Hyperglycemic Group Research Articles

Maternal Glycemia and Its Pattern Associated with Offspring Neurobehavioral Development: A Chinese Birth Cohort Study

Background/Objectives: This study investigates the impact of maternal glycemic levels during early and late pregnancy on offspring neurodevelopment in China. Methods: Fasting plasma glucose (FPG) and triglyceride (TG) levels were measured in maternal blood during pregnancy, and the TyG index was calculated to assess insulin resistance. Hyperglycemia was defined as FPG > 5.1 mmol/L. Neurodevelopmental outcomes in offspring aged 6–36 months were evaluated using the China Developmental Scale for Children, focusing on developmental delay (DD) and developmental quotient (DQ). Mothers were categorized into four glycemic groups: healthy glycemia group (HGG), early pregnancy hyperglycemia group (EHG), late pregnancy hyperglycemia group (LHG), and full-term hyperglycemia group (FHG). Linear and logistic regression models were applied. Results: Among 1888 mother–child pairs, hyperglycemia and FPG were associated with an increased risk of overall DD (aOR = 1.68; 95% CI 1.07–2.64) and lower DQ (aBeta = −1.53; 95% CI −2.70 to −0.36). Elevated FPG was linked to DD in fine motor and social behaviors. Compared to HGG, LHG and FHG significantly increased the risk of overall DD (aOR = 2.18; 95% CI 1.26–3.77; aOR = 2.64; 95% CI 1.38–5.05), whereas EHG did not. Male offspring were particularly vulnerable to early pregnancy hyperglycemia (aBeta = −2.80; 95% CI −4.36 to −1.34; aOR = 2.05; 95% CI 1.10–3.80). Conclusions: Maternal glycemic levels during pregnancy influence offspring neurodevelopment, with persistent hyperglycemia significantly increasing DD risk. Early pregnancy hyperglycemia particularly affects male offspring, underscoring the need for glycemic management during pregnancy.

Investigating the inflammatory mechanism of notoginsenoside R1 in Diabetic nephropathy via ITGB8 based on network pharmacology and experimental validation

BackgroundDiabetes often causes diabetic nephropathy (DN), a serious long-term complication. It is characterized by chronic proteinuria, hypertension, and kidney function decline, can progress to end-stage renal disease, lowering patients’ quality of life and lifespan. Inflammation and apoptosis are key to DN development. Network pharmacology, clinical correlation, and basic experimental validation to find out how NGR1 might work to reduce inflammation in DN treatment. The study aims to improve DN treatment with new findings.MethodsTo determine how NGR1 treats DN, this study used network pharmacology, clinical correlation, and basic experimental validation. Three methods were used to predict NGR1 drug targets: ChEMBL, SuperPred, and Swiss Target Prediction. Drug targets are linked to diseases by molecular docking. A clinical correlation analysis using the Nephroseq Classic (V4) database looked at the strong link between medication targets and the development, progression, and renal function of DN. Additional research showed that NGR1 reduces high blood sugar-induced podocyte inflammation.ResultsThe integrin subunit beta 8 (ITGB8) protein is a potential NGR1 therapeutic target for DN. It may be linked to inflammatory proteins like caspase 3 and IL-18. Validation of the molecular docking showed that SER-407, ALA-22, Ala-343, and TYR-406 form hydrogen bonds with NGR1 and ITGB8. These interactions represent pharmacodynamic targets. Clinical correlation showed that DN patients had significantly lower ITGB8 expression levels than healthy individuals. Between 50 and 80 years old, DN patients’ ITGB8 expression levels decreased. ITGB8 expression was lowest in renal function conditions, with eGFR values of 15–29 ml/min/1.73 m2. In the db/db mouse model, downregulation of ITGB8 expression in renal tissue was associated with renal inflammatory damage. The hyperglycemic group had significantly lower levels of nephrin and caspase-3 protein, but higher levels of cleaved caspase-1 protein. Giving NGR1 in different amounts (1, 3, 10, and 30 µM) greatly decreased the expression of caspase3, stopped the expression of cleaved caspase1, and lowered the damage caused by NLRP3 in podocytes.ConclusionWe identified several NGR1 pharmacological targets and found that the ITGB8 protein is a key drug target linked to inflammation and DN. ITGB8 is critical for DN development and can help to reduce high blood sugar-induced podocyte inflammation.

Correlation of systemic immune inflammation and serum uric acid with gout: based on NHANES.

This study aimed to explore the relationship of systemic immune inflammation index (SII) and uric acid with gout using NHANES 2017-2018 data. Data were collected from the 2017-2018 circle of the NHANES database. SII was calculated based on the counts of lymphocytes (LC), neutrophils (NC), and platelets (PC). Data on gout patients were collected from questionnaires. Logistic regression analysis and subgroup analysis were used to explore the relationship between SII and gout. A total of 4517 participants were included in the study, with 273 individuals in the gout group and 4244 in the non-gout group. Logistic regression analysis showed that SII and serum uric acid were higher in the gout group than those in the non-gout group. SII ≥ 511.8 and uric acid ≥ 7.0mg/dL may be positively associated with gout. Further subgroup analysis revealed that the level of SII was positively associated with gout in the female group and the group with eGFR of 60-89.9mL/min/1.73 m2. Serum uric acid was positively associated with gout in the age, hypertension, hyperglycemia, and male groups and the group with eGFR ≥ 60mL/min/1.73 m2. There are positive correlations of SII and serum uric acid with gout. Our study suggests that SII could be a novel, valuable, and feasible inflammatory marker for gout. Key Points • Gout is a joint disease associated with hyperuricemia. The mechanism of the disease involves multiple complex factors, including metabolic disorders and inflammation. • Systemic immune inflammation index (Sll), as an evaluation index of systemic inflammatory responses, can reflect the body's inflammatory changes when the immune system is continuously activated with chronic inflammation of joints and other tissues. • We used the NHANES database to explore the relationship of SII and uric acid with gout, providing a basis for the diagnosis of gout and prognostic assessment of gout patients.

Correlation between admission hyperglycemia and postoperative pneumonia after hip fracture surgery: A propensity score-matched study

The association between admission hyperglycemia and postoperative pneumonia is unclear in hip fracture patients. We investigated the relationship between admission hyperglycemia and postoperative pneumonia after hip fracture surgery. This retrospective study analyzed data from 1,267 geriatric patients admitted for hip fractures. Patients were categorized into normoglycemic (< 6.10 mmol/L) and hyperglycemic (≥ 6.10 mmol/L) groups based on admission blood glucose levels. Multivariable logistic regression and propensity score matching (PSM) were used to control for potential confounding variables and estimate adjusted odds ratios and 95% confidence intervals for postoperative pneumonia (POP). We also examined the dose-dependent link between admission blood glucose and the likelihood of developing POP. Further analyses evaluated whether admission hyperglycemia has differing impacts on POP outcomes among hip fracture patients without diabetes (NDM) versus those with diabetes (DM). Additionally, subgroup analyses were conducted to assess the influence of other factors on the relationship between admission blood glucose and POP occurrence. Patients with admission hyperglycemia had significantly higher rates of POP compared to normoglycemic patients, both before (13.2% vs. 4.8%) and after (10.1% vs. 5.8%) PSM. Admission hyperglycemia is an independent risk factor of POP (OR = 2.64, 95% CI: 1.42–4.92, p = 0.002). The association persisted after PSM(OR = 2.90, 95% CI: 1.35–3.86, p = 0.016). Additionally, higher blood glucose levels correlated with a greater likelihood of developing POP. A dose–response relationship was observed between blood glucose levels and the risk of POP. Non-diabetic group patients with hyperglycemia were at higher risk of POP than diabetic group patients with hyperglycemia. Finally, the relationship between hyperglycemia and increased POP risk is modulated and influenced by the ASA classification of the patient. Admission hyperglycemia is an independent risk factor for POP after hip fracture surgery in the elderly. There is a dose–response relationship between admission blood glucose and the occurrence of POP, which is more significant in non-diabetic patients than diabetic patients.

Evaluating Hospital Revisit Risk in Patients Discharged from the Emergency Department with Blood Glucose of 300 mg/dL (16.7 mmol/L) or Greater

Background: In the emergency department (ED), hyperglycemia may be overlooked due to non-diabetes mellitus (DM) primary diagnoses. We compared the risk of all-cause hospital revisits within 30 days after ED discharge in DM patients with normal blood glucose (BG), moderate hyperglycemia, and severe hyperglycemia. Methods: This was a retrospective cohort study of patients 18 years and older discharged from a tertiary care ED between 1 January and 31 March 2018. The severe hyperglycemia group had BG levels of 300 mg/dL (16.7 mmol/L) or greater. The moderate hyperglycemia group had a history of DM, all BG levels less than 300 mg/dL (16.7 mmol/L), and at least one BG level of 180 mg/dL (10 mmol/L) or greater. The normal BG group had a history of DM and BG less than 180 mg/dL (10 mmol/L). Results: Of 302 patients who met criteria, 118 had severe hyperglycemia, 67 had moderate hyperglycemia, and 117 had normal BG. No significant difference between the severe hyperglycemia, moderate hyperglycemia, and normal BG groups was found in 30-day all-cause hospital revisits (19.5% vs. 10.4% vs. 15.4%, respectively, p = 0.25). Patients with a past medical history (PMH) of atherosclerotic cardiovascular disease (ASCVD) or any ED visit in the year preceding the index visit each had an increased risk of a hospital revisit within 30 days (p = 0.025) after covariate adjustment; the adjusted risk of a 30-day hospital revisit among those with a PMH of ASCVD was 2.68 times greater than the risk among those without a history of ASCVD (95% CI: 1.59 to 4.53), and the adjusted RR of a 30-day revisit among those who had an ED visit in the prior year was 1.92 times greater than those without an ED visit in the prior year (95% CI: 1.10 to 3.35). Conclusions: The results suggest no significant association between hyperglycemia in the ED and 30-day hospital revisits. In any patient with DM with a history of ASCVD or any ED visit in the previous year, there may be an increased risk of revisits.

Effect of Hemoglobin and Blood Glucose Levels on CT Perfusion Ischemic Core Estimation: A Post Hoc Analysis of the ESCAPE-NA1 Trial.

CT perfusion (CTP) maps can estimate the ischemic core in acute ischemic stroke based on distinctive cerebral blood flow thresholds. However, metabolic factors beyond perfusion influence the tissue tolerance to ischemia and the infarct growth rate. Underestimating the ischemic core volume (ICV) might result in overestimating the salvageable cerebral tissue and, consequently, overestimating the potential clinical benefits of reperfusion therapies. We aim to evaluate whether baseline hemoglobin and blood glucose levels influence the accuracy of baseline CTP ICV estimations. Large vessel occlusion stroke patients investigated with baseline CTP undergoing thrombectomy with near-complete reperfusion and without parenchymal hemorrhage from the ESCAPE-NA1 trial were included. Patients were subdivided into anemic (hemoglobin <130 g/L for men and <120 g/L for women) and nonanemic groups, and hyperglycemic (blood glucose level >7 mmol/L) and normoglycemic groups. Ischemic core underestimated volume (ICuV) was calculated: final infarct volume minus CTP-based ICV. The primary outcome was the presence of "perfusion scotoma" defined as ICuV ≥10 mL. Presence of "perfusion scotoma" and median ICuV were compared between anemic vs nonanemic and hyperglycemic vs normoglycemic patients using nonparametric tests and multivariable binary logistic regression with adjustment for baseline variables. One hundred sixty-two of 1,105 (15%) patients were included (median age 70.5 [interquartile range (IQR) 61-80.4], 50.6% women). The median ICuV was 7.26 mL (IQR 0-25.63). Seventy-eight (48%) patients demonstrated perfusion scotoma. Forty-two (25.7%) patients were anemic, and 65 (40.1%) were hyperglycemic. In univariable analysis, the hyperglycemic group had a higher prevalence of perfusion scotoma (65% [n = 40] vs 39% [n = 38], p = 0.006) and larger ICuV (17.79 mL [IQR 1.57-42.75] vs 6 mL [-0.31 to 12.51], p = 0.003) compared to normoglycemic patients. No significant ICuV differences between patients with and without anemia were seen. Multivariable regression analysis revealed an association between perfusion scotoma and hyperglycemia, adjusted odds ratio (OR) 2.48 (95% CI 1.25-4.92), and between perfusion scotoma and blood glucose levels, adjusted OR 1.19 (95% CI 1.03-1.39) per 1 mmol/L increase. In our study, CTP-based ischemic core underestimation was common and associated with higher baseline blood glucose levels. Individual metabolic factors beyond perfusion that critically influence the infarct growth rate should be considered when interpreting baseline CTP estimations of ischemic core.

Selective inhibition of T-type calcium channel preserves ischemic pre-conditioning mediated neuroprotection during cerebral ischemia reperfusion injury in diabetic mice.

Ischemic preconditioning (IPC) provides ischemic tolerance and neuroprotection during cerebral ischemia reperfusion (CI/R) injury. Diabetes abolishes the beneficial effects of conditioning phenomenon during CI/R. The study investigates the role of T-type calcium ion channel in IPC mediated protection during diabetes mellitus. The study employed Swiss Albino mice. Animals were divided into 3 normoglycaemic groups (Sham, CI/R, and IPC) and 4 hyperglycaemic groups (Sham, CI/R, IPC, and ML218 + IPC). CI/R injury was induced in Swiss Albino mice by occlusion of common carotid arteries followed by reperfusion. IPC was given prior to CI/R injury and diabetes was induced using streptozotocin (STZ). Animals were assessed for learning, memory, motor coordination, neurological function, cerebral infarction, edema, and histopathological alterations. Biochemical assessments were performed for calcium binding proteins (Calmodulin (CaM), calcium/calmodulin-dependent protein kinase II (CaMKII), and S100B), oxidative stress (4-hydroxy-2-nonenal (4-HNE)), glutathione (GSH), inflammation (nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), tumor necrosis factor (TNF-α), interleukin (IL-10)), inducible nitric oxide synthase (iNOS) levels, and acetylcholinesterase activity (AChE) in brain supernatants. NF-kB, iNOS, and S100B serum levels were also assessed. CI/R animals (normoglycemic and hyperglycaemic) showed impairment in learning, memory, motor coordination, and neurological function along with increase in cerebral infarction, edema, and histopathological alterations. Furthermore, increase in brain calcium-binding proteins, oxidative stress, inflammation, and AChE along with serum NF-kB, iNOS, and S100B levels were recorded in CI/R animals. IPC ameliorated CI/R induced behavioral, biochemical, and histopathological impairment, however no beneficial effects were observed in IPC (diabetic) mice. Administration of ML218 (10mg/kg; i.p.), a selective T-type calcium channel re-established the IPC mediated neuroprotection in CI/R diabetic animals. In conclusion, IPC-mediated neuroprotection was abolished in diabetic mice. T-type calcium ion channel antagonism plays an important role in the IPC-mediated neuroprotection during hyperglycaemia.

Association between glycemia and outcomes of neonates with hypoxic-ischemic encephalopathy: a systematic review and meta-analysis

ObjectivesThe research aimed to provide the most recent and comprehensive analysis and evidence update comparing outcomes in neonatal encephalopathy (NE) based on different glycemia levels.Patients and methodsA comprehensive search of Cochrane, PubMed, Embase, Web of Science, CNKI, and Wanfang databases was conducted until September 2023. The purpose was to identify research that examined the effects of hyperglycemia, hypoglycemia, and normoglycemia on NE outcomes. The hyperglycemic, normoglycemic and hypoglycemic group were compared. Outcomes measured were mortality, abnormal MRI, hearing or visual unfavorable outcomes, neurodevelopmental delay, cerebral palsy, and all unfavorable outcomes.ResultsThirteen literatures comprising 2,427 participants (1,233 with normoglycemia, 835 with hyperglycemia, and 359 with hypoglycemia) were considered. Pooled analysis showed more overall adverse outcomes, higher mortality and worse hearing or visual outcomes in the hyperglycemic and hypoglycemic group compared to the normoglycemic group. There was no notable distinction found in abnormal MRI and cerebral palsy among all groups. The hypoglycemic group exhibited greater neurodevelopmental delay than normoglycemia.ConclusionsMaintaining normal blood glucose levels in neonates with NE can help reduce the risk of adverse consequences such as hearing and visual impairment.

7481 Beyond the Operation Room: A Retrospective Study on Diabetes and Post-Operative Hyperglycemia Outcomes

Abstract Disclosure: P. Aron: None. T. Zaihra Rizvi: None. M. Hodge: None. J. Upadhyay: None. Introduction: Optimal, evidence based intraoperative and postoperative glycemic management may reduce poor surgical outcomes. Research design: This is a retrospective study from a single center to estimate quality gaps in perioperative glycemic management in patients with diabetes undergoing major surgery requiring general anesthesia between Oct 2022 and Dec 2022. Study Cohort: Patients &amp;gt; 18 years old, who underwent major surgery (&amp;gt;3 hrs) under general anesthesia, had diabetes mellitus based on Hba1c &amp;gt; 6.5% within last 1 year or as listed diagnosisThis is an ongoing study. We have currently looked at 79 patients of which 61 were in the hyperglycemic group (glucose &amp;gt; 180 mg/dL) and 18 in normoglycemic group (glucose &amp;lt; 180mg/dL) post-operatively. Methods: Baseline characteristics, perioperative outcomes, and operative details between the hyperglycemic and normoglycemic groups were compared using Kruskal-Wallis's rank sum test for continuous variables and χ2 or Fisher's exact tests using categorical variables. Results: Patients who were found to have hyperglycemia in the first 24 hours after surgery had a higher preop A1c of 7.4% vs 6.7% in the normoglycemia group (p-value = 0.047). They also had a higher BMI of 32 as compared to 30 respectively and a reduced GFR of 60 vs 73 in the normoglycemic group (P=0.069). 24 hours leading into surgery, the hyperglycemia group had a high average glucose of 196 mg/dL as compared to 135 mg/dL (p-value = 0.001). During the intraoperative period which lasted on average of 350 minutes (5.5 hours) there was an average glucose check of 3.2 times averaging 221 mg/dL for the hyperglycemia group compared to 2.2times averaging 174 mg/dL (P = 0.017). 62% of patients with intraoperative hyperglycemia DIDNOT receive IV insulin treatment in the hyperglycemic group. Steroid use was equal in both groups. 24 hours after surgery, patients in the hyperglycemia group had an average glucose reading of 252 mg/dL compared to 145 mg/dL in the normoglycemia group (P &amp;lt; 0.001).Endocrinology was not consulted in 87% of patients with hyperglycemia. Looking at our endpoints, readmission rate was 23% in the hyperglycemia group as opposed to 11% in normoglycemia. There were 4 patients who had a 90-day mortality from the hyperglycemia group compared to no patients in normoglycemia. 37% of patients had post-op complications in the hyperglycemia vs 22% in the euglycemia group (P 0.269). The hospital stay was the same for both groups averaging 8 days. Conclusions: Intraoperative hyperglycemia leads to poor outcomes. Formulating policy around insulin administration, frequency and monitoring of blood sugars during major surgeries and endocrine consultation in patients with Type 2 DM can achieve better glycemic management and postoperative outcomes. Presentation: 6/2/2024

Exploring the impact of oxidative stress, excitotoxicity, and apoptosis of retinal ganglion cells in streptozotocin-induced rats: A comprehensive investigation

Chronic hyperglycemia activates pathological molecular pathways, causing high inflammatory mediators, oxidative stress, and growth factors. This process contributes to retinal ganglion cell (RGC) apoptosis through the expression of N-methyl-D-aspartate (NMDA) receptors and nitric oxide (NO). This study analyzes the differential effect of NMDA receptor, NO expression, and RGC apoptosis in a hyperglycemic Wistar rat model. This research was designed as an experimental study, using a posttest only control group method. Fourteen male Wistar rats were split into two groups of seven: One received a single intraperitoneal injection of 50 mg/kg Streptozotocin (STZ) for hyperglycemia and the other served as the control. After 14 weeks of STZ injection, evaluations encompassed NMDA receptor, NO expression, and RGC apoptosis. Statistical analysis was performed using a parametric independent t-test and statistical significance was established at P &lt; 0.05. The hyperglycemic group showed much higher NMDA receptor levels (11.77 ± 3.36) than the control group (4.21 ± 2.16), with a P &lt; 0.001. The mean NO expression was 19.76 ± 8.41 in the hyperglycemic group, notably above the control group’s level of 4.01 ± 1.70 (P &lt; 0.001). The mean RGC apoptosis was 12.57 ± 3.26 in the hyperglycemic group and 9.00 ± 3.37 in the control group, without a significant difference, as indicated by a P = 0.068. These findings underscore the pronounced impact of hyperglycemia on NMDA receptors, NO expression, and RGC apoptosis, emphasizing potential targets for therapeutic interventions in diabetic retinopathy.

Quantitative brain [18F]FDG PET beyond normal blood glucose levels

Introduction SUV measurements from static brain [18F]FDG PET acquisitions are a commonly used tool in preclinical research, providing a simple alternative for kinetic modelling, which requires complex and time-consuming dynamic acquisitions. However, SUV can be severely affected by the animal handling and preconditioning protocols, primarily by those that may induce changes in blood glucose levels (BGL). Here, we aimed at developing and investigating the feasibility of SUV-based approaches for a wide range of BGL far beyond normal values, and consequently, to develop and validate a new model to generate standardized and reproducible SUV measurements for any BGL.Material and methods We performed dynamic and static brain [18F]FDG PET acquisitions in 52 male Sprague-Dawley rats sorted into control (n = 10), non-fasting (n = 14), insulin-induced hypoglycemia (n = 12) and glucagon-induced hyperglycemia (n = 16) groups. Brain [18F]FDG PET images were cropped, aligned and co-registered to a standard template to calculate whole-brain and regional SUV. Cerebral Metabolic Rate of Glucose (CMRglc) was also estimated from 2-Tissue Compartment Model (2TCM) and Patlak plot for validation purposes.Results Our results showed that BGL=100±6 mg/dL can be considered a reproducible reference value for normoglycemia. Furthermore, we successfully established a 2nd-degree polynomial model (C1=0.66E-4, C2=-0.0408 and C3=7.298) relying exclusively on BGL measures at pre-[18F]FDG injection time, that characterizes more precisely the relationship between SUV and BGL for a wide range of BGL values (from 10 to 338 mg/dL). We confirmed the ability of this model to generate corrected SUV estimations that are highly correlated to CMRglc estimations (R2= 0.54 2TCM CMRgluc and R2= 0.49 Patlak CMRgluc). Besides, slight regional differences in SUV were found in animals from extreme BGL groups, showing that [18F]FDG uptake is mostly directed toward central regions of the brain when BGLs are significantly decreased.Conclusion Our study successfully established a non-linear model that relies exclusively on pre-scan BGL measurements to characterize the relationship between [18F]FDG SUV and BGL. The extensive validation confirmed its ability to generate SUV-based surrogates of CMRglu along a wide range of BGL and it holds the potential to be adopted as a standard protocol by the preclinical neuroimaging community using brain [18F]FDG PET imaging.

Metformin and Caffeine’s Influence on Lipid Profile Indices of Streptozotocin-Induced Dyslipidemia in an Animal Model

Dyslipidemia has been linked to insulin resistance and hyperglycemia. Hyperglycemia, which is the outcome of either insufficient insulin production or insensitivity to insulin, is the hallmark of diabetes mellitus (DM). In this study, thirty-six (36) male Wistar rats with diabetes induced by streptozotocin were used to determine the effect of metformin and caffeine on blood glucose levels and lipid profile indices. The rats weighed between 150 and 200 grams and were split into six groups of six animals each at random. Group A was given unlimited access to chow (Grower feed) and water adlibitum. Group B was administered 60 mg/kg of streptozocin (STZ) without any medication, while Group C was given 60 mg/kg of STZ together with 50 mg/kg of metformin. Groups D and E were administered 60 mg/kg of streptozocin and 25 mg/kg and 50 mg/kg of caffeine, for a duration of 21 days respectively. Group F was given 50 mg/kg of caffeine together with 50 mg/kg of metformin for a duration of 21 days. After performing a post-hoc LSD comparison and using ANOVA to analyze the results, the lipid profile and blood glucose level were deemed significant at p&lt;0.05. A paired t-test was used to analyze body weight. Rats with diabetes had reduced body weight, whereas those receiving metformin and caffeine treatments had noticeably increased body weight. The findings demonstrated that whereas metformin and caffeine therapy greatly reduced blood glucose levels, STZ caused hyperglycemia in group B. However, diabetic rats had considerably higher levels of triglycerides (TG) and total cholesterol (TC), which were reduced by metformin and caffeine administration. HDL activity was considerably increased after treatment with metformin and caffeine, despite the rats' reduced HDL levels in group B. Rats with diabetes had considerably elevated levels of LDL and VLDL, and therapy with metformin and caffeine markedly restored their activity. The study shows that caffeine plus metformin may be utilized to control the lipid profile and blood glucose levels in diabetic rats.

Erythrocyte Oxidative Status in People with Obesity: Relation to Tissue Losses, Glucose Levels, and Weight Reduction.

This study aimed to investigate the impact of reductions in various body mass components on the erythrocyte oxidative status and glycemic state of people with obesity (PWO). A total of 53 PWO followed a six-month individualized low-calorie diet with exercise, during which anthropometric, biochemical, and oxidative parameters were measured. The participants were divided into groups based on weight (W), visceral fat area (VFA), total body water (TBW), and skeletal muscle mass (SMM) losses, as well as normoglycemia (NG) and hyperglycemia (HG). Weight reduction normalized glycemia and influenced erythrocyte enzyme activity. Regardless of the tissue type lost (VFA, TBW, or SMM), glutathione peroxidase activity decreased in all groups, accompanied by an increase in glutathione reductase activity. Lipofuscin (LPS) and malondialdehyde (MDA) concentrations decreased regardless of the type of tissue lost. The α-/γ-tocopherol ratio increased in those losing >10% body weight, >15% VFA, and >5% TBW. In the NG group, compared to the HG group, there was a decrease in glutathione peroxidase and an increase in glutathione reductase, with these changes being stronger in the HG group. The LPS and MDA concentrations decreased in both groups. Significant correlations were observed between glucose reduction and changes in catalase, retinol, and α-tocopherol, as well as between VFA reduction and changes in vitamin E, L-LPS, and the activities of L-GR and L-GST. This analysis highlights the complex interactions between glucose metabolism, oxidative state, and erythrocyte membrane integrity, crucial for understanding diabetes and its management. This study shows the significant metabolic adaptability of erythrocytes in response to systemic changes induced by obesity and hyperglycemia, suggesting potential therapeutic targets to improve metabolic health in obese individuals.

Critical Role of Preoperative Hyperglycemia in Association with GFAT-1 Expression in Resected Pancreatic Cancer.

Hyperglycemia is involved in malignant transformation of pancreatic cancer via the hexosamine biosynthetic pathway (HBP). However, few studies have verified this mechanism based on clinical data. This study investigated the complementary effects of hyperglycemia and HBP on pancreatic cancer prognosis using detailed clinical data. The study analyzed data of 477 patients with pancreatic cancer who underwent pancreatectomy between 2006 and 2020. The patients were divided into normoglycemia and hyperglycemia groups based on their HbA1c levels. Immunostaining for glutamine fructose-6-phosphate transaminase-1 (GFAT-1), the rate-limiting enzyme in HBP, CD4, CD8, and Foxp3, was performed to evaluate the association between survival outcomes, HBP, and local tumor immunity. Overall survival (OS) was significantly poorer in the hyperglycemia group than in the normoglycemia group (mean survival time [MST]: 35.0 vs. 47.9months; p = 0.007). The patients in the hyperglycemia group with high GFAT-1 expression had significantly poorer OS than those with low GFAT-1 expression (MST, 49.0 vs. 27.6months; p < 0.001). However, the prognosis did not differ significantly between the patients with high and low GFAT-1 expression in the normoglycemia group. In addition, the patients with hyperglycemia and high GFAT-1 expression had fewer CD4+ (p = 0.015) and CD8+ (p = 0.017) T cells and a lower CD8+/Foxp3+ ratio (p = 0.032) than those with hyperglycemia and low GFAT-1 expression. The patients with hyperglycemia and high GFAT-1 expression levels had an extremely poor prognosis. Furthermore, the tumors in these patients were characterized as immunologically cold tumors.

Abstract Tu028: NADPH Oxidase Inhibition Antagonizes Endothelial Pro-inflammatory and Pro-oxidant Signaling Resulting in Enhanced Coronary Vasorelaxation in Diabetic Models

Introduction: NADPH oxidase (NOX) overactivation and reactive oxygen species amplification may underlie worse cardiac outcomes in patients with diabetes. Our group has shown impaired endothelium-dependent coronary vasodilation in diabetes, with restored endothelial function following NOX inhibition. Persistently high levels of oxidative stress may be driving this impaired coronary microvascular reactivity by altering small-conductance potassium channel activity. We hypothesized that NADPH oxidase inhibition would be vasoprotective through reductions in pro-oxidant and pro-inflammatory signaling. Methods: Human coronary arterial endothelial cells (HCAECs) were obtained from diabetic (D) and nondiabetic (C) patients (N = 4 per group). HCAECs were cultured in normo- or hyperglycemic conditions, with one hyperglycemic group receiving NADPH oxidase inhibitor apocynin (DT). Molecular signaling was assessed using immunoblotting. Results: Diabetes resulted in significantly increased pro-oxidant markers, including NOX 4 (p = 0.005), phosphorylated endothelial nitric oxide synthase (p-eNOS) (p = 0.007), and eNOS (p = 0.003). Pro-inflammatory Nrf2 was also increased (p = 0.0003), with a trend toward increased NFkB (p = 0.09) in D compared to C. Antioxidant peroxiredoxin (PRDX) 1 was significantly reduced in D compared to C (p = 0.02). NOX inhibition rescued these effects, with reversed trends in NOX 4 (p = 0.008), p-eNOS (p = 0.03), and PRDX 1 (p = 0.02) following apocynin treatment. NOX inhibition resulted in de novo decrease in NOX 1 in DT when compared to D (p = 0.008) and C (p = 0.02), and decrease in phosphorylated NFkB (p-NFkB) when compared to D (p = 0.02). There was a trend toward decreased total NFkB (p = 0.07) and p-NFkB:NFkB ratio (p = 0.06) and increased antioxidant thioredoxin (TXN) 2 (p = 0.05) in diabetic cells following treatment. Antioxidant superoxide dismutase (SOD) 2 (p = 0.01) and TXN 1 (p = 0.02) were increased in D when compared to C, while apocynin treatment reversed these changes (SOD 2, p = 0.0006; TXN 1, p = 0.04). There were no significant differences in NOX 2, SOD 1, catalase, PRDX 2, or PRDX 3 between the groups. Conclusions: Apocynin overall suppressed pro-oxidant and pro-inflammatory signaling in human diabetic coronary endothelial cells, resulting in improved coronary endothelium-dependent vasorelaxation. Cardioprotective strategies that incorporate NADPH oxidase inhibition in the setting of diabetes warrant further investigation.

Effect of Camellia flava (Pitard) Sealy flower extract on the degeneration of Islets of Langerhans and insulin resistance in alloxan-induced hyperglycemia model on Swiss albino mice

Diabetes has always been a matter of concern to health experts as well as the community due to the increasing number of patients with diabetes and the severe consequences it may cause. Many attempts have been made to discover new treatment options for diabetes, and herbal medicines are currently considered to have great potential. This study was conducted to evaluate the effect of Camellia flava flower extract on the degeneration of the islets of Langerhans and insulin resistance in an alloxan-induced hyperglycemia model in Swiss albino mice. Hyperglycemic conditions were induced by alloxan (55 mg/kg, i.v.). The animals were then treated with glibenclamide (10 mg/kg, p.o.) and flower extract at doses of 1.09 and 2.19 g/kg, p.o. The results showed that the blood glucose, AUC, HbA1c, and HOMA-IR levels of two groups of mice receiving flower extract were considerably lower than those of the hyperglycemic untreated group (p &amp;lt; 0.05). The body weights of these two groups were also lower than the untreated group on the last day of the experiment, though the differences were not significant (p &amp;gt; 0.05). However, this was not observed when assessing insulin levels as well as relative organ weights. In biochemical tests, creatinine and AST and ALT concentrations were evaluated. There was no significant variation in creatinine and AST concentrations between the five experimental groups, whereas mice treated with glibenclamide and flower extract at both doses showed a remarkable decline in ALT concentration (p &amp;lt; 0.05). The hepatic histomicrographs were consistent with ALT results, while the H&amp;E staining of kidneys showed no difference between groups. Histomicrographs of the pancreas revealed that the treatment groups using glibenclamide and flower extract had larger islets of Langerhans than those of the alloxan-treated group. Based on these results, this study demonstrated that Camellia flava flower extract exerted several beneficial effects, including blood sugar level reduction, weight loss promotion, and organ protection, hence making it a new potential herbal medication for the management of diabetes.

Importance of Blood Glucose Measurement for Predicting the Prognosis of Long COVID: A Retrospective Study in Japan.

Purpose: The present study aimed to clarify the effects of a hyperglycemic condition on the clinical consequences of long COVID. Methods: Among 643 patients who visited the outpatient clinic of our hospital from February 2021 to September 2023, long COVID patients were classified into a hyperglycemic (HG) group with casual blood glucose levels above 140 mg/dL and a normoglycemic (NG) group. The patients' backgrounds, clinical symptoms, health status including the QOL evaluation scale (EQ-5D-5L), self-rating depression scale (SDS), and F-scale questionnaire (FSSG), blood test data, and recovery periods were analyzed. Results: The NG group included 607 patients with long COVID and the HG group included 36 patients with long COVID. Patients in the HG group were older than those in the NG group (55 vs. 41 years; p < 0.001) and included a larger percentage of males (67% vs. 44%; p = 0.009). The HG group had a larger percentage of patients with moderate-to-severe conditions in the acute infection phase (28% vs. 12%; p = 0.008), a higher BMI (25 vs. 22 kg/m2; p < 0.001), higher blood pressure (138/81 vs. 122/72 mmHg; p < 0.001), and a larger percentage of patients with an alcohol drinking habit (53% vs. 34%; p = 0.031). Long COVID symptoms and self-rated scales were not differed between the two groups; however, the laboratory data showed that liver and renal functions and metabolic data were significantly worse in the HG group. Although there was no apparent difference between the two groups in duration from the infection to the first visit, the HG group had a significantly longer period of recovery from long COVID (median period of 421 vs. 294 days; p = 0.019). Conclusion: A hyperglycemic state associated with other lifestyle-related diseases is associated with the prolongation of recovery from long COVID.

SARS-CoV-2 Infection Positively Correlates with Hyperglycemia and Inflammatory Markers in COVID-19 Patients: A Clinical Research Study.

Diabetes mellitus (DM) is a common comorbidity in COVID-19 subjects. Hyperglycemia at hospital admission identified as a major risk factor and is responsible for poor prognosis. Hematological and inflammatory parameters have been recognized as predictive markers of severity in COVID-19. In this clinical study, we aimed to assess the impact of hyperglycemia at hospital admission on hematological and several inflammatory parameters in COVID-19 patients. A total of 550 COVID-19 subjects were primarily categorized into two major groups (normoglycemic and hyperglycemic) based on random blood sugar levels. On the first day of hospitalization, subjects' oxygen saturation, random blood sugar, hematological variables, and inflammatory parameters were recorded. The hyperglycemic group exhibited higher levels of serum ferritin, total leukocyte count (TLC), lactate dehydrogenase (LDH), neutrophil count, and neutrophil-to-lymphocyte ratio (NLR). In contrast, oxygen saturation and lymphocyte count were lower compared to the normoglycemic group. Significantly elevated levels of hematological variables (TLC, neutrophil count, NLR) and inflammatory parameters (serum ferritin) were observed in the hyperglycemic group. Among inflammatory parameters, only serum ferritin levels showed statistical significance. This study supports the clinical association between hyperglycemia and an increased severity of COVID-19. Consequently, the identification of these parameters is a crucial and valuable prognostic indicator for assessing disease severity in hyperglycemic subjects.

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.

Association of serum irisin levels with glucose and lipid metabolism among adolescents in Yinchuan City from 2017 to 2020

To explore the relationship between serum irisin levels and glucose and lipid metabolism among adolescents in Yinchuan City. From 2017 to 2020, a conbination of convenient sampling and stratified cluster random sampling method were used to select 1219 adolescents aged 12 to 18 years old in Yinchuan City as research subjects. The height and weight were measured using the height and sitting height meter and the bioelectrical impedance analyzer. Blood indicators such as fasting plasma glucose(FPG), totalcholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C) and high-density lipoprotein cholesterol(HDL-C) were measured using fully automatic biochemical analyzer. Serum irisin levels were measured by enzyme-linked immunosorbent assay(ELISA). Binary logistic regression was used to analyze the correlation between irisin and abnormal glucose and lipid metabolism. The FPG, TC, HDL-C and LDL-C levels of subjects in the highest tertile of irisin levels were significantly lower than those of subjects in the lowest tertile of irisin levels(F values were 5.13, 3.15, 3.07 and 5.01, P&lt;0.05), and the differences were statistically significant(all P&lt;0.05). The serum irisin levels in the hyperglycemia group(t=2.87, P&lt;0.01), hypercholesterolemia group(t=2.36, P=0.02) and hyperLDL-Cemia group(t=2.34, P=0.02) were significantly lower than those in the normoglycemia group, normal TC group and normal LDL-C group. Meanwhile, the irisin level in the low HDL-Cemia group(t=-2.57, P=0.01) was significantly higher than that in the normal HDL-C group, and the differences were statistically significant(P&lt;0.05). Participants in the highest tertile of irisin had 0.51, 0.49 and 0.50 times the risk of hyperglycemia(OR=0.51, 95%CI 0.29-0.87), hypercholesterolemia(OR=0.49, 95%CI 0.27-0.89) and hyperLDL-cemia(OR=0.50, 95%CI 0.25-0.99) compared with those in the lowest tertile. Low levels of irisin are associated with the occurrence of hyperglycemia, hypercholesterolemia, and hyperLDL-Cemia in adolescents.