Association of systemic immune-inflammation-index with all-cause and cause-specific mortality among type 2 diabetes: a cohort study base on population.

PURPOSE: There have been limited studies examining the prospective association between the Systemic Immune-Inflammation Index (SII), a novel inflammatory marker, and mortality among individuals with diabetes in the United States. METHODS: We utilized data from the National Health and Nutrition Examination Survey (NHANES), a representative sample of US adults, linked with information from the National Death Index. RESULTS: Our study included 8697 individuals from NHANES spanning the years 1999 to 2018. SII was calculated by dividing the platelet count by the neutrophil count and then dividing that result by the lymphocyte count. We employed multivariable Cox proportional hazards regression analysis to investigate the associations between SII levels and all-cause as well as cause-specific mortality, while adjusting for potential confounding factors. SII levels were categorized into quartiles based on the study population distribution. Over a median follow-up period of 94.8 months (with a maximum of 249 months), we observed a total of 2465 all-cause deaths, 853 deaths from cardiovascular causes, 424 deaths from cancer, and 88 deaths related to chronic kidney disease. After adjusting for multiple variables, higher SII levels were significantly and non-linearly associated with an increased risk of all-cause mortality in Quartile 4 (HR 1.74, 95% CI 1.15-2.63, P for trend = 0.043) when Quartile 1 was used as the reference group. Additionally, we identified a linear association between SII and cardiovascular mortality, with a 70% higher risk of cardiovascular mortality in Quartile 4 (HR 1.70, 95% CI 1.18-3.30, P for trend = 0.041) compared to Quartile 1. CONCLUSION: Our findings indicate that SII is significantly associated with an elevated risk of all-cause and cardiovascular mortality in US adults with diabetes.

Modular characteristics and mechanism of action of herbs for type 2 diabetes treatment in Chinese medicine.

Type 2 diabetes (T2D) has emerged as a global epidemic, and conventional treatment approaches often face limitations in achieving long-term glycemic control and preventing complications. Traditional Chinese Medicine (TCM) offers a valuable alternative for managing T2D, with a long history of effectively using herbal formulations in clinical practice. However, the modular characteristics of these herbs and their specific mechanisms of action remain poorly understood. To comprehensively investigate the modular characteristics and mechanisms of Chinese herbs in treating T2D, as well as explore the synergistic interactions among different herbs and their modular components, we employed data mining, systematic pharmacology, and molecular docking. Our aim was to gain a comprehensive understanding of the potential therapeutic targets and pathways involved in herbal T2D treatment. In this study, a total of 1114 studies investigating the effects of TCM interventions in the treatment of T2D in adults were included. The analysis revealed 170 distinct types of Chinese herbs, 118 active components, and 238 common targets shared between the medicine and T2D. Additionally, this study identified six hub proteins (TNF, MMP2, PTGS, CASP3, CASP8, and CASP9) and two key chemicals (Diosgenin and Formononetin) found in TCM-mediated T2D suppression. It was observed that these proteins could bind with the ingredients. The MMP2-Diosgenin interaction exhibited the lowest binding free energy (-13.05 kJ/mol) and was primarily driven by hydrogen bonds with ALA-165. TNF-Diosgenin (-10.5 kcal/mol) showed three hydrogen bonds with LEU-37, ARG-82, and ASN-30. PTGS2 and Diosgenin (-8.71 kJ/mol) demonstrated a hydrogen bond with HIS-214. Furthermore, CASP9-Formononetin (-6.53 kcal/mol) exhibited the lowest binding free energy and hydrogen bonds with GLU-261 and SER-339 as the primary forces involved. CASP3-Formononetin (-6.07 kcal/mol) displayed three hydrogen bonds with ASN-342, TRP-348, and GLU-379. Lastly, CASP8 and Formononetin (-6.06 kJ/mol) formed a hydrogen bond with THR-390, TYR-392, and TYR-334. Moreover, critical therapeutic pathways, such as the immune inflammatory response, AGE-RAGE, and IL-17 signaling pathway, were found to be associated with T2D Chinese herb therapy. In conclusion, this study sheded light on the modular characteristics and mechanism of action of herbs used in Chinese Medicine for the treatment of T2D, which provided valuable insights for both researchers and practitioners in the field of Chinese Medicine, offering potential avenues for improved treatment strategies and personalized approaches to address the complex nature of T2D.

The protective role of shenqi compound in type 2 diabetes: A comprehensive investigation of pancreatic ß-cell function and mass.

Type 2 diabetes (T2D) is a prevalent metabolic disorder characterized by impaired insulin secretion and insulin resistance, resulting in elevated blood glucose levels. The dysfunction and loss of pancreatic ß-cells, responsible for producing insulin, contribute to the development of T2D. Traditional Chinese medicine (TCM) has emerged as a potential source of innovative therapeutic interventions. However, limited research exists on Chinese herbal formulations specifically targeting the protection of pancreatic ß-cell function and mass. One such formulation is the Shenqi compound (SQC), widely used in China and consisting of Panax Ginseng, Astragali Radix, Rhizoma Dioscoreae, Corni Fructus, Rehmanniae Radix, Salviae Miltiorrhizae Radix et Rhizoma, Radix Trichosanthis, and Rhei Radix et Rhizoma. Understanding the mechanisms underlying the therapeutic effects of SQC is crucial for developing novel treatment strategies for T2D. This study aims to comprehensively investigate the scientific evidence supporting the role of SQC in alleviating T2D by targeting the protection of pancreatic ß-cell function and mass. Spontaneously diabetic GK rats were used as the animal model, receiving SQC (14.4 g/kg/d) for 8 weeks. The results demonstrate multiple beneficial effects of SQC, including significant control of blood glucose levels (P < 0.05), inhibition of insulin resistance (measured by Western Blot), reduction of hyperinsulinemia (P < 0.05), attenuation of oxidative stress (P < 0.05), suppression of inflammation (P < 0.05), protection against islet hypertrophy and beta cell proliferation (evaluated through pathological staining), and inhibition of ß-cell apoptosis and senescence (also assessed through pathological staining). These findings indicate the promotion of ß-cell survival and function. In vitro experiments using isolated islets further support these results, revealing improvements in insulin secretion (P < 0.05) and ß-cell function following SQC therapy (P < 0.05). This represents a significant breakthrough in addressing ß-cell dysfunction and preserving mass within the context of TCM. Overall, SQC shows promise as a natural therapeutic approach for T2D, with potential benefits in preserving pancreatic ß-cell function and mass. This enhances the practical applicability and significance of the research by bridging the gap between experimental findings and clinical practice, thereby providing important clinical value in TCM treatment of T2D. Further research is necessary to elucidate its precise mechanisms of action and optimize its clinical application.

Associations of composite dietary antioxidant index with cardiovascular disease mortality among patients with type 2 diabetes.

To investigate the associations of composite dietary antioxidant index (CDAI) with risk of cardiovascular disease (CVD) mortality among individuals with type 2 diabetes (T2D). This prospective cohort study included 7551 patients with T2D who participated in the National Health and Nutrition Examination Survey (NHANES) from 1999 through 2018. Death statistics were gathered by connecting the cohort database to the National Death Index through December 31, 2019. Multivariable Cox proportional hazards regression models were utilized to calculate hazard ratios and 95% CIs for the relationship of CDAI with risks of CVD and all-cause mortality. Three multivariable models were built. Restricted cubic spline analyses were utilized to explore the nonlinear association of CDAI with CVD mortality, and nonlinearity was tested by the likelihood ratio test. This cohort study included data from 7551 participants with T2D (mean [SE] age, 61.4 (0.2) years; 3811 male [weighted, 50.5%] and 3740 female [weighted, 49.5%]; median CDAI level, - 2.19 [IQR, - 2.19 ~ - 0.22]). A total of 2227 all-cause deaths and 746 CVD deaths were identified during an average of 98 months of follow-up. Nonlinear associations were observed for CDAI (P < 0.05 for nonlinearity) with risk of CVD mortality among patients with T2D. Compared with participants in the first quartile of CDAI levels (< - 2.19), the hazard ratios for CVD mortality were 0.47 (95% CI 0.30-0.75) for participants in the highest CDAI level quartile. This cohort study found that higher CDAI levels were significantly associated with lower risk of CVD mortality among individuals with T2D.

Key circRNAs, lncRNAs, and mRNAs of ShenQi Compound in Protecting Vascular Endothelial Cells From High Glucose Identified by Whole Transcriptome Sequencing.

ABSTRACT: Vascular endothelial cells, which make up the inner wall of blood arteries, are susceptible to damage from oxidative stress and apoptosis caused by hyperglycemia. According to certain reports, noncoding RNAs are involved in controlling oxidative stress and apoptosis. ShenQi Compound (SQC), a traditional herbal remedy, has been successfully treating diabetic vascular disease in China for more than 20 years. Although it is well established that SQC protects the vascular endothelium, the molecular mechanism remains unknown. Goto-Kakizaki rats, spontaneous type II diabetes rats, that consistently consume a high-fat diet were chosen as model animals. Six groups (control group, model group, metformin group, and 7.2 g/kg/d SQC group, 14.4 g/kg/d SQC group, and 28.8 g/kg/d SQC group) were included in this work, 15 rats each group. The approach of administration was gavage, and the same volume (5.0 mL/kg/d) was given in each group, once a day, 12 weeks. The thoracic aortas were removed after the rats were sacrificed. Oxidative reduction profile in thoracic aorta, histopathological observation of thoracic aorta, endothelial cell apoptosis in thoracic aorta, whole transcriptome sequencing, bioinformatic analyses, and qRT-PCR were conducted. As a result, SQC prevented the oxidative stress and apoptosis induced by a high glucose concentration. Under hyperglycemia condition, noncoding RNAs, including 1 downregulated novel circRNA (circRNA.3121), 3 downregulated lncRNAs (Skil.cSep08, Shawso.aSep08-unspliced, and MSTRG.164.2), and 1 upregulated mRNA (Pcdh17), were clearly reverse regulated by SQC. SQC plays a role in protecting vascular endothelial cells from high glucose mainly by mediating ncRNA to inhibit cell apoptosis and oxidative stress.

Characterization of lncRNA and mRNA profiles in rats with diabetic macroangiopathy.

Diabetic macroangiopathy is part of the most common serious complications of diabetes. Previous studies indicate that lncRNAs involved in the process of diabetes and another vascular disease. However, their detailed mechanism of the lncRNAs involved in diabetic macroangiopathy has not been well characterized. In the present study, we generated rat models of diabetic macroangiopathy induced by High fat of 16weeks. A total of 15 GK rats were constructed as a test group, along with 15 Wistar rats set as control group, and thoracic aorta tissue from each group was collected. Whole genomic RNA sequencing was performed on thoracic aorta tissue; 3223 novel lncRNAs and 20367 annotated lncRNAs were indemnified in thoracic aorta samples, and 864 lncRNAs were expressed differently in the test and control groups. Gene ontology term enrichment showed the apparent enrichment of inflammatory response and cell apoptosis, which consistent with the results of H&E Staining, TUNEL Assay, and ELISA; Extensive literature reveals inflammatory response and cell apoptosis play an important role in the process of diabetic macroangiopathy. The results of the present study indicated that lncRNAs, especially Nrep. bSep08, Col5a1, aSep0, soygee.aSep08-unspliced, NONRATT013247.2, votar.aSep08-unspliced, etc, both participate in and mediate the process of inflammatory response, cell apoptosis. What's more. Our research provides further insights into understanding of the basic molecular mechanisms underlying diabetic macroangiopathy.