducible por Hipoxia/metabolismo , Anestesia General/efectos adversos

Asunto(s)

Hiperglucemia , Hemorragia Subaracnoidea , Humanos , Hemorragia Subaracnoidea/complicaciones , Hiperglucemia/complicaciones , Pronóstico , Estudios Retrospectivos , Glucemia

RESUMEN

One of the four main non-communicable illnesses, diabetes mellitus, calls for immediate attention from all key stakeholders worldwide to address its prevalence and related consequences. Hyperglycemia and hyperglycemic-induced oxidative stress and inflammation are thought as the third largest risk factor for early mortality throughout the globe, killing an estimated 1.6 million people annually. Hyperglycemia hyperglycemic-induced oxidative stress, inflammation, and the onset and progression of type 2 diabetes mellitus are all intricately connected. Several studies showed that subclinical inflammation adds to insulin resistance and is connected to the hallmarks of metabolic syndrome, including hyperglycemia, that increases the chance of developing type 2 diabetes. Inflammation increases the creation of reactive oxygen species, which will be later increased by oxidative stress. The fundamental impetus for this study was the recognition of the interplay between diabetes, oxidative stress, and inflammation. This literature review focuses on type 2 diabetes and selected diabetic complications, and it analyses the relationship between these diseases, as well as oxidative stress, inflammation, risk factors for developing diabetes, and the mechanisms behind hyperglycemia-induced oxidative stress.

Asunto(s)

Antioxidantes , Glucemia , Diabetes Mellitus Tipo 2 , Inflamación , Estrés Oxidativo , Humanos , Diabetes Mellitus Tipo 2/sangre , Antioxidantes/metabolismo , Glucemia/metabolismo , Hiperglucemia/sangre , Hiperglucemia/complicaciones , Hiperglucemia/metabolismo , Lípidos/sangre , Factores de Riesgo , Especies Reactivas de Oxígeno/metabolismo , Resistencia a la Insulina

RESUMEN

BACKGROUND: Stress-induced hyperglycemia (SIH) is associated with poor outcomes in cardiogenic shock (CS), and there have been inconsistent results among patients with or without diabetes mellitus (DM). The glycemic gap (GG) is derived by subtracting A1c-derived average glucose from blood glucose levels; it is a superior indicator of SIH. We aimed to explore the role of GG in the outcomes of patients with CS. METHODS: Data on patients diagnosed with CS were extracted from the MIMIC-IV v2.0 database to investigate the relationship between GG and 30-day mortality (Number of absolute GG subjects = 359; Number of relative GG subjects = 357). CS patients from the Second Affiliated Hospital of Wenzhou Medical University were enrolled to explore the correlation between GG and lactic acid (Number of absolute GG subjects = 252; Number of relative GG subjects = 251). Multivariate analysis, propensity score-matched (PSM) analysis, inverse probability treatment weighting (IPTW), and Pearson correlation analysis were applied. RESULTS: Absolute GG was associated with 30-day all-cause mortality in CS patients (HRadjusted: 1.779 95% CI: 1.137-2.783; HRPSM: 1.954 95% CI: 1.186-3.220; HRIPTW: 1.634 95% CI: 1.213-2.202). The higher the absolute GG level, the higher the lactic acid level (ßadjusted: 1.448 95% CI: 0.474-2.423). A similar trend existed in relative GG (HRadjusted: 1.562 95% CI: 1.003-2.432; HRPSM: 1.790 95% CI: 1.127-2.845; HRIPTW: 1.740 95% CI: 1.287-2.352; ßadjusted:1.294 95% CI: 0.369-2.219). Subgroup analysis showed that the relationship existed irrespective of DM. The area under the curve of GG combined with the Glasgow Coma Scale (GCS) for 30-day all-cause mortality was higher than that of GCS (absolute GG: 0.689 vs. 0.637; relative GG: 0.688 vs. 0.633). GG was positively related to the triglyceride-glucose index. Kaplan-Meier curves revealed that groups of higher GG with DM had the worst outcomes. The outcomes differed among races and GG levels (all P < 0.05). CONCLUSIONS: Among patients with CS, absolute and relative GGs were associated with increased 30-day all-cause mortality, regardless of DM. The relationship was stable after multivariate Cox regression analysis, PSM, and IPTW analysis. Furthermore, they reflect the severity of CS to some extent. Hyperlactatemia and insulin resistance may underlie the relationship between stress-induced hyperglycemia and poor outcomes in CS patients. They both improve the predictive efficacy of the GCS.

Asunto(s)

Biomarcadores , Glucemia , Hemoglobina Glucada , Hiperglucemia , Ácido Láctico , Choque Cardiogénico , Humanos , Choque Cardiogénico/mortalidad , Choque Cardiogénico/diagnóstico , Choque Cardiogénico/sangre , Choque Cardiogénico/terapia , Choque Cardiogénico/etiología , Masculino , Femenino , Estudios Retrospectivos , Glucemia/metabolismo , Persona de Mediana Edad , Anciano , Biomarcadores/sangre , Factores de Riesgo , Factores de Tiempo , Hiperglucemia/diagnóstico , Hiperglucemia/mortalidad , Hiperglucemia/sangre , Pronóstico , Hemoglobina Glucada/metabolismo , Ácido Láctico/sangre , China/epidemiología , Bases de Datos Factuales , Valor Predictivo de las Pruebas , Medición de Riesgo , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/mortalidad

RESUMEN

Neonatal encephalopathy (NE) is a serious condition with various neurological dysfunctions in newborns. Disruptions in glucose metabolism, including both hypoglycemia and hyperglycemia, are common in NE and can significantly impact outcomes. Hypoglycemia, defined as blood glucose below 45 mg/dL, is associated with increased mortality, neurodevelopmental disabilities, and brain lesions on MRI. Conversely, hyperglycemia, above 120 to 150 mg/dL, has also been linked to heightened mortality, hearing impairment, and multiorgan dysfunction. Both aberrant glucose states appear to worsen prognosis compared to normoglycemic infants. Therapeutic hypothermia is the standard of care for NE that provides neuroprotection by reducing metabolic demands and inflammation. Adjunct therapies like glucagon and continuous glucose monitoring show promise in managing dysglycemia and improving outcomes. Glucagon can enhance cerebral blood flow and glucose supply, while continuous glucose monitoring enables real-time monitoring and personalized interventions. Maintaining balanced blood sugar levels is critical in managing NE. Early detection and intervention of dysglycemia are crucial to improve outcomes in neonates with encephalopathy. Further research is needed to optimize glycemic management strategies and explore the potential benefits of interventions like glucagon therapy.

Asunto(s)

Encefalopatías , Hiperglucemia , Hipoglucemia , Humanos , Hipoglucemia/diagnóstico , Recién Nacido , Hiperglucemia/complicaciones , Encefalopatías/etiología , Encefalopatías/diagnóstico , Glucemia/metabolismo , Glucemia/análisis , Hipotermia Inducida/métodos

RESUMEN

BACKGROUND: Hyperglycemia is associated with adverse outcomes in patent with traumatic brain injury. There is convincing evidence of the deleterious effects of early systemic hyperglycemia on neurological outcomes and guides management toward intensive glycemic control. The purpose of this systematic review and meta analysis is to evaluate and summarize the level of evidence on the role of glycemic control in traumatic brain injury. METHODS: A systematic review and meta-analysis were performed following PRISMA guidelines. This review involved studies conducted in humans covering glycemic control in traumatic brain injury. A systematic literature search was performed in PubMed, Embase, EBSCO Host, Scopus, ScienceDirect, Medline, and LILACS from database inception to October 2020. The risk of bias was evaluated with the GRADE quality Scale. RESULTS: The results of this meta-analysis that involved 1236 patients included in 10 studies suggest that intensive glycemic control did not show significant differences in mortality compared with conservative management (RR 0.99 [95 % CI 0.81-1.21] p = 0.92). Intensive glycemic control reduced the risk of unfavorable clinical outcomes compared to standard management (RR 0.87 [95 % CI 0.78-0.96] p = 0.007) and increased favorable clinical outcomes compared to standard neurocritical care (RR 1.19 [95 % CI 1.02-138] p = 0.003). CONCLUSIONS: The possible effect of glycemic control could be associated with silent hypoglycemic episodes during intensive care. Further studies evaluating the impact of glycemic control in traumatic brain injury are necessary.

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Lesiones Traumáticas del Encéfalo , Control Glucémico , Hiperglucemia , Humanos , Lesiones Traumáticas del Encéfalo/terapia , Lesiones Traumáticas del Encéfalo/sangre , Glucemia/metabolismo

RESUMEN

Epidemiologic evidence has emerged showing an association between exposure to air pollution and increased risks of gestational diabetes mellitus (GDM). This study examines the effect of low-level air pollution exposure on a subclinical biomarker of hyperglycemia (i.e., HbA1c) in pregnant people without diabetes before conception. We measured HbA1c in 577 samples repeatedly collected from 224 pregnant people in Rochester, NY, and estimated residential concentrations of PM2.5 and NO2 using high-resolution spatiotemporal models. We observed a U-shaped trajectory of HbA1c during pregnancy with average HbA1c levels of 5.13 (±0.52), 4.97 (±0.54), and 5.43 (±0.40)% in early-, mid-, and late pregnancy, respectively. After adjustment for the U-shaped trajectory and classic GDM risk factors, each interquartile range increase in 10 week NO2 concentration (8.0 ppb) was associated with 0.09% (95% CI: 0.02 to 0.16%) and 0.18% (95% CI: 0.08 to 0.28%) increases in HbA1c over the entire pregnancy and in late pregnancy, respectively. These associations remained robust among participants without GDM. Using separate distributed lag models, we identified a period between 8th and 14th gestational weeks as critical windows responsible for increased levels of HbA1c measured at 14th, 22nd, and 30th gestational weeks. Our results suggest that low-level air pollution contributes to hyperglycemia in medically low-risk pregnant people.

Asunto(s)

Contaminación del Aire , Biomarcadores , Diabetes Gestacional , Hiperglucemia , Humanos , Embarazo , Femenino , Hiperglucemia/sangre , Adulto , Contaminantes Atmosféricos , Hemoglobina Glucada , Material Particulado , Exposición a Riesgos Ambientales

RESUMEN

The pathophysiological effects of chronic heavy metal exposures on human health remains uncertain. In this study, we developed a novel chronic, low-dose exposure of Cadmium (CLEC) model using the hepatocellular cell lines, HepG2 and HUH7. We modulated cell culture conditions to mimic human normoglycemic (5.6 mM) and hyperglycemic (15 mM) states with concomitant cadmium (Cd) exposures for 24 weeks. CLEC cells undergo non-trivial alterations in glucose signaling and metabolic characteristics within our model. We observe elevated baseline reactive oxygen species (ROS) production and decreased 2-NBDG uptake indicative of glucose metabolic dysfunction. Additionally, induction of metallothionein (MT) expression, increased activation of Akt signaling (via phosphorylation) and reduced IRS-2 protein expression are observed in CLEC cells. Cell line specific changes are observed with HepG2 showing a much higher MT gene induction compared to HUH7 cell line which impacts glucose metabolic dysfunction. Hyperglycemic culture conditions (representing type II diabetes) significantly modulate CLEC effects on cells. In conclusion, pathophysiologically relevant models of chronic heavy metal exposures are urgently needed to gain an in-depth, mechanistic understanding of the long-term impacts of toxic metals (e.g., Cd) on human metabolic health.

Asunto(s)

Cadmio , Hiperglucemia , Insulina , Transducción de Señal , Humanos , Transducción de Señal/efectos de los fármacos , Insulina/metabolismo , Hiperglucemia/inducido químicamente , Hiperglucemia/metabolismo , Cadmio/toxicidad , Células Hep G2 , Especies Reactivas de Oxígeno/metabolismo , Metalotioneína/metabolismo , Metalotioneína/genética , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Relación Dosis-Respuesta a Droga , Glucosa/metabolismo , Proteínas Sustrato del Receptor de Insulina/metabolismo , Proteínas Sustrato del Receptor de Insulina/genética

RESUMEN

To investigate the relationship between preoperative blood glucose levels and long-term all-cause mortality in patients with osteoporotic vertebral compression fractures (OVCF) who underwent percutaneous vertebroplasty (VP). This single-center retrospective study involved a chart review of patients admitted for VP to treat OVCF between 2013 and 2020. Patients with pathological or multiple fractures or those who did not undergo bone mineral density assessment were excluded. All relevant information was collected from electronic medical records. The survival status of all patients was confirmed at the end of March 2021. Cox proportional hazard models with multivariate adjustments were used to examine the effects of blood glucose levels on all-cause mortality. Overall, 131 patients were retrospectively analyzed (mean age: 75.8 ± 9.3 years, male patients: 26.7%) with a median follow-up period of 2.1 years. Preoperative hyperglycemia (hazard ratio: 2.668, 95% confidence interval [CI] 1.064, 6.689; p = 0.036) and glucose levels (hazard ratio: 1.007, 95% CI 1.002-1.012; p = 0.006) were found to be independently associated with a higher risk of all-cause mortality. This correlation remained significant even after adjusting for age and sex, and other factors and comorbidities that might affect outcomes (hazard ratio: 2.708, 95% CI 1.047, 7.003, p = 0.040 and 1.007; 95% CI 1.001, 1.013, p = 0.016, respectively). Furthermore, a history of diabetes mellitus was not a significant factor influencing long-term all-cause mortality. Preoperative glucose levels were found to be independently associated with survival outcomes in patients with OVCF who underwent VP. Conversely, diabetes mellitus was not associated with long-term all-cause mortality. Our findings highlight that preoperative hyperglycemia is a risk factor for long-term mortality in this aging surgical population.

Asunto(s)

Glucemia , Fracturas por Compresión , Fracturas Osteoporóticas , Fracturas de la Columna Vertebral , Vertebroplastia , Humanos , Masculino , Anciano , Femenino , Fracturas por Compresión/cirugía , Fracturas por Compresión/mortalidad , Fracturas Osteoporóticas/cirugía , Fracturas Osteoporóticas/mortalidad , Fracturas de la Columna Vertebral/mortalidad , Fracturas de la Columna Vertebral/cirugía , Fracturas de la Columna Vertebral/etiología , Glucemia/análisis , Glucemia/metabolismo , Estudios Retrospectivos , Anciano de 80 o más Años , Periodo Preoperatorio , Factores de Riesgo , Modelos de Riesgos Proporcionales , Hiperglucemia/mortalidad , Hiperglucemia/complicaciones , Hiperglucemia/etiología

RESUMEN

Objective: This study aims to investigate the pathogenesis of hyperglycemia and its associated vasculopathy using multiomics analyses in diabetes and impaired glucose tolerance, and validate the mechanism using the cell experiments. Methods: In this study, we conducted a comprehensive analysis of the metagenomic sequencing data of diabetes to explore the key genera related to its occurrence. Subsequently, participants diagnosed with impaired glucose tolerance (IGT), and healthy subjects, were recruited for fecal and blood sample collection. The dysbiosis of the gut microbiota (GM) and its associated metabolites were analyzed using 16S rDNA sequencing and liquid chromatograph mass spectrometry, respectively. The regulation of gene and protein expression was evaluated through mRNA sequencing and data-independent acquisition technology, respectively. The specific mechanism by which GM dysbiosis affects hyperglycemia and its related vasculopathy was investigated using real-time qPCR, Western blotting, and enzyme-linked immunosorbent assay techniques in HepG2 cells and neutrophils. Results: Based on the published data, the key alterable genera in the GM associated with diabetes were identified as Blautia, Lactobacillus, Bacteroides, Prevotella, Faecalibacterium, Bifidobacterium, Ruminococcus, Clostridium, and Lachnoclostridium. The related metabolic pathways were identified as cholate degradation and L-histidine biosynthesis. Noteworthy, Blautia and Faecalibacterium displayed similar alterations in patients with IGT compared to those observed in patients with diabetes, and the GM metabolites, tauroursodeoxycholic acid (TUDCA) and carnosine (CARN, a downstream metabolite of histidine and alanine) were both found to be decreased, which in turn regulated the expression of proteins in plasma and mRNAs in neutrophils. Subsequent experiments focused on insulin-like growth factor-binding protein 3 and interleukin-6 due to their impact on blood glucose regulation and associated vascular inflammation. Both proteins were found to be suppressed by TUDCA and CARN in HepG2 cells and neutrophils. Conclusion: Dysbiosis of the GM occurred throughout the entire progression from IGT to diabetes, characterized by an increase in Blautia and a decrease in Faecalibacterium, leading to reduced levels of TUDCA and CARN, which alleviated their inhibition on the expression of insulin-like growth factor-binding protein 3 and interleukin-6, contributing to the development of hyperglycemia and associated vasculopathy.

Asunto(s)

Carnosina , Disbiosis , Heces , Microbioma Gastrointestinal , Humanos , Disbiosis/microbiología , Carnosina/metabolismo , Masculino , Heces/microbiología , Intolerancia a la Glucosa/metabolismo , Inflamación/metabolismo , Células Hep G2 , Metagenómica , Femenino , Persona de Mediana Edad , Ácido Tauroquenodesoxicólico/metabolismo , Ácido Tauroquenodesoxicólico/farmacología , Hiperglucemia/metabolismo , Neutrófilos/metabolismo , ARN Ribosómico 16S/genética , Bacterias/clasificación , Bacterias/metabolismo , Bacterias/genética