Diabetic Group Research Articles

Study the role of xanthine oxidase inhibitor, allopurinol in experimentally induced steatohepatitis

Nonalcoholic steatohepatitis (NASH) is a chronic liver disease which can lead to cirrhosis and hepatic failure. It is observed in patients with both type 1 and type 2 diabetes mellitus (T1DM, T2DM). Allopurinol, a xanthine oxidase inhibitor that is widely used in clinical practice, has been demonstrated to reduce hepatic oxidative stress and attenuate acute liver injury which may be through activation of antioxidant pathways. This work aimed at investigating the role of Allopurinol (ALP) in attenuation of type 1 diabetes associated with Nonalcoholic fatty liver disease (NAFLD) and exploring the possible molecular mechanism by which ALP attenuates NASH in type 1 diabetes. Forty-five adult male albino rats were included in the study. They were randomly allocated to 3 equal groups: group I (control), Group II (diabetic animals), Group III (diabetic animals with allopurinol treatment). At the end of this experimental study measurements of serum glucose, ALT, AST, cholesterol, triglyceride, serum levels of uric acid, malondialdehyde (MDA), serum superoxide dismutase (SOD) were done. Histological analysis of liver tissue to diagnose steatohepatitis and gene expression of nuclear factor-erythroid-2- related factor-2 (Nrf2) & TNFα were done. Diabetic rates treated with allopurinol (group III) showed decrease in serum levels of ALT, AST, cholesterol, uric acid and MDA compared to diabetic rat group. As regards TNF, gene expression was significantly decreased in group III compared to group II. This study also demonstrated that Nrf2α was significantly increased in group III compared to group II. Allopurinol also, ameliorated the histopathological changes observed in group II. In conclusion, allopurinol treatment increases the Nrf2 gene expression in the liver of STZ-induced diabetic rats and ameliorates steatohepatitis through modulation of TNF-α gene expression. Allopurinol could be a candidate for prevention or treatment of NAFLD.

Influence of impaired glucose tolerance and type 2 diabetes on the multimorbidity cluster of cardiovascular disease and cancer: a post hoc analysis of the Da Qing Diabetes Prevention Outcome Study.

This study explored the influence of type 2 diabetes and impaired glucose tolerance (IGT) on the risk of the multimorbidity cluster of cardiovascular disease (CVD) and cancer. A total of 1629 participants in the Da Qing Diabetes Prevention Outcome Study were recruited in the present analysis, including normal glucose tolerance (NGT, N = 492), IGT (N = 540), and newly diagnosed type 2 diabetes (N = 597) groups. Cox proportional hazards analyses were performed to assess the relationship between NGT, IGT, and newly diagnosed type 2 diabetes and the risk of the multimorbidity cluster of CVD and cancer. The incidence rates for multimorbidity cluster CVD and cancer were 1.25, 3.17, and 3.23 per 1000 person-years in people with NGT, IGT, and the newly diagnosed type 2 diabetes groups, respectively, over 34-year follow-up. Cox analysis revealed that diabetes status (as time-dependent variable) was significantly associated with the subsequent increased risk of multimorbidity cluster of CVD and cancer compared with non-diabetes (hazard ratios [HR] = 2.55, 95% confidence interval [CI] 1.51-4.31) after adjustment of potential confounders. Similar analysis showed that this risk was significantly higher in the IGT and newly diagnosed type 2 diabetes groups compared with NGT, with HR of 3.28 (95% CI 1.83-5.87) and HR of 3.90 (95% CI 2.14-7.09), respectively. Whereas compared diabetes with IGT group, this risk was not significantly different. Similar to newly diagnosed type 2 diabetes, IGT is significantly associated with an increased risk of the multimorbidity cluster of CVD and cancer compared with NGT. This finding highlights the urgent need for an active detection of IGT and effective prevention and management of diabetes.

Antioxidant and Antiapoptotic Effects of Selenium And Nano Selenium-Loaded Exosomes on Hepatic Dysfunction of Type 1 Diabetic Rats.

Mesenchymal stem cells-derived exosomes (MSCs-EXs) applications have brought a key breakthrough in treating type 1 diabetes mellitus (T1DM) and its diabetic complications. However, various recent strategies aimed to construct prominent engineered EXs with greater precision and higher efficiency for diabetes syndrome were conducted. In this research, we seek to enhance the medicinal potentialities of MSCs-EXs on type 1 diabetic rats' hepatic complications, via loading with either selenium (Se) or nano selenium (NSe) particles. For consecutive 4-weeks, rats were divided into 8 groups as; control, EXs, EXs + Se, EXs + NSe, STZ-diabetic (D), D + EXs, D + EXs + Se, and D + EXs + NSe groups. The three diabetic-treated groups manifested a significant reduction in hepatic contents of oxidative stress (OS) (MDA, NO, and H2O2) inflammatory (IL-6, TNF-α, and TGF-β), and apoptotic (P53, BAX, caspase-3, and Bcl2) markers, with marked elevation in hepatic antioxidant levels (GSH, GPX, SOD, and CAT). Such results were supported by the marked diminish in serum total proteins, liver function enzymes (AST, ALT, and bilirubin), and both serum and liver lipid profile fractions. In addition, hepatic histological examination showed marked improvement in liver architecture of all treated diabetic rats' groups, compared to diabetic untreated rats. Significantly, diabetic rats with EXs loaded with NSe exhibited the most therapeutic superiority.

Effect of Different Rates of Rambutan Peel Extract on Visfatin and Cardiac Troponin I Response in Type 2 Diabetic Rats Induced with Streptozotocin

Background: The aim of this study was to investigate the effects of STZ (Streptozotocin) and Rambutan peel extract (RPE) on serum visfatin and cardiac response in experimental Type 2 diabetic rats. Methods: In this study, 64 adult male Wistar albino rats, aged between 8-10 weeks, were used. 8 groups were randomly selected, each containing 8 rats as Control (C), R100 (RPE 100 mg/kg group given with oral gavage route of administration (OGRA), R200 (RPE 200 mg/kg group given with OGRA), R300 (RPE 300 mg/kg group given with OGRA); Diabetes Control (DC): STZ 50 mg/kg i.p administered group, DR100 (D+100 mg/kg JPE), DR200 (D+200 mg/kg JPE), DR300 (D+300 mg/kg JPE). The study lasted a total of 31 days, including adaptation (7 days), induction of diabetes (3 days), and trial period (21 days). Blood samples were taken from the tail vein (vena caudalis) of all subjects on days 0 and 21 of the study. Visfatin and cTnI levels in the serum samples were measured and evaluated by ELISA method. Result: While the increase in mean serum visfatin and cTnI levels in diabetic groups was seen mostly in DC groups, the most significant decrease in mean serum visfatin level due to the addition of RPE was determined in DR100 groups (p less than 0.01).As a result, it was concluded that the administration of 100 mg/kg RPE in rats had no adverse effects. It was concluded that RPE, which has a cardioprotective effect by regulating the visfatin response that plays a role in the development of diabetes, may be useful in supporting the impaired cardiovascular system function that occurs in diabetes.

Abstract 4121568: The Influence of Cardiovascular Health on Atherosclerotic Cardiovascular Disease Progression and Life Expectancy Among Individuals with Type 2 Diabetes

Objective: This study aims to evaluate whether cardiovascular health (CVH) plays a similar role in the transition from a healthy state to atherosclerotic cardiovascular disease (ASCVD) and subsequent mortality rates in diabetic patients compared to those without diabetes. It also evaluates the effectiveness of CVH in reducing diabetes-related ASCVD risks and enhancing ASCVD-free life expectancy. Research design and methods: This cohort study included 176,669 adults from the UK Biobank, among whom 10,109 (22.3%) were diagnosed with type 2 diabetes mellitus (T2DM). CVH was assessed using the Life's Essential 8 score, encompassing diet, physical activity, smoking, sleep, BMI, blood lipids, blood glucose, and blood pressure. CVH scores were categorized into low, moderate, and high levels based on their distribution among diabetic patients. The main outcomes were the transitions from no ASCVD to the onset of ASCVD and then to mortality, as well as the ASCVD-free life expectancy. Results: In patients with T2DM, high CVH levels were associated with lower ASCVD risk (HR: 0.55, 95% CI: 0.45-0.68 for women; HR: 0.57, 95% CI: 0.50-0.65 for men) and reduced mortality in those with ASCVD (HR: 0.62, 95% CI: 0.39-0.98 for women; HR: 0.62, 95% CI: 0.48-0.79 for men), compared to the low CVH group. No significant difference in CVH's effect on ASCVD and mortality was observed between diabetic and non-diabetic groups. When compared with non-diabetic individuals, no excess risk was observed in incident ASCVD and post-ASCVD mortality among diabetic patients with high CVH. At the age of 40, women with low CVH were expected to live 38.5 years (38.0-39.1) free from ASCVD, which increased to 42.9 years (42.4-43.5) for those with high CVH, while non-diabetic women were predicted to have an ASCVD-free life expectancy of 44.1 years (43.5-44.6). For men at the age of 40, those with low CVH had an ASCVD-free life expectancy of 32.0 years (31.3-32.6), which rose to 37.9 years (37.4-38.6) with high CVH. Non-diabetic men were expected to live 38.3 years (37.7-39.0) free from ASCVD. Notably, life expectancy with ASCVD did not increase with higher CVH levels in both genders. Conclusions: Our findings suggest that the American Heart Association’s recommendations for promoting CVH, initially designed for the general population, are also beneficial for individuals with T2DM. Adopting these guidelines can help mitigate ASCVD progression and enhance life expectancy in diabetic patients.

Innovating Diabetes Care in Pregnancy: Do group care models improve outcomes and equity?

Shared medical appointments (SMAs) for diabetes and group prenatal care (GPC) for pregnant patients, have emerged as innovative care delivery models. They have the potential to transform diabetes care by overcoming many of the time limitations of traditional one-on-one clinical visits. There is compelling evidence that SMAs improve glycemic control for non-pregnant patients with diabetes, GPC reduces Black/White health disparities in preterm birth, and Diabetes Group Prenatal Care increase postpartum glucose tolerance test uptake among patients with gestational diabetes mellitus. GPC models standout as one of few interventions that reduce racial health disparities, which we hypothesize occurs because they inadvertently exert their effect on both the patient and clinician through a 20+ hour meaningful shared experience. This Perspective explores the evidence for SMA and GPC in diabetes and pregnancy, theoretical underpinnings of the models, their potential to promote more equitable care, and future directions from my Perspective, as a high-risk obstetrician and 2019 ADA Pathway Accelerator award recipient.

Impact of Green Tea Consumption and Its Extracts on Fat Reduction and Weight Loss

Introduction: Obesity and overweight are major health problems and challenges in the world today. It is the task of modern pharmacology, medicine and dietetics to search for new therapeutic methods to reduce body weight and body fat. Green tea has been a focus of research on its effects on weight reduction for many years. This article will analyse the available studies on the effectiveness of green tea on body weight and body fat reduction in obese and overweight people. Aim of the study: The aim of this review is to analyse the available literature in order to answer the question of whether green tea and green tea extracts (GTE) have an effect on weight loss, body fat reduction and associated metabolic processes.Materials and method: For a comprehensive review on the effects of green tea on weight and body fat reduction, we reviewed studies and literature available in databases such as PubMed and Google Scholar by searching through keywords such as ‘green tea’, ‘obesity’, ‘fat’, ‘weight loss’, ‘matcha’.Conclusion: green tea and its isolated substances such as epigallocatechin-3-O-gallate (EGCG) appear to have a positive effect on weight and body fat reduction in obese and overweight individuals. It is likely that consumption of green tea extract increases fat oxidation during exercise. In addition, supplementation had a positive effect in a group of diabetics, polycystic ovary syndrome and metabolically stressed patients. The best effects from supplementation were obtained by those who additionally had physical activity. It is suggested that research on green tea, especially on matcha, should continue, as very little reliable research has been produced on this topic

Biochemical Studies of Averrhoa carambola Ethanol Leaf and Fruit Extracts on Alloxan-induced Diabetic Rats

The use of herbal medicines has always been an option to treat diseases such as diabetes cancer and other ailments. This study aimed to evaluate the effect of Averrhoa carambola leaf and its fruit ethanol extracts on biochemical parameters and histopathology features. Forty five albino rats were assigned into 9 groups of 5 rats each. Except for the normal control group, others were induced to be diabetic by a single intraperitoneal injection of alloxan. Group 1 (normal control) and Group 2 (diabetic untreated) received water. Group 3 received 2.5mg/kg glibenclamide, Groups 4-9 received graded doses (250mg/kg, 500mg/kg and 750mg/kg) of leaf and fruit extracts of Averrhoa carambola. Treatment lasted 14days. At the end of the treatment, blood samples and organ (pancreas) were collected from the animals for biochemical and histopathological evaluation. Treatment of alloxan-induced diabetic rats significantly (p<0.05) reduced the glucose concentration across all treated groups. Following induction of diabetic mellitus, the serum activities of liver enzymes (Alanine amino transferase, Aspartate aminotransferase and Alkaline phosphatase), low-density lipoprotein cholesterol (LDL-C) and triglyceride were significantly (p<0.05) elevated in diabetic untreated group with corresponding reduction in serum protein, albumin and high-density lipoprotein cholesterol (HDL-C) compared to the normal control and treated groups. However, the fruit extracts exhibited a high increase in urea and creatinine levels especially at dose of 750mg/kg body weight when compared with the leaf though not significantly higher than the diabetic untreated group. From histopathology studies, the groups treated with the leaf extract of Averrhoa carambola showed greater structural improvement and an increase in pancreatic islet cells. Therefore this study showed that although ethanol extracts of Averrhoa carambola leaf and fruit have antidiabetic properties, the leaf extract possesses more antidiabetic effect.

Semaglutide Ameliorates Diabetic Neuropathic Pain by Inhibiting Neuroinflammation in the Spinal Cord

Glucagon-like peptide 1 (GLP-1) receptor agonists are frequently used to treat type 2 diabetes and obesity. Despite the development of several drugs for neuropathic pain management, their poor efficacy, tolerance, addiction potential, and side effects limit their usage. Teneligliptin, a DPP-4 inhibitor, has been shown to reduce spinal astrocyte activation and neuropathic pain caused by partial sciatic nerve transection. Additionally, we showed its capacity to improve the analgesic effects of morphine and reduce analgesic tolerance. Recent studies indicate that GLP-1 synthesized in the brain activates GLP-1 receptor signaling pathways, essential for neuroprotection and anti-inflammatory effects. Multiple in vitro and in vivo studies using preclinical models of neurodegenerative disorders have shown the anti-inflammatory properties associated with glucagon-like peptide-1 receptor (GLP-1R) activation. This study aimed to investigate the mechanism of antinociception and the effects of the GLP-1 agonist semaglutide (SEMA) on diabetic neuropathic pain in diabetic rats. Methods: Male Wistar rats, each weighing between 300 and 350 g, were categorized into four groups: one non-diabetic sham group and three diabetic groups. The diabetic group received a single intraperitoneal injection of streptozotocin (STZ) at a dosage of 60 mg/kg to induce diabetic neuropathy. After 4 weeks of STZ injection, one diabetic group was given saline (vehicle), and the other two were treated with either 1× SEMA (1.44 mg/kg, orally) or 2× SEMA (2.88 mg/kg, orally). Following a 4-week course of oral drug treatment, behavioral, biochemical, and immunohistochemical analyses were carried out. The mechanical allodynia, thermal hyperalgesia, blood glucose, advanced glycation end products (AGEs), plasma HbA1C, and spinal inflammatory markers were evaluated. Results: SEMA treatment significantly reduced both allodynia and hyperalgesia in the diabetic group. SEMA therapy had a limited impact on body weight restoration and blood glucose reduction. In diabetic rats, SEMA lowered the amounts of pro-inflammatory cytokines in the spinal cord and dorsal horn. It also lowered the activation of microglia and astrocytes in the dorsal horn. SEMA significantly reduced HbA1c and AGE levels in diabetic rats compared to the sham control group. Conclusions: These results indicate SEMA’s neuroprotective benefits against diabetic neuropathic pain, most likely by reducing inflammation and oxidative stress by inhibiting astrocyte and microglial activity. Our findings suggest that we can repurpose GLP-1 agonists as potent anti-hyperalgesic and anti-inflammatory drugs to treat neuropathic pain without serious side effects.

Modified FIB-4 Index in Type 2 Diabetes Mellitus with Steatosis: A Non-Linear Predictive Model for Advanced Hepatic Fibrosis

Background: The Fibrosis-4 (FIB-4) index is widely recommended as a first-tier method for screening advanced hepatic fibrosis; however, its diagnostic performance is known to be suboptimal in patients with Type 2 diabetes mellitus (T2DM). We aim to propose a modified FIB-4, using the parameters of the existing FIB-4, tailored specifically for diabetic patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: A total of 1503 patients who underwent liver biopsy were divided into T2DM (n = 517) and non-T2DM (n = 986) groups. The model was developed using multiple regression analysis in the derivation cohort and validated in the validation cohort. Diagnostic accuracy was evaluated using the area under the receiver operating characteristic (AUC) curves. Results: Among the 1503 individuals, those with T2DM were older, more likely to be male, and had a higher prevalence of advanced hepatic fibrosis (≥F3) compared to non-T2DM individuals. Independent risk factors for advanced fibrosis in T2DM included age, AST, AST/ALT ratio, albumin, triglycerides, and platelet count. The optimized FIB-4 model for T2DM with MASLD (Diabetes Fibrosis Index) demonstrated superior diagnostic accuracy (AUC 0.771) compared to the FIB-4 (AUC 0.735, p = 0.012). The model showed a higher negative predictive value than the original FIB-4 across all age groups in the diabetic group. Conclusions: The newly optimized FIB-4 model for T2DM with MASLD (Diabetes Fibrosis Index), incorporating a non-linear predictive model, improves diagnostic performance (AUC) and the negative predictive value in MASLD with T2DM.

Ameliorating Immune-dependent Inflammation and Apoptosis by Targeting TLR4/MYD88/NF-ᵰ5B Pathway by Celastrol Mitigates the Diabetic Reproductive Dysfunction.

This study aimed to examine the protective effect of celastrol on testicular dysfunction in diabetic rats and the potential underlying mechanisms. All rats included in the study were divided into four groups: a control group treated with sodium citrate buffer and vehicle), a celastrol-treated control group, a streptozotocin (STZ)-induced diabetic group following insulin resistance, and a celastrol-treated diabetic group. Serum glucose, triglyceride, total cholesterol, high-density lipoprotein cholesterol, interleukin (IL)-1β, tumor necrosis factor-alpha, and testosterone levels were measured. In addition, the levels of testicular homogenate superoxide dismutase and malondialdehyde were assessed. Furthermore, testicular tissue relative TLR4, NF-ᵰ5B, and MYD88 expression were quantitatively measured using polymerase chain reaction. Histopathological and immunohistochemical studies were also conducted. The results revealed that treatment with celastrol significantly reduced TLR4, MyD88, NF-ᵰ5B expressions and the levels of inflammatory mediators such as tumor necrosis factor-alpha and IL-1ᵯD in the testicular tissue of treated rats. These findings suggest has the potential to be effective in the treatment of diabetes-induced testicular injury by inhibiting testicular inflammation, apoptosis, and oxidative stress.

Reliability and utility of blood glucose levels in the periodontal pockets of patients with type 2 diabetes mellitus: a cross-sectional study.

Several studies have measured gingival blood glucose (GBG) levels, but few have confirmed systematic bias using Bland-Altman analysis. This study compared the effectiveness of GBG levels with that of fingertip blood glucose (FTBG) levels using Bland-Altman and receiver operating characteristic (ROC) analyses. A total of 15 healthy volunteers and 15 patients with type 2 diabetes were selected according to inclusion and exclusion criteria. Each group comprised eight male and seven female participants. The GBG and FTBG levels were measured using a self-monitoring blood glucose device after periodontal examination. Pearson's product‒moment correlation and simple linear regression analyses were performed. In addition, Bland‒Altman analysis was also performed to assess the degree of agreement between the two methods. ROC analysis was conducted to determine the sensitivity, specificity, and cutoff values for patients with diabetes. The area under the ROC curve (AUC) was used to identify significant differences. The mean GBG and FTBG levels were 120 ± 44.8 mg/dL and 137 ± 45.1, respectively, for the whole sample. The mean GBG and FTBG levels were 145 ± 47.2 mg/dL and 163 ± 49.1, respectively, in the diabetes group. The mean GBG and FTBG levels in the nondiabetes group were 95.3 ± 25.2 and 111 ± 18.8, respectively. Patients with diabetes were more likely to have a probing pocket depth (PPD) of ≥4 mm at the sampled site. Pearson's product‒moment correlation and simple linear regression analyses revealed a significant correlation between the GBG and FTBG measurements. Bland-Altman analysis revealed that GBG and FTBG measurements differed significantly among all participants; however, no significant differences were observed among the patients with diabetes (mean difference (MD) ± standard deviation (SD) = -18.1 ± 34.2, 95% confidence interval (CI) [-37.0 to 0.88]) or among the participants with a PPD of ≥4 mm (MD ± SD = -15.2 ± 30.4, 95% CI [-30.8 to 0.43]). The sensitivity, specificity, and cutoff values of the GBG measurements for detecting diabetes were 80%, 93%, and 123.5 mg/dL, respectively. The sensitivity, specificity, and cutoff values of the FTBG measurements for detecting diabetes were 73%, 87%, and 134.0 mg/dL, respectively. No significant differences were observed between the AUCs (0.078, 95% CI [-0.006 to 0.161]). The GBG measurements aligned with the FTBG measurements in the patients with diabetes and among the participants with a PPD of ≥4 mm. Patients with diabetes were more likely to have a PPD of ≥4 mm at the sampled site, GBG levels can be used to screen for type 2 diabetes in dental clinics.

Influence of Diabetes Mellitus on Neurological Recovery in Older Patients With Cervical Spinal Cord Injury Without Bone Injury: A Retrospective Multicenter Study.

Retrospective study. To investigate the impact of diabetes mellitus on neurological recovery and determine the relationship between moderate-severe diabetes and neurological recovery in patients with cervical spinal cord injury (CSCI) without bone injury. A retrospective study was conducted on 389 consecutive patients aged ≥65 years with CSCI without bone injury across 33 medical institutes. The patients were divided into a nondiabetic group (n = 270) and a diabetic group (n = 119). Neurological outcomes were compared between the two groups through propensity score matching. The impact of moderate-severe diabetes (defined as hemoglobin A1c ≥ 7.0% or requiring insulin treatment) on neurological recovery was evaluated through multiple linear regression analysis. Propensity score matching revealed no significant differences between the diabetic and nondiabetic groups in terms of American Spinal Injury Association (ASIA) impairment scale grade and mean total ASIA motor scores (AMS) at 6 months post-injury. Multiple linear regression analysis indicated that age on admission (B = -0.34; 95% confidence interval [CI], -0.59 to -0.08; P = 0.01), dementia (B = -16.50; 95% CI, -24.99 to -8.01; P < 0.01), and baseline total AMS (B = -0.62; 95% CI, -0.72 to -0.51; P < 0.01) were negative predictors of neurological recovery at 6 months post-injury. The presence of moderate-severe diabetes did not influence neurological recovery at 6 months post-injury. Diabetic patients with CSCI without bone injury achieved improvements in neurological function comparable to those of nondiabetic patients. Moderate-severe diabetes did not affect neurological recovery in patients with CSCI without bone injury.

Cardioimmunology in Health and Diseases: Impairment of the Cardio-Spleno-Bone Marrow Axis Following Myocardial Infarction in Diabetes Mellitus.

A comprehensive understanding of the cardio-spleen-bone marrow immune cell axis is essential for elucidating the alterations occurring during the pathogenesis of diabetes mellitus (DM). This study investigates the dynamics of immune cell kinetics in DM after myocardial infarction (MI) over time. MI was induced in diabetic and healthy control groups using C57BL/N6 mice, with sacrifices occurring at days 1, 3, 7, and 28 post-MI to collect heart, peripheral blood (PB), spleen, and bone marrow (BM) samples. Cell suspensions from each organ were isolated and analyzed via flow cytometry. Additionally, the endothelial progenitor cell-colony-forming assay (EPC-CFA) was performed using mononuclear cells derived from BM, PB, and the spleen. The results indicated that, despite normal production in BM and the spleen, CD45+ cells were lower in the PB of DM mice at days 1 to 3. Further analysis revealed a reduction in total and pro-inflammatory neutrophils (N1s) in PB at days 1 to 3 and in the spleen at days 3 to 7 in DM mice, suggesting that DM-induced alterations in splenic neutrophils fail to meet the demand in PB and ischemic tissues. Infiltrating macrophages (total, M1, M2) were reduced at day 3 in the DM-ischemic heart, with total and M1 (days 1-3) and M2 (days 3-7) macrophages being significantly decreased in DM-PB compared to controls, indicating impaired macrophage recruitment and polarization in DM. Myeloid dendritic cells (mDCs) in the heart were higher from days 1 to 7, which corresponded with the enhanced recruitment of CD8+ cells from days 1 to 28 in the DM-infarcted myocardium. Total CD4+ cells decreased in DM-PB at days 1 to 3, suggesting a delayed adaptive immune response to MI. B cells were reduced in PB at days 1 to 3, in myocardium at day 3, and in the spleen at day 7, indicating compromised mobilization from BM. EPC-CFA results showed a marked decrease in definitive EPC colonies in the spleen and BM from days 1 to 28 in DM mice compared to controls in vitro, highlighting that DM severely impairs EPC colony-forming activity by limiting the differentiation of EPCs from primitive to definitive forms. Taking together, this study underscores significant disruptions in the cardio-spleen-bone marrow immune cell axis following MI in DM, revealing delayed innate and adaptive immune responses along with impaired EPC differentiation.

Association between stress hyperglycemia ratio and postoperative major adverse cardiovascular and cerebrovascular events in noncardiac surgeries: a large perioperative cohort study

BackgroundThere has been a concerning rise in the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) following noncardiac surgeries (NCS), significantly impacting surgical outcomes and patient prognosis. Glucose metabolism abnormalities induced by stress response under acute medical conditions may be a risk factor for postoperative MACCE. This study aims to explore the association between stress hyperglycemia ratio (SHR) and postoperative MACCE in patients undergoing general anesthesia for NCS.MethodsThere were 12,899 patients in this perioperative cohort study. The primary outcome was MACCE within 30 days postoperatively, defined as angina, acute myocardial infarction, cardiac arrest, arrhythmia, heart failure, stroke, or in-hospital all-cause mortality. Kaplan-Meier curves visualized the cumulative incidence of MACCE. Cox proportional hazard models were utilized to assess the association between the risk of MACCE and different SHR groups. Restricted cubic spline analyses were conducted to explore potential nonlinear relationships. Additionally, exploratory subgroup analyses and sensitivity analyses were performed.ResultsA total of 592 (4.59%) participants experienced MACCE within 30 days after surgery, and 1,045 (8.10%) within 90 days. After adjusting for confounding factors, compared to the SHR T2 group, the risk of MACCE within 30 days after surgery increased by 1.34 times (95% CI 1.08–1.66) in the T3 group and by 1.35 times (95% CI 1.08–1.68) in the T1 group respectively. In the non-diabetes group, the risk of MACCE within 30 days after surgery increased by 1.60 times (95% CI 1.21–2.12) in the T3 group and by 1.61 times (95% CI 1.21–2.14) in the T1 group respectively, while no statistically significant increase in risk was observed in the diabetes group. Similar results were observed within 90 days after surgery in the non-diabetes group. Additionally, a statistically significant U-shaped nonlinear relationship was observed in the non-diabetes group (30 days: P for nonlinear = 0.010; 90 days: P for nonlinear = 0.008).ConclusionIn this large perioperative cohort study, we observed that both higher and lower SHR were associated with an increased risk of MACCE within 30 and 90 days after NCS, especially in patients without diabetes. These findings suggest that SHR potentially plays a key role in stratifying cardiovascular and cerebrovascular risk after NCS.

Beclin1/LC3II/P62 autophagy pathway activation is involved in the protective action of C-peptide against prostate injury in a rat model of type 1 diabetes

One of the undesirable complications of diabetes is sexual dysfunctions in males which may affect their fertility. This research aims to study the effect of C-peptide administration on the prostate of diabetic rats and focusing on exploring the role of the autophagy pathway in diabetic prostate and whether it is involved in C-peptide action. Forty adult male Wistar albino rats were separated into control group, diabetic group, diabetic + C-peptide and diabetic + C-peptide + 3-Methyladenine (autophagy inhibitor). Serum metabolic parameters and prostatic specific antigen (PSA) were measured. Markers of oxidative stress, inflammation, fibrosis, cell proliferation and cell autophagy were evaluated in prostate tissues using biochemical, western blotting and immunohistochemical techniques. C-peptide administration ameliorated the effects of diabetes on the prostate through its hypoglycaemic, antioxidant, anti-inflammatory, and antiproliferative effects which were reversed with autophagy inhibition. Thus, we concluded that C-peptide prevented the effects of diabetes on the prostate through stimulation of the autophagy pathway.

The Effect of Aerial Part of Melissa Officinalis L. Hydro-Alcoholic Extract on Pituitary- Gonadal Axis Function in Diabetic Male Mice

Background: Melissa officinalis L. ( lemon balm) is one of the more widely cultivated medicinal and aromatic plants that has long been used in traditional medicine to treat many disorders. The present study investigates Melissa officinalis L. hydro-alcoholic extract regarding pituitary-gonadal axis in diabetic mice. Methods: 45 NMRI mice with a mean weight of 35.6±4.5 g were divided into five groups: control group (0.2 ml of physiological serum intraperitoneally injection), diabetic mice (without treatment), and three experiment groups (diabetic groups receiving 50, 100 and 200 mg/kg of Melissa officinalis extract intraperitoneally injection). Melissa officinalis extract was injected intraperitoneally for 14 days. At the end of the experiment, blood samples were taken to determine the biochemical indicators level (glucose, LH, FSH, and testosterone), and the left testicle was weighed and examined histologically. Results: The results showed that the lowest amount of glucose and the highest level of LH were observed in the treatment group at a dose of 100 mg/kg of Melissa officinalis extract. The highest level of FSH was observed at a dose of 200 mg/kg. Histological study of the testis showed a more favorable condition in the experimental group of 200 mg/kg of lemon balm extract (P&lt;0.05). Conclusion: It can be concluded that the use of Melissa officinalis extract is efficient in reducing glucose, improving the levels of LH, FSH, and testosterone in diabetic mice, affecting testicular weight, and improving testicular tissue indices and reproductive function of rats.

Assessment of protective effect of Vitamin E supplementation on oxidative damage of diabetic rat spleen induced by Streptozotocin

AimsIncreased oxidative stress in diabetes mellitus may lead to splenic damage, contributing to decreased immunity. This study aims to evaluate the potential of vitamin E supplements as a protective agent against spleen injury by examining physiological, hematological, biochemical, and histological changes in diabetic rat model. MethodsDiabetes was induced in male wistar albino rats through an intraperitoneal injection of 50mg/kg Streptozotocin, and the rats were randomly divided into five groups. The rats were then administered varying doses of vitamin E for 14 consecutive days. Assessments included renal function tests, blood glucose levels, complete blood counts, lipid profiles, tissue oxidative stress and spleen histology. An acute toxicity study was also conducted on normal rats. ResultsVitamin E supplementation did not result in any mortality up to 5000mg/kg body weight. The treated diabetic group showed improved metabolic characteristics, such as normal body weight, food and water intake and a reduced spleen index compared to the untreated diabetic group. Significant improvements were observed in hematological parameters like packed cell volume (PCV), hemoglobin concentration, RBC (red blood cells) and WBC (white blood cells) counts. HCA (Hierarchical Cluster Analysis) of these parameters indicated that doses of 100mg/kg and 150mg/kg were most similar to normal condition. Catalase and MDA (Malondialdehyde) assays showed a substantial reduction in oxidative stress in spleen tissue and histopathological examination revealed significant regenerative effects. ConclusionThis study demonstrated that vitamin E supplementation significantly enhanced various metabolic, hematological, biochemical, and histological parameters in the diabetic group compared to those who did not receive the treatment. Among the doses tested, 100mg/kg and 150mg/kg body weight were found to yield the most favorable outcomes.

“Exploring The Nexus”: Chronic musculoskeletal pain in diabetic vs non-diabetic population

IntroductionDiabetes-mellitus (DM) has transcended the boundaries and affected populations across globe, it predisposes individual to stiffness and musculoskeletal-pain due to accumulation of glycation-end-products. Musculoskeletal-pain is a common yet frequently neglected complication. Pain mechanisms have been categorized as nociceptive, neuropathic, nociplastic, and idiopathic. Four criteria were put by Kosek-et-al to identify nociplastic pain that affects the musculoskeletal-system. Study aimed to evaluate prevalence of chronic musculoskeletal (cMSK) pain and its association with diabetes and glycaemic control and to evaluate comorbid conditions of cMSK pain. Methods and materialsA prospective case-control study was conducted at a level-1-tertiary-care-facility. Patients with type-2 DM above 30-years-age who visited outpatient department participated in the study (study group). Age-matched equal number of healthy individuals (control-cohort) were recruited in the study. We collected data from 300 participants in each group. Analysis was done based-on HbA1c-levels, random-blood-sugar (RBS),clinical-history, and comorbidities. Information regarding cMSK-pain was gathered using modified version of Nordic standard questionnaire. ResultsOverall prevalence of cMSK pain was 23.3 % (140 out of 600). Among Group-1/Diabetic group, it was 27.7 % and among group-2/Healthy Cohort it was 19 % and the odds ratio was 1.6. Most commonly reported region with cMSK among group-1 and group-2 was shoulder (32.5 %) and knee (36.8 %) respectively. We found a significant association between cMSK-pain and HbA1c levels (p < 0.005). and individuals with HbA1c levels of more than 12 reported involvements in multiple regions. We didn't find significant association between cMSK and DM, HTN, dyslipidemia, or hypothyroidism (P > 0.05). ConclusionStudy highlights higher-prevalence and significant impact of cMSK pain in diabetic patients compared to non-diabetic individuals. Addressing musculoskeletal-pain is crucial for improving overall quality-of-life in diabetic patients. Clinicians should adopt a proactive and comprehensive approach to pain management in diabetics. Using a simple Nordic questionnaire during routine check-ups helps with screening of joint and surrounding soft tissue pathology, preventing future complications that could lead to disability.

Agmatine alleviates diabetic-induced hyposalivation in rats: A histological and biochemical study

Diabetic patients commonly experience hyposalivation, which can cause challenges with eating, swallowing, dry mouth, and speaking. It also raises the likelihood of developing periodontal disease. This study aimed to evaluate if agmatine could improve the rate of salivation in rats with hyposalivation induced by streptozotocin (STZ). Five groups of Wistar rats were utilized with 10 animals in each group. They were classified as follows; Negative control group (G1), agmatine (G2) group, and Nicotinamide (NA)-STZ (G3) group; received a single intraperitoneal dose of 65 mg/kg of STZ after NA injection. NA was administered to protect residual β cells and enhance their insulin secretion; NA-STZ + Metformin (G4) Metformin-treated diabetic group; at day 10 diabetic rats received 50mg/kg orally for 28 days, and NA-STZ + Agmatine (G5) at day 10 diabetic rats received a daily intraperitoneal dose of 300 mg/kg Agmatine for 28 days. The salivary flow rate was assessed weekly. Then, the animals were euthanized, both parotid (PG) and submandibular (SMG) salivary glands were dissected, and the following parameters were assessed; salivary glands' histopathology, aquaporin 5 (AQP5), caspase-3, E-cadherin expressions, inflammatory markers and finally, salivary glands' oxidative stress status. Agmatine has alleviated the salivary glands' dysfunction in STZ-induced diabetic rats. It normalized diabetes mellitus-associated salivary glands' abnormalities including histopathological abnormalities, decreased AQP5 and E-cadherin expressions, increased caspase-3 expression, and oxidative stress and inflammatory parameters. Agmatine alleviates diabetes mellitus-associated hyposalivation. It can promote PGs and SMGs function through its histological and AQP5 expression improvements.