Acute Hyperglycemia Research Articles

A Mouse Model of Hemorrhagic Transformation Induced by Acute Hyperglycemia Combined with Transient Focal Ischemia

A Mouse Model of Hemorrhagic Transformation Induced by Acute Hyperglycemia Combined with Transient Focal Ischemia

Acute hyperglycemia exacerbates neuroinflammation and cognitive impairment in sepsis-associated encephalopathy by mediating the ChREBP/HIF-1α pathway.

Delirium is a prominent symptom of sepsis-associated encephalopathy (SAE) and is highly prevalent in septic patients hospitalized in the intensive care unit, being closely connected with raised mortality rates. Acute hyperglycemia (AH) has been recognized as a separate risk factor for delirium and a worse prognosis in critically sick patients. Nevertheless, the exact contribution of AH to the advancement of SAE is still unknown. This research retrospectively evaluated the connection between blood glucose levels (BGLs) and the incidence of delirium and death rates in septic patients in the ICU of a tertiary comprehensive hospital. In addition, a septic rat model was induced through cecal ligation and puncture (CLP), after which continuous glucose infusion was promptly initiated via a central venous catheter post-surgery to evaluate the potential implications of AH on SAE. Next, septic rats were assigned to four groups based on target BGLs: high glucose group (HG, ≥ 300mg/dL), moderate glucose group (MG, 200-300mg/dL), normal glucose group (NG, < 200mg/dL), and a high glucose insulin-treated group (HI, 200-300mg/dL) receiving recombinant human insulin treatment (0.1IU/kg/min). The sham group (SG) received an equivalent volume of saline infusion and denoted the NG group. The effects of AH on neuroinflammation and cognitive function in septic rats were evaluated using behavioral tests, histopathological examination, TUNEL staining, ELISA, and Western blot. The effects of glucose levels on microglial activation and glucose metabolism following lipopolysaccharide (LPS, 1μg/mL) exposure were assessed using CCK8 assay, qRT-PCR, Western blot, and ELISA. Our findings revealed that AH during sepsis was a separate risk factor for delirium and assisted in predicting delirium occurrence. AH raised the levels of systemic and central inflammatory cytokines in septic rats, promoting neuronal apoptosis, blood-brain barrier disruption, and cognitive impairment. In addition, both in vivo and in vitro, an elevated glucose challenge increased the ChREBP, HIF-1α, glycolytic enzymes, and inflammatory cytokines expressions in microglia after exposure to CLP or LPS. These results collectively suggest that hyperglycemia can exacerbate neuroinflammation and delirium by enhancing microglial glycolysis under septic conditions, potentially mediated by upregulation of the ChREBP/HIF-1α signaling pathway.

Abstract 4134825: Diabetic ketoacidosis and hyperglycemic hyperosmolar state outcomes in diabetes patients hospitalized with ST-elevation myocardial infarction

Background: Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar state (HHS) are acute life-threatening hyperglycemia conditions. Aims: We aimed to assess their impact on type 2 diabetes patients admitted for ST-elevation myocardial infarction (STEMI). Methods: Data was extracted from the National Readmission Database (2016-2019). The primary endpoint was in-hospital mortality. Secondary endpoints included in-hospital arrhythmias, cardiogenic shock, and 30-day readmission and mortality. Results: A total of 112,829 patients hospitalized for STEMI with a concomitant diagnosis of type 2 diabetes were hospitalized between 2016 and 2019, of whom 112,799 were included in our analysis after the exclusion of patients with missing data ( Figure 1 ). Of those patients, 330 had a diagnosis of DKA, and 292 had a diagnosis of HHS. After 30 days from the initial hospitalization, 118 (35.7%) out of the initial DKA group, 102 (34.9%) out of the initial HHS group, and 26,523 (23.6%) of STEMI patients with diabetes were readmitted. The presence of DKA increased the odds of in-hospital mortality and cardiogenic shock by almost 2-fold (aOR = 2.30 [1.70-3.12], 2.055 [1.602-2.637], respectively) and renal failure by almost 5-fold (aOR = 5.175 [4.090-6.546]) ( Table 1 ). HHS was also associated with higher odds of mortality, acute renal failure, and cardiogenic shock. Within 30 days of initial admission, DKA and HHS increased the risk of readmission (aOR= 1.815 [1.449-2.75], 1.751 [1.376 - 2.228], respectively), but not mortality. Cardiovascular disease was the most common etiology of readmission in all patients ( Figure 2) . The prevalence of non-STEMI was the highest in DKA patients (22.9%), and the prevalence of STEMI was the highest in the HHS group (37.9%). Conclusion: The presence of diabetic ketoacidosis or hyperglycemic hyperosmolar states is associated with higher odds of mortality, renal failure, cardiogenic shock, and 30-day readmission in STEMI patients with type 2 diabetes.

The prognostic significance of stress hyperglycemia ratio for all-cause and cardiovascular mortality in metabolic syndrome patients: prospective cohort study.

The stress hyperglycemia ratio (SHR) is a new biomarker indicating acute hyperglycemia and predicting adverse outcomes in different conditions. Yet, its impact on metabolic syndrome (MetS) has not been studied. We explored the link between SHR and long-term all-cause and cardiovascular disease (CVD) mortality in MetS patients. We conducted a large prospective cohort study involving 9438 participants diagnosed with MetS, drawn from the 1999-2018 NHANES. MetS diagnosis was based on NCEP-ATPIII criteria. Participants were categorized into three groups based on SHR tertiles: T1 (SHR ≤ 0.890), T2 (SHR 0.890-0.992), and T3 (SHR ≥ 0.992). Cox regression and Kaplan-Meier curve analyses assessed the correlation between SHR and mortalities. Non-linear correlations were explored using restricted cubic splines, and stratification analysis was performed. Out of 9438 MetS patients, 1929 deaths occurred during an average follow-up of 107 ± 64 months, including 541 CVD deaths. All-cause and CVD mortality rates were significantly higher with elevated SHR values (T3) than lower tertiles (23.4% vs. 19.5% and 18.3%, P < 0.001; 6.8% vs. 5.3% and 5.1%, P = 0.007, respectively). A U-shaped relationship was observed between SHR and all-cause and CVD mortality (all P for non-linear < 0.001). Kaplan-Meier analysis indicated higher SHR values associated with increased risk of all-cause and CVD mortality (all log-rank P < 0.001). After adjusting for confounders, multivariate Cox regression showed SHR remained associated with a 1.256-fold and 1.023-fold risk of all-cause and CVD mortality. SHR independently correlates with all-cause and CVD mortality in MetS patients, displaying a U-shaped relationship with clinical endpoints.

The prognostic impact of stress hyperglycemia ratio for all-cause mortality in patients with Psoriasis.

Aims The stress hyperglycemia ratio (SHR) is a valuable biomarker of acute hyperglycemia, significantly correlated with unfavorable prognosis in various conditions. However, its impact on Psoriasis has not been studied. We explored the association between SHR and long-term mortality in psoriasis patients. Methods We conducted a prospective cohort study with 288 psoriasis patients from the 2003-2006 and 2009-2014 NHANES. Participants were divided into three groups based on SHR tertiles: T1 (SHR ≤ 0.870), T2 (SHR 0.870-0.958), and T3 (SHR ≥ 0.958). Cox regression and Kaplan-Meier analyses assessed the correlation between SHR and mortality, while restricted cubic splines explored non-linear correlations. ROC analyses determined the optimal SHR cut-off value for predicting clinical outcomes. Results Out of 288 Psoriasis patients, 38 all-cause deaths occurred during an average follow-up of 112.13 ± 45.154 months. Kaplan-Meier analysis indicated that higher SHR values were linked to an increased risk of all-cause mortality (log-rank P = 0.049). A U-shaped relationship was observed between SHR and all-cause mortality (P for non-linear = 0.028). Spearman correlation revealed significant associations between SHR and WC, BMI, neutrophil, monocyte, lymphocyte counts, SCr, uric acid, DM and MetS (all P < 0.05). After adjusting for confounders, multivariate Cox regression showed that SHR was associated with a 10.937-fold risk of all-cause mortality. ROC curve analysis identified an optimal SHR cut-off value of 1.045 for predicting long-term all-cause mortality in psoriasis patients. Conclusions Elevated SHR value independently correlates with all-cause mortality in Psoriasis patients, displaying a U-shaped relationship with clinical endpoints. An optimal SHR cut-off value of 1.045 has been determined for predicting clinical outcomes.

12553 Severe Hyperglycemia After Initiation Of Bictegravir Antiretroviral Therapy With Resolution Upon Discontinuation

Abstract Disclosure: S. Hudson: None. J. Aurora: None. K. Grossman: None. L. Kogelman: None. A.G. Pittas: None. Background: Antiretroviral therapy (ART) containing bictegravir (BIC), a second-generation integrase strand transfer inhibitor (INSTI), is a first-line treatment for HIV. There are mixed reports of INSTIs causing adverse metabolic effects, such as weight gain and hyperglycemia. There are cases of BIC causing hyperglycemia and diabetic ketoacidosis (DKA) within weeks to months following initiation; however, this has not been reported in clinical trials (1). It is unclear whether discontinuing BIC resolves hyperglycemia. We report a case of a patient with prediabetes who developed severe hyperglycemia after switching to a BIC-containing ART. The discontinuation of BIC resulted in significant improvement in glycemia, leading to the de-escalation of diabetes pharmacotherapy. Clinical Case: A 36-year-old woman with obesity was diagnosed with HIV during pregnancy, which was complicated by gestational diabetes mellitus. After pregnancy, she had prediabetes. Her initial ART was darunavir/cobicistat/emtricitabine/tenofovir alafenamide. Due to intolerable GI side effects, six years later, she was switched to bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF). Laboratory tests four months before starting BIC/FTC/TAF were consistent with prediabetes (HbA1c 6.4%, non-fasting blood glucose of 118 mg/dL). After one month, she was started on metformin when her HbA1c increased to 9.1% with a non-fasting blood glucose of 332 mg/dL. Another month later, HbA1c increased to 12.8% with a non-fasting blood glucose of 685 mg/dL without DKA. She was hospitalized for diabetes management. There were no significant changes in weight, viral load, or CD4 count. A search for secondary causes of hyperglycemia (diabetogenic medications, hypercortisolism, and autoimmune diabetes) was not revealing. She was discharged on metformin and insulin glargine. Her HIV regimen was switched to FTC/TAF and doravirine due to suspicion of BIC-induced hyperglycemia. After five months, she developed symptoms of hypoglycemia, and her estimated HbA1c by continuous glucose monitoring was 6.3%. Insulin glargine was discontinued. While on metformin, HbA1c three months later was 6.3%. Two years later on metformin and linagliptin: HbA1c was 6.1% and beta-cell function did not reveal insulin deficiency or resistance (non-fasting blood glucose 96 mg/dL, insulin 13.5 uIU/mL [RR 2.6-24.9 mIU/mL], C-peptide 3.7 ng/mL [RR 1.1-4.4 ng/mL]). Conclusion: Patients with HIV and a history of obesity and/or dysglycemia who are switched to a BIC-containing ART regimen should be educated and monitored for acute hyperglycemia. This may be due to impaired beta-cell function and/or insulin resistance; however, further research is needed to understand the mechanism. An alternative ART regimen should be considered if hyperglycemia develops. Reference: 1. Nolan NS, et al. Open Forum Infect Dis. 2021;16;8(5): ofab077. Presentation: 6/3/2024

Integrating diabetes care into an oncology practice: A patient-centric model of care delivery at a safety-net health system.

2 Background: Oncologic treatments can disrupt glycemic control in people with diabetes and induce dysglycemia in individuals without diabetes through the use of steroids and/or targeted therapies. Severe hyperglycemia can result in delay/interruption of oncologic care and emergency department (ED) utilization. Here we report on an integrated model of diabetes care at a safety-net system, where patients commonly use the ED for their care. Methods: Parkland Health is an academic-affiliated safety-net system, primarily providing care for the un-/under-insured patients in Dallas County. An advanced nurse practitioner specializing in diabetes care (DM-ANP), supervised by an endocrinologist, was embedded in oncology clinics. Patients were referred to the DM-ANP by their oncology provider, or through an automated process if they had a recent hemoglobin A1c &gt;8.0% or a random blood sugar &gt; 250mg/dL. Patient education was provided by a trained nurse educator. Nutrition consult was available through an oncology dietitian. An acute hyperglycemia management protocol was developed to manage patients in the infusion center and prevent unnecessary ED visits. Results: Between March 2021 and March of 2024, the DM-ANP provided 4,276 visits to 797 distinct patients (average, 1425 visits per year). Breast cancer was the most common malignancy among patients seen in the integrated clinic. DM-ANP visits were coupled with oncology visits (clinic or infusion) or via telehealth, thereby increasing access and decreasing number of days patients had to come to clinic to receive care. Telehealth visit rate was highest in 2021 (27.5%) reflecting the impact of the pandemic, and subsequently dropped to 10.1% in 2023. Patients who were seen by the DM-ANP had an overall lower number of ED visits. Comparing prior vs post establishing care with the DM-ANP, the total number of ED visits by patients with diabetes significantly reduced in 2021-2022 (2021: 970 vs. 241, p &lt;0.01; 2022: 796 vs. 501, p&lt;0.01) before equilibrating in 2023-2024; (2023: 426 vs. 468, p=0.24). On average, patients had 1.2 less ED visits after receiving care from the DM-ANP. Since in-person visits were coupled with other oncology visits, the no-show rate for DM-ANP mirrored the rates for oncology clinics/infusion visits. Conclusions: Integrating diabetes/glycemic management into our oncology practice provided a patient-centric model of care delivery, improved visit adherence compared to an off-site model, reduced the time-toxicity by having fewer clinic visit days. Future directions include comparing oncologic outcomes in patients who had DM-ANP management to those who were managed by primary care.

Altered oxidant and antioxidant levels are associated with vascular stiffness and diabetic kidney disease in type 1 diabetes after exposure to acute and chronic hyperglycemia

BackgroundHyperglycemia-induced oxidative stress is a well-established pathological mediator of vascular complications in diabetes. We assessed plasma oxidant and antioxidant levels in response to acute and chronic hyperglycemia in relation to vascular stiffness and varying degrees of kidney disease in type 1 diabetes individuals.MethodsThe acute hyperglycemia study included 22 type 1 diabetic individuals with normal albumin excretion rate (AER) and 13 non-diabetic controls. These individuals received an acute glucose challenge during a 120-minute hyperglycemic clamp. The chronic hyperglycemia study included 118 type 1 diabetic individuals with chronically low (n = 60) or high (n = 58) HbA1c concentrations and varying degrees of diabetic kidney disease (DKD) classified as normal, moderate, or severe albuminuria (AER). Levels of malondialdehyde (MDA), reactive oxygen metabolites (ROMs), total antioxidant capacity (TAC), biological antioxidant potential (BAP) and superoxide dismutase (SOD) were measured from plasma or serum samples in the FinnDiane study.ResultsLevels of MDA (p < 0.01) and ROMs (p < 0.01) were elevated in type 1 diabetes individuals compared to non-diabetic controls at baseline. Acute hyperglycemia further increased MDA levels (p < 0.05) and sustained the elevation of ROMs in type 1 diabetes individuals. Acute hyperglycemic challenge impaired TAC in both non-diabetic (p < 0.05) and type 1 diabetes (p < 0.01) individuals compared to baseline whereas BAP was increased (p < 0.05) with no difference observed in non-diabetic controls. There was a positive association between high circulating MDA and AIx (r2 = 0.611, p = 0.05), and between delta ROMs and delta AIx (r2 = 0.955, p = 0.014) in combined analysis of individuals with type 1 diabetes and non-diabetic controls. Type 1 diabetes individuals with varying status of DKD, showed elevated levels of ROMs in those with high HbA1c compared to their counterpart with low HbA1c (p < 0.05). Individuals with severe albuminuria showed elevated ROM levels (p < 0.01) and depressed antioxidant capacity (p < 0.01) compared to those with normal AER of comparable HbA1c concentrations.ConclusionsBiomarkers of oxidative stress are associated with vascular stiffness and DKD following acute and chronic hyperglycemic exposure and may provide added value to HbA1c in understanding disease pathology, predicting risk and assessing the status of secondary complications of type 1 diabetes.

Hyperglycemia selectively increases cerebral non-oxidative glucose consumption without affecting blood flow.

Multiple studies have shown that hyperglycemia increases the cerebral metabolic rate of glucose (CMRglc) in subcortical white matter. This observation remains unexplained. Using positron emission tomography (PET) and euinsulinaemic glucose clamps, we found, for the first time, that acute hyperglycemia increases non-oxidative CMRglc (i.e., aerobic glycolysis (AG)) in subcortical white mater as well as in medial temporal lobe structures, cerebellum and brainstem, all areas with low euglycemic CMRglc. Surprisingly, hyperglycemia did not change regional cerebral blood flow (CBF), the cerebral metabolic rate of oxygen (CMRO2), or the blood-oxygen-level-dependent (BOLD) response. Regional gene expression data reveal that brain regions where CMRglc increased have greater expression of hexokinase 2 (HK2). Simulations of glucose transport revealed that, unlike hexokinase 1, HK2 is not saturated at euglycemia, thus accommodating increased AG during hyperglycemia.

Diagnosis of acute hyperglycemia based on data-driven prediction models

Acute hyperglycemia is a common endocrine and metabolic disorder that seriously threatens the health and life of patients. Exploring effective diagnostic methods and treatment strategies for acute hyperglycemia to improve treatment quality and patient satisfaction is currently one of the hotspots and difficulties in medical research. This article introduced a method for diagnosing acute hyperglycemia based on data-driven prediction models. In the experiment, clinical data from 1000 patients with acute hyperglycemia were collected. Through data cleaning and feature engineering, 10 features related to acute hyperglycemia were selected, including BMI (Body Mass Index), TG (triacylglycerol), HDL-C (High-density lipoprotein cholesterol), etc. The support vector machine (SVM) model was used for training and testing. The experimental results showed that the SVM model can effectively predict the occurrence of acute hyperglycemia, with an average accuracy of 96 %, a recall rate of 84 %, and an F1 value of 89 %. The diagnostic method for acute hyperglycemia based on data-driven prediction models has a certain reference value, which can be used as a clinical auxiliary diagnostic tool to improve the early diagnosis and treatment success rate of acute hyperglycemia patients.

Hyperglycemia induced cathepsin L maturation linked to diabetic comorbidities and COVID-19 mortality.

Diabetes, a prevalent chronic condition, significantly increases the risk of mortality from COVID-19, yet the underlying mechanisms remain elusive. Emerging evidence implicates Cathepsin L (CTSL) in diabetic complications, including nephropathy and retinopathy. Our previous research identified CTSL as a pivotal protease promoting SARS-CoV-2 infection. Here, we demonstrate elevated blood CTSL levels in individuals with diabetes, facilitating SARS-CoV-2 infection. Chronic hyperglycemia correlates positively with CTSL concentration and activity in diabetic patients, while acute hyperglycemia augments CTSL activity in healthy individuals. In vitro studies reveal high glucose, but not insulin, promotes SARS-CoV-2 infection in wild-type cells, with CTSL knockout cells displaying reduced susceptibility. Utilizing lung tissue samples from diabetic and non-diabetic patients, alongside Leprdb/dbmice and Leprdb/+mice, we illustrate increased CTSL activity in both humans and mice under diabetic conditions. Mechanistically, high glucose levels promote CTSL maturation and translocation from the endoplasmic reticulum (ER) to the lysosome via the ER-Golgi-lysosome axis. Our findings underscore the pivotal role of hyperglycemia-induced CTSL maturation in diabetic comorbidities and complications.

Hyperglycemia induced cathepsin L maturation linked to diabetic comorbidities and COVID-19 mortality

Diabetes, a prevalent chronic condition, significantly increases the risk of mortality from COVID-19, yet the underlying mechanisms remain elusive. Emerging evidence implicates Cathepsin L (CTSL) in diabetic complications, including nephropathy and retinopathy. Our previous research identified CTSL as a pivotal protease promoting SARS-CoV-2 infection. Here, we demonstrate elevated blood CTSL levels in individuals with diabetes, facilitating SARS-CoV-2 infection. Chronic hyperglycemia correlates positively with CTSL concentration and activity in diabetic patients, while acute hyperglycemia augments CTSL activity in healthy individuals. In vitro studies reveal high glucose, but not insulin, promotes SARS-CoV-2 infection in wild-type cells, with CTSL knockout cells displaying reduced susceptibility. Utilizing lung tissue samples from diabetic and non-diabetic patients, alongside Leprdb/dbmice and Leprdb/+mice, we illustrate increased CTSL activity in both humans and mice under diabetic conditions. Mechanistically, high glucose levels promote CTSL maturation and translocation from the endoplasmic reticulum (ER) to the lysosome via the ER-Golgi-lysosome axis. Our findings underscore the pivotal role of hyperglycemia-induced CTSL maturation in diabetic comorbidities and complications.

Relationship between hyperglycemia and intraocular pressure, corneal biomechanics, and corneal topography during the oral glucose tolerance test in nondiabetic patients.

Altered corneal biomechanics in patients with diabetes may affect intraocular pressure (IOP) measurements. Although a relationship between IOP and glucose levels has been reported in diabetic and nondiabetic patients, the mechanism by which hyperglycemia influences IOP is unclear. The aim of this study was to determine the effects of hyperglycemia on IOP, corneal biomechanics, and anterior segment parameters during the oral glucose tolerance test (OGTT) in nondiabetic patients. Twenty-one patients without DM who underwent OGTT were included in this study. A complete ophthalmologic examination was performed before the test. Blood glucose, insulin level, IOP (iCare rebound tonometer), Ocular Response Analyzer, and corneal topography (Pentacam) measurements were obtained at 0, 1, and 2h during the OGTT. Data from the patients' right eyes were included in the analysis. The mean age of the patients was 46.9 ± 11.0years. There was a statistically significant difference in IOP between 1 and 2h (p = 0.03) and a clinically significant difference between 0 and 1h (p = 0.06). Corneal resistance factor was lower at 2h than 1h (p = 0.03), while central cornea thickness was increased at 1h (p = 0.01) and 2h (p = 0.05) compared to 0h. There was positive partial correlation between hyperglycemia and IOP at 1h (p = 0.049, r = 0.67). The positive partial correlation between IOP and glucose level suggests that acute hyperglycemia may lead to increased IOP. However, further research is needed to explain the mechanism of IOP elevation in the hyperglycemic phase during OGTT.

Acute Hyperglycemia and Its Impact on Mortality of Acute Coronary Syndrome Patients: A Systematic Review.

Acute hyperglycemia or stress hyperglycemia is a frequent finding in patients with acute coronary syndrome (ACS). Several studies have demonstrated the association between acute hyperglycemia with short- and long-term mortality in ACS patients.But the evidence is not concrete. We gathered 1056 articles from three databases, i.e., PubMed, Google Scholar, and Science Direct using different search strategies and filters. We then removed duplicates and 919 articles were screened with title abstract and full text. After a full-text screening of 169 articles, we removed 116 articles. We then applied eligibility criteria and did a quality assessment of articles and finally, we included 21 articles in our study. The 21 articles spanned years 2014 to 2024. Of them, 16 articles were observational studies, two were systematic reviews and meta-analyses, and three were review articles. Six articles used stress hyperglycemia ratio (SHR) alone, seven articles used admission blood glucose (ABG) alone, two used fasting plasma glucose (FPG) alone and one used SHR, ABG, and FPG together as a parameter to measure acute hyperglycemia. Short-term poor outcomes (in-hospital, <30 days) were studied in 12 studies, and long-term poor outcomes (>30 days-1 year, >1 year) were studied in six studies. A positive correlation between acute hyperglycemia and short- and long-termmortality was found in our 21 included studies. The three parameters which are used to quantify acute or stress hyperglycemia in our study, i.e., SHR, ABG, andFPG predict both short- and long-term mortality in ACS patients. Further study is needed to determine the accurate cutoff level of hyperglycemia to be called acute hyperglycemia in diabetics.We tried to review the recent literature on this topic to deepen our understanding of this topic and to provide a base for future research.

Okra (Abelmoschus esculentus L. moench) fruit powder standardized in flavonoids improves glycemic control and metabolic memory in acute and chronic hyperglycemia

Type 2 diabetes mellitus (T2DM) is a chronic disease with high global prevalence characterized by persistent hyperglycemia. Elevated blood glucose levels are associated with constant oxidative stress and increased protein glycation, establishing a metabolic memory state. Therefore, the efficacy of the Okra (Abelmoschus esculentus L. moench) Fruit Powder Standardized in Flavonoids (OFP-SF) was evaluated in glucose homeostasis, oxidative stress, and metabolic memory, using zebrafish models of acute and chronic hyperglycemia. The OFP-SF was produced from dried fresh fruits and subsequently subjected to characterization regarding its antioxidant potential and chemical composition. Finally, the product was standardized to contain 1.6% flavonoids. In acute hyperglycemia, OFP-SF at doses of 125 μg and 250 μg demonstrated the ability to normalize blood glucose levels, reaching levels of 94.56 ± 5.9 mg/dL and 76.88 ± 8.9 mg/dL, respectively, when administered prior to glucose overload. The same doses were tested in a chronic hyperglycemia model, where after a seven-day treatment, animals receiving 125 and 250 μg of OFP-SF exhibited glycemic values of 73.45 ± 15.67 mg/dL and 33.96 ± 5.31 mg/dL, respectively, comparable to those observed in the Control group (49.48 ± 2.77 mg/dL). Furthermore, OFP-SF was able to mitigate metabolic memory by reducing oxidative stress and protein glycation in the brain, liver, and eye tissues of hyperglycemic zebrafish. These findings provide a basis for developing new products that utilize the phytochemical potential of A. esculentus fruits for the prevention and adjunctive treatment of T2DM.

Acute Hyperglycemia-Induced Injury in Myocardial Infarction.

Acute hyperglycemia is a transient increase in plasma glucose level (PGL) frequently observed in patients with ST-elevation myocardial infarction (STEMI). The aim of this review is to clarify the molecular mechanisms whereby acute hyperglycemia impacts coronary flow and myocardial perfusion in patients with acute myocardial infarction (AMI) and to discuss the consequent clinical and prognostic implications. We conducted a comprehensive literature review on the molecular causes of myocardial damage driven by acute hyperglycemia in the context of AMI. The negative impact of high PGL on admission recognizes a multifactorial etiology involving endothelial function, oxidative stress, production of leukocyte adhesion molecules, platelet aggregation, and activation of the coagulation cascade. The current evidence suggests that all these pathophysiological mechanisms compromise myocardial perfusion as a whole and not only in the culprit coronary artery. Acute hyperglycemia on admission, regardless of whether or not in the context of a diabetes mellitus history, could be, thus, identified as a predictor of worse myocardial reperfusion and poorer prognosis in patients with AMI. In order to reduce hyperglycemia-related complications, it seems rational to pursue in these patients an adequate and quick control of PGL, despite the best pharmacological treatment for acute hyperglycemia still remaining a matter of debate.

Plant-derived compounds normalize platelet bioenergetics and function in hyperglycemia

BackgroundPolyphenols have been shown to decrease oxidative stress and modulate glycemic response. Nevertheless, their effect on platelet bioenergetics and clot structure in diabetes and hyperglycemia is unknown. ObjectivesTo investigate the effect of polyphenols on human platelet bioenergetics and its subsequent effect on clot structure in normoglycemia vs acute hyperglycemia in vitro. MethodsFour polyphenols (resveratrol, hesperetin, epigallocatechin gallate [EGCG], and quercetin) were selected for initial analysis. Healthy volunteers’ isolated platelets/platelet-rich plasma were treated with 5 or 25 mM glucose to represent normoglycemia and acute hyperglycemia, respectively. Platelet-derived reactive oxygen species (ROS), citrate synthase activity (mitochondrial density), mitochondrial calcium flux, and mitochondrial respiration were performed following exposure to polyphenols (20 µM, 1 hour) to determine their effects on platelet bioenergetics. Procoagulant platelets (annexin V) and fibrin fiber density (Alexa Fluor-488 fibrinogen; Invitrogen) were analyzed by laser scanning confocal microscopy, while clot porosity was determined using platelet-rich plasma following exposure to polyphenols (20 µM, 20 minutes). ResultsAcute hyperglycemia increased ROS, mitochondrial calcium flux, maximal respiration, and procoagulant platelet number. Resveratrol, quercetin, and EGCG reduced platelet ROS in normoglycemic and acute hyperglycemic conditions. Mitochondrial density was decreased by quercetin and EGCG in normoglycemia. Resveratrol and EGCG reduced mitochondrial calcium flux in acute hyperglycemia. Resveratrol also decreased procoagulant platelet number and attenuated oxygen consumption rate in normoglycemia and acute hyperglycemia. No effect of hyperglycemia or polyphenols was observed on fibrin fiber density or clot pore size. ConclusionOur results suggest polyphenols attenuate increased platelet activity stemming from hyperglycemia and may benefit thrombosis-preventative strategies in patients with diabetes.

Fructosamine in llamas (Lama glama) is associated with sex, body condition score, and hematologic and serum parameters.

The objective of this study was to provide orientation values for fructosamine in adult llamas and to characterize relationships with other laboratory and clinical parameters. Data from 22 healthy adult llamas of both sexes. A retrospective study was conducted with the findings of a veterinary herd visit from August 2022. Fructosamine measured from plasma samples was characterized, and its relationships with clinical and laboratory diagnostic data was analyzed using descriptive statistics and correlation analysis. Fructosamine was 311 ± 34 µmol/L (mean ± SD), with a range of 254.8 to 409.2 µmol/L. Males showed significantly higher plasma fructosamine levels than females (P < .05). Plasma fructosamine revealed significant positive correlations with glucose, total protein, and albumin and also with PCV, hemoglobin, calcium, sodium, and selenium. Female llamas revealed further positive correlations with body condition scoring. The results of this study can be used as orientation values for fructosamine in llamas. Fructosamine is used to distinguish acute hyperglycemia caused by stress from chronic hyperglycemia in other species, which might be caused by disorders of the glucose metabolism.

Stress, Hyperglycemia, and Insulin Resistance Correlate With Neutrophil Activity and Impact Acute Myocardial Infarction Outcomes.

Introduction Acute insulin resistance (IR) and hyperglycemia are frequently observed during acute myocardial infarction (AMI), significantly influencing both immediate and long-term patient outcomes, irrespective of diabetic status. Neutrophilia and increased neutrophil activity, which are common in these scenarios, have been associated with poorer prognoses, as demonstrated in our recent findings. While it is well established that neutrophils and stress-induced hyperglycemia exacerbate inflammation and hinder recovery, the complex interplay between these factors and their combined impact on AMI prognosis remains inadequately understood. This study aims to investigate the effects of stress hyperglycemia and IR on AMI patients at the onset of the event and to elucidate the relationship between these metabolic disturbances and inflammatory markers, particularly neutrophils. Methods We conducted a longitudinal prospective study on 219 AMI patients at Elias Emergency Hospital in Bucharest, Romania, from April 2021 to September 2022. Patients were included within 24 hours of AMI with ST-segment elevation and excluded if they had acute infections or chronic inflammatory diseases. Blood samples were collected to study inflammatory biomarkers, including neutrophil extracellular traps (NETs), S100A8/A9, interleukin (IL)-1β, IL-18, and IL-6. Diabetic and pre-diabetic statuses were defined using glycated hemoglobin (HbA1c) and medical history (ADA 2019 criteria). To assess glycemic parameters, we employed the glycemia ratio (GR) and the homeostatic model assessment of insulin resistance (HOMA-IR) index, enabling a precise evaluation of stress hyperglycemia, acute IR, and their prognostic implications. Patients were stratified into groups based on GR calculations, categorized as under-average glycemia, normal glycemia, and stress hyperglycemia. Results The majority of patients in the stress hyperglycemia group exhibited an unfavorable prognosis. This group also demonstrated significantly elevated neutrophil counts and neutrophil-to-lymphocyte ratios (NLR). The GR was significantly and positively correlated with inflammation markers, including neutrophil count (Pearson's R = 0.181, P = 0.008) and NLR (Pearson's R = 0.318, P < 0.001), but showed no significant correlation with other evaluated inflammatory markers. Conclusions Our findings suggest that poor outcomes in AMI patients may be associated with stress hyperglycemia, as indicated by GR. AcuteIR, quantified by GR and HOMA-IR, exhibits a strong correlation with neutrophil count and NLR within the first 24 hours of AMI onset. However, no significant correlation was observed with other inflammatory markers, such as IL-1β, IL-18, and IL-6, underscoring the specific interplay between IR and neutrophil activity in this setting.

Perioperative Short-Term Glucocorticoids Do Not Increase Incidence of Complications after Total Joint Arthroplasty in Patients with Rheumatoid Arthritis.

The safety and analgesic efficacy of perioperative glucocorticoids have been established for patients without rheumatoid arthritis. Therefore, our study aims to investigate whether similar benefits can be observed in patients with rheumatoid arthritis undergoing total joint arthroplasty. Specifically, we aim to explore the impact of perioperative glucocorticoid use on postoperative complications, opioid consumption, incidence of hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission in this patient population. Approval for the study protocol was obtained from the Medical Research Ethics Committee at Sichuan University, aligning with the principles outlined in the Declaration of Helsinki. We retrospectively analyzed a consecutive series of patients with rheumatoid arthritis who underwent total joint arthroplasty at our medical center between November 2009 and April 2021 and who were not on chronic glucocorticoid therapy before surgery. Those who received glucocorticoids at any time during hospitalization were compared to those who did not in terms of acute complications within 90 days after surgery as well as postoperative rescue opioid consumption, hypotension, and hyperglycemia during hospitalization. The two groups were also compared in terms of overall duration of hospitalization, all-cause mortality within 30 days, and readmission for any reason within 90 days. Continuous data were assessed for significance using the independent-samples t test. Categorical data were assessed using the Pearson chi-squared test. Of the 849 patients included in the analysis, 598 administered perioperative glucocorticoids and 251 did not. Prior to surgery, the two groups did not differ significantly in any clinicodemographic variable that we examined. The incidence of acute postoperative complications (2.3% vs. 4.0%, p = 0.187) and acute postoperative infection (2.0% vs. 2.8%, p = 0.482) was comparable between those who received perioperative glucocorticoids and those who did not, but the former group exhibited a significantly lower incidence of rescue opioid use (17.9% vs. 44.6%, p < 0.001) as well as significantly lower total rescue opioid consumption (4.7 ± 2.1 mg vs. 8.9 ± 4.6 mg, p < 0.001). However, the two groups showed similar incidences of postoperative hypotension, hyperglycemia, 30-day mortality, and 90-day re-admission. Perioperative glucocorticoids may reduce the need for rescue opioids after total joint arthroplasty of rheumatoid arthritis patients, without increasing the incidence of acute complications, hypotension or hyperglycemia.