The shape of the oral glucose tolerance test (OGTT) curve is an early predictor of metabolic disturbances. In this study, we analyzed which parameters are associated with different OGTT-curve shapes (CS) in healthy middle-aged and older adults.

In the cross-sectional Enable Study, 354 participants were comprehensively phenotyped. Based on a 2-hour OGTT, CS was classified according to the presence (polyphasic) or absence (monophasic, mp) of a rise in plasma glucose of more than 4.5 mg/dL after the first decline of the plasma glucose level. Associations between CS and age, sex, anthropometric, metabolic, and inflammatory parameters were analyzed by binomial logistic regression.

Curve shape was mp in 77.4% of the participants without age group difference, but a higher frequency was observed in men (89.3%) compared to women (65.5%, P < .001). The odds of mp CS increased with higher fasting GLP-1 (odds ratio [OR], 1.066; 95% CI, 1.006-1.133; P < .05) and 1-hour plasma glucose (OR, 1.054; 95% CI, 1.037-1.072; P < .001) and lower 2-hour plasma glucose (OR, 0.975; 95% CI, 0.959-0.992; P < .01).

In healthy adults, mp CS was widespread and associated with more unfavorable metabolic parameters. A higher fasting GLP-1 level was associated with an mp CS.

Chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) are on the rise. While there is evidence of a link between the two diseases, the pathophysiological mechanisms they share are not fully understood.

In this study, the co-expressed genes of COPD and T2DM in Gene Expression Omnibus database were identified by bioinformatics method, and the functional enrichment analysis was performed. Machine learning algorithms were used to identify biomarkers. The diagnostic value of these biomarkers was assessed by receiver operating characteristic analysis, and their relationship to immune cells was investigated by immunoinfiltration analysis. Finally, real-time quantitative polymerase chain reaction was performed.

A total of five overlapping genes were obtained, focusing on pathways associated with insulin resistance and inflammatory mediators. The machine learning method identified three biomarkers: matrix metalloproteinase 9, laminin α4, and differentially expressed in normal cells and neoplasia domain containing 4 C, all of which were shown to have high diagnostic values by receiver operating characteristic analysis. Immunoinfiltration analysis showed that it was associated with a variety of immune cells. In addition, the real-time quantitative polymerase chain reaction results confirmed agreement with our bioinformatics analysis.

Our study sheds light on the common pathogenesis and biomarkers of both diseases, and these findings have potential implications for the development of new diagnostic and treatment strategies for COPD and T2DM. Key message What is already known on this topic?  Chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) often coexist as comorbidities. However, the exact mechanistic link between the two diseases remains complex, multifactorial, and not fully understood. What this study adds?  Three biomarkers, including matrix metalloproteinase, laminin α4, and differentially expressed in normal cells and neoplasia domain containing 4 C, were identified as key co-expression hub genes in COPD and T2DM. How this study might affect research, practice or policy?  Future studies may benefit from incorporating a larger sample set to further explore and validate the diagnostic and therapeutic effects of these core genes.

Type 2 diabetes (T2D) is consistently related to an increased risk of cognitive decline and dementia. However, the molecular underpinnings of this association remain poorly understood. In this study, we applied a novel mass spectrometry-based glycoproteomic methodology to profile serum glycoproteins in older adults with T2D, aiming to identify glycopeptiforms associated with cognitive impairment. Our method allowed comprehensive profiling of N glycosylation in addition to the unique ability to profile glycation events on specific amino acid sites. Serum samples from initially cognitively normal older adults with T2D were collected, with participants classified as cognitive decliners (who developed impairment) and non-decliners (who maintained normal cognition over time). We identified significant differences in the abundance of glycopeptiforms between these groups, noting that certain glycopeptiforms exhibited unique changes over time in decliners. We identified 13 glycopeptiforms that exhibited significant differences between the groups both at baseline and in their rates of change over time. Pathway analysis indicated that glycation events were linked to metabolic pathways while glycosylation to immune-related pathways, aligning with established links between these processes and cognitive decline. This study offers new insights into glycoproteoform alterations in older adults with T2D experiencing cognitive decline. It highlights the potential of specific glycopeptiforms as biomarkers for early cognitive impairment in T2D. Further validation in larger cohorts will enhance our understanding of glycosylation and glycation in T2D and potentially lead to the discovery of novel treatment targets for T2D-related cognitive decline. Raw data and search are available via ProteomeXchange with identifier PXD050780.

The increase in sugar consumption has been associated with current metabolic disease epidemics. This study aimed to investigate the pancreatic molecular mechanisms involved in cellular stress, inflammation, mitogenesis, and apoptosis in metabolic disease induced by high-fructose diet. Here, we used biochemical, histopathological, Western blot, and immunohistochemistry methods to determine the metabolic and pancreatic alterations in male Wistar rats fed 20% fructose in drinking water for 15 weeks. High-fructose consumption in rats increased the immunopositivity and protein expression of glucose transporter 2 (GLUT2) and insulin in the pancreatic tissue, in association with abdominal adiposity, hyperglycemia, and hypertriglyceridemia. The expressions of cellular stress markers, glucose-regulated protein-78 (GRP78) and PTEN-induced putative kinase 1 (PINK1), were increased in the pancreas. The levels of interleukin (IL)-6, nuclear factor kappa B (NFκB), tumor necrosis factor α (TNFα), and IL-1β and components of the Nod-like receptor protein 3 (NLRP3) inflammasome were elevated. Excess fructose intake stimulated the activation of mitogenic extracellular signal-regulated kinases 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase (JNK)1 as well as the apoptotic p53 and Fas pathways in the pancreas of rats. There was also an increase in caspase-8 and caspase-3 cleavage. Our findings revealed that dietary high-fructose in the pancreas causes hyperinsulinemia due to the upregulation of GLUT2 together with cellular stress and inflammatory markers, thereby stimulates mitogenic mitogen-activated protein kinase (MAPK) and apoptosis pathways, resulting in a complex pathological situation.

In recent years, the prevalence of metabolic diseases has increased significantly, posing a serious threat to global health. Chronic low-grade inflammation is implicated in the development of most metabolic diseases, such as type 2 diabetes mellitus (T2DM), obesity, dyslipidemia, and cardiovascular disease, serving as a link between diet and these conditions. Increasing attention has been directly toward dietary inflammatory patterns that may prevent or ameliorate metabolic diseases. The Dietary Inflammatory Index (DII) was developed to assess the inflammatory potential of dietary intake. Consequently, a growing body of research has examined the associations between the DII and the risk of several metabolic diseases. In this review, we explore the current scientific literature on the relationships between the DII, T2DM, obesity, and dyslipidemia. It summarizes recent findings and explore potential underlying mechanisms from two aspects: the interaction between diet and inflammation, and the link between inflammation and metabolic diseases. Furthermore, this review discusses the therapeutic strategies, including dietary modifications, prebiotics, and probiotics, and discusses the application of the DII in metabolic diseases, as well as future research directions.

Arecoline, the main alkaloid in areca nut, has shown potential in modulating metabolism and gut microbiota. This study aimed to evaluate its therapeutic effects on glucose and lipid metabolism, inflammation, liver function, and potential mechanisms in a Type 2 diabetes mellitus (T2DM) mouse model.

T2DM was established in mice with a high-fat, high-sugar diet, and streptozotocin injections. Arecoline significantly reduced fasting blood glucose, enhanced glucose tolerance, and increased insulin sensitivity. Serum lipid profiles showed marked decreases in total cholesterol, triglycerides, and LDL-C levels. Systemic inflammation, as measured by serum levels of IL-1β, IL-6, and MCP-1, decreased significantly. Improvements in liver function were observed, as indicated by reductions in ALT and AST levels. Liver transcriptomic analysis revealed modulation of pathways related to glutathione metabolism, MAPK signaling, and cAMP signaling, which were involved in insulin signaling and oxidative stress response. Additionally, arecoline mitigated gut dysbiosis by restoring microbial diversity, altering gut microbiota composition, and regulating key pathways involved in NAD biosynthesis and fatty acid β-oxidation, which were critical for maintaining energy homeostasis.

Arecoline improves glucose metabolism, lipid profiles, and liver function, while modulating gut microbiota and liver metabolic pathways, showing potential as a therapeutic agent for T2DM.

Background: Firefighters are at risk for developing metabolic diseases such as type 2 diabetes due to occupational-related stress and poor health behaviors. Firefighters often experience chronic inflammatory responses that may contribute to the development of insulin resistance. This study examined the relationship between systemic inflammation markers and glycemic control markers in firefighters. Methods: Blood samples were collected from twenty full-time male firefighters to assess HbA1c, fasting glucose, and insulin to estimate the Homeostatic Model of Assessment of Insulin Resistance (HOMA-IR), C-reactive protein (CRP), and homocysteine. Body composition and cardiovascular metrics were also recorded. Pearson partial correlation analyses were performed to evaluate relationships between homocysteine and CRP and the variables HOMA-IR and HbA1c while controlling for age and body fat percentage (BF%). SPSS version 29 was used for all analyses (α = 0.05). Data transformation was used where appropriate to ensure the normal distribution of each variable. Results: A significant positive correlation was found between homocysteine and HbA1c before (p = 0.006, r = 0.605) and after controlling for age and BF% (ppartial = 0.013, rpartial = 0.588), indicating that homocysteine levels are associated with impaired glycemic control in firefighters. No other relationships were found to be significant. Conclusions: The findings support a potential link between systemic inflammation and poor glycemic control in firefighters. Due to the occupational hazards that contribute to chronic inflammation, targeted interventions such as dietary modifications may help decrease the risk of diabetes and cardiovascular disease in this high-risk population.

Obesity is a systemic, chronic, low-grade inflammatory disease. Nutritional obesity, in particular, is also accompanied by inflammation and metabolic disorders, which are the primary causes of malignant metabolic diseases. Rhizoma Coptidis (Coptis Chinensis Franch) (RC), a traditional Chinese medicine, is primarily used for its anti-inflammatory and anti-diarrheal properties. Our previous studies have shown that RC can reduce body weight and lower fat levels, demonstrating its potential to improve nutritional obesity.However, the effects and mechanisms of the active small molecules in RC extracts in treating obesity-induced chronic inflammation need to be further investigated. In this study, we investigated the ameliorative effect and mechanism study of the monomeric jatrorrhizine (JAT) extracted from RC on high-fat diet-induced obese mice. First, JAT could dose-dependently reduce body weight and decrease the expression of inflammatory factors such as IL6, IL1β, and TNFα in the tissues of obese mice.Secondly, transcriptomics and bioinformatics studies of epididymal white adipose tissue (eWAT) identified Mmp12 as a key target through which JAT may alleviate obesity. Next, the effect of JAT on c-Jun/c-Fos promoter activity, which in turn down-regulates the transcript and protein levels of Mmp12, was analyzed and determined by qPCR, transcription factor prediction, single fluorescent promoter activity assay, Cell thermodynamic stability analysis (CETSA), molecular dynamics simulation mimicry, circular dichroism (CD) and Co-Immunoprecipitation (Co-IP). In conclusion, JAT may ameliorate high-fat diet-induced obesity and its associated inflammation through the c-Jun/c-Fos-Mmp12 axis.

Diabetic peripheral neuropathy (DPN) is a serious complication of diabetes mellitus, which is a common cause of disability in individuals with diabetes mellitus. Multiple mechanisms may be involved in the development of DPN. Neuroinflammation is a critical factor contributing to nerve damage during diabetes. Inflammation can induce the development of diabetes mellitus, and long-term hyperglycemia also causes increased oxidative stress and promotes the release of inflammatory cytokines. After reading through the literature, the association of inflammation with the induction of diabetes and DPN was discussed in the review. Inflammation induces nerve damage and nerve conduction impairment. The neuropathic pain in diabetes-induced DPN is also closely associated with the inflammatory response. Given the important roles of inflammation in diabetes-induced DPN, explicit elucidation of neuroinflammation during diabetes mellitus and DPN should hold the potential for developing novel therapeutic strategies for DPN. Experimental studies and limited clinical trials support the value of anti-inflammatory reagents in treating DPN, and the positive outcomes of these investigations warrant further clinical trials.

Longitudinal studies now document how leukocyte telomere attrition and epigenetic aging may be accelerated in people with HIV (PWH), in particular, around the time of HIV acquisition, during primary HIV infection, and during untreated chronic HIV infection. Whether chronic low-level inflammation and epigenetic aging go hand in hand or may be partially independent continues to be investigated in PWH and other settings. Epigenetic age acceleration (EAA) in PWH has now clearly been shown to be potentially reversible during successful antiretroviral therapy (ART). These studies point to how the beneficial effects of modern ART also include EAA-decelerating effects that seem large enough to regard ART as a kind of epigenetic rejuvenation therapy. Progress in the field has been limited in part due to the high cost of assessing EAA based on DNA methylation measures ("epigenetic clocks"). Demonstration of the clinical relevance of EAA and its reversion by ART will depend on large studies associating EAA with cardiovascular events and other adverse aging-associated endpoints in PWH.

To investigate whether the antidiabetic agent glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can exert anti-inflammatory effects while lowering blood glucose, we performed a meta-analysis and systematic review.

We searched 4 online databases (Medline, Embase, Cochrane Library and the Web of Science) for randomised controlled trials (RCTs) that examined changes after GLP-1RAs intervention in commonly accepted biomarkers of inflammation: C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), leptin, adiponectin, plasminogen activator inhibitor-1 (PAI-1), monocyte chemotactic protein-1(MCP-1) and advanced glycation end products (AGEs).

This meta-analysis included 52 eligible RCTs (n = 4734) with a median follow-up of 24 weeks, a mean age of 54.13 years, 44.46% females, body mass index (BMI) 29.80 kg/m2, glycated haemoglobin (HbA1c) 8.28% and diabetes duration 7.27 years. GLP-1 RAs treatment, compared to placebo or conventional diabetes therapies (including oral medicine and insulin), resulted in significant reductions in CRP, TNF-α, IL-6, IL-1β and leptin (standard mean difference [SMD] -0.63 [-1.03, -0.23]; SMD -0.92 [-1.57, -0.27]; SMD -0.76 [-1.32, -0.20], SMD -3.89 [-6.56, -1.22], SMD -0.67 [-1.09, -0.26], respectively), as well as significant increases in adiponectin (SMD 0.69 [0.19, 1.19]).

Our meta-analysis demonstrates that GLP-1 RAs exert significant anti-inflammatory effects in patients with T2DM. Our findings provide important insights that may guide the therapeutic application of GLP-1 RAs and inform the development of related therapies.

Sotagliflozin, a dual SGLT1/2 inhibitor, enhances glucagon like peptide-1 (GLP-1) levels and GLP-1 receptor agonists are used to manage non-alcoholic fatty liver disease (NAFLD). Study investigates the effects of sotagliflozin on NAFLD, alone and combined with linagliptin, comparing outcomes in normoglycemic and hyperglycemic animal models.Obese fatty liver disease (FLD) model was induced by high-fat diet (HFD) feeding, while a diabetic non-alcoholic steatohepatitis (NASH) model was developed by administering a single dose of streptozotocin to neonatal mice, followed by HFD feeding post-weaning. At termination of the study, parameters including biochemical markers, inflammatory cytokines, hepatic lipid content, and histopathology were assessed.In NASH mice, sotagliflozin and linagliptin reduced hepatic triglycerides by 60% and 44%, respectively, and cholesterol by 46% and 49%. Their combination further decreased triglycerides by 68.5% and cholesterol by 83.9%. In FLD mice, sotagliflozin and linagliptin reduced triglycerides by 33% and 17%, respectively, and cholesterol by 46% and 21%. Combination treatment offered no benefit, reducing triglycerides by 38% and cholesterol by 27%. Both the treatments improved plasma fibroblast growth factor 21, hepatic interlukin-6, glucose tolerance, steatosis and mitigated fat pad weight, but their combination did not show additional benefit. However, combination treatment demonstrated added benefit in modulating NAFLD activity score, liver enzymes, glycogenated hepatic nuclei, plasma glucose and active GLP-1 levels.Study underscores sotagliflozin's potential to mitigate NAFLD and highlights the benefit of combining it with linagliptin in hyperglycemic NASH model, which showed limited efficacy in normoglycemic FLD mice.

In recent years, therapeutic approaches against diabetes-induced liver damage have attracted great interest. Studies indicate the anticarcinogenic, anti-inflammatory, antioxidant, and lipid-lowering potential of hesperidin (HESP), a flavonoid in citrus fruits. This study examined how HESP prevented streptozotocin (STZ)-induced diabetic liver damage. Four groups of seven rats each were created: Control, HESP (100 mg/kg/day), STZ (45 mg/kg), and STZ + HESP (45 mg/kg and 100 mg/kg/day, respectively). Serum AST, ALT, LDH, LDL, triglyceride, total cholesterol levels, and the TNF-α, IL-1β, and caspase-3 expression levels of liver tissue in the STZ group were higher than the other groups (p < 0.05). However, these values were significantly lower (p < 0.05) in the STZ + HESP group compared to the STZ group. Furthermore, administering HESP together with STZ reduced liver expression levels of caspase-3, TNF-α, and IL-1β, as well as blood levels of AST, ALT, LDH, LDL, triglyceride, and total cholesterol. HESP against diabetes-induced hepatic damage reduced proinflammatory cytokine levels, and returned the lipid profile, and apoptotic indicators to normal levels. These findings suggested that HESP therapy may be an important therapeutic role against diabetes-induced liver damage.

This study evaluated the predictive value of the APF risk score in East Asian patients undergoing open nephrectomy and its correlation with hypertension and NAFLD.

A retrospective study used the clinical data of 82 patients who underwent ON between January 2010 and December 2022. Per their APF score, patients were categorized into groups A (0-2 points) and B (3-4 points). Logistic regression analyses were used to compare the overall clinical data between the two groups and identify potential risk factors. Intraoperative APF prevalence was significantly higher in group B compared to group A (P < 0.001). Group B patients were older (63.06 ± 8.88 vs. 53.69 ± 15.21 years) and had higher incidences of hypertension (P < 0.001), diabetes (P = 0.002), and NAFLD (P < 0.001). Preoperative CT scans showed significant differences in posterior (P = 0.009) and lateral perinephric fat thickness (P < 0.001), and perinephric stranding (P < 0.001). Group B also had a higher proportion of malignant tumors (P = 0.039). Multivariate logistic regression revealed that NAFLD (OR = 9.053, P = 0.010) and hypertension (OR = 5.181, P = 0.025) were highly correlated with APF risk scores.

In this study, we found that the newly developed APF risk score had significant value in predicting APF in East Asian patients undergoing open nephrectomy. Additionally, NAFLD and hypertension were highly correlated with elevated APF risk scores.

Postprandial hyperglycemia induces expression of inflammatory cytokines including tumor necrosis factor (TNF), which promotes the onset of type 2 diabetes and cardiovascular diseases. In this study, we investigated whether a transient high-glucose culture enhanced sustained expression of TNF, or whether the induction is associated with histone acetylation, and bromodomain protein containing protein 4 (BRD4), which binds acetylated histone, in human juvenile macrophage-like THP-1 cells.

THP-1 cells were cultured in medium with high-glucose in the presence or absence of (+)-JQ1, an inhibitor of bromodomain and extra-terminal domain family, for 24 h (day 0). Thereafter, the cells were returned to a low-glucose medium without (+)-JQ1 and cultured for 2 or 4 days and samples were collected. mRNA expression of inflammation genes, and histone H3 K9/14 acetylation and binding of BRD4 and RNA polymerase II around the TNF gene were measured by RT-qPCR and chromatin immunoprecipitation, respectively.

TNF mRNA levels, histone H3 K9/14 acetylation, and bindings of BRD4 and RNA polymerase II to the TNF gene were higher in cells exposed to high-glucose culture for 24 h and subsequently cultured in low-glucose medium for 2-4 days, compared with cells cultured in a low-glucose medium. The addition of (+)-JQ1 to the high-glucose medium for 24 h reduced histone H3 K9/14 acetylation, and BRD4 and RNA polymerase II bindings around TNF gene, and the mRNA levels.

Histone H3 K9/14 acetylation and BRD4 binding are associated with the sustained expression of TNF mRNA induced by temporal high-glucose exposure in juvenile macrophage-like THP-1 cells.

Anemia is a frequent, yet increasingly recognized, comorbidity in diabetes mellitus (DM), with prevalence often driven by multifactorial mechanisms. Hematinic deficiencies, common in this population, may arise from associated comorbidities or medications, such as metformin, as well as other drugs commonly employed for DM-related conditions. Among contributing factors, diabetic kidney disease (DKD) plays a pivotal role, with anemia developing more frequently and being more pronounced in earlier stages, than in CKD of other causes. This enhanced susceptibility stems primarily from the combined impact of impaired renal oxygen sensing and deficient erythropoietin (EPO) production linked to tubulointerstitial fibrosis. Additional mechanisms comprise glomerular dysfunction, shortened erythrocyte lifespan, uremia-induced bone marrow suppression, and increased bleeding risk. DM is also recognized as a chronic low-grade inflammatory condition, with its inflammatory burden driving iron maldistribution, suppression of erythropoiesis, and resistance to EPO. The diagnostic approach of anemia in DM mirrors that in the general population. Addressing modifiable causes such as hematinic deficiencies, and other chronic conditions, such as DKD and bone marrow disorders, is paramount. In total, the underlying pathophysiology of anemia in DM primarily reflects a state of absolute or relative EPO deficiency and/or diminished bone marrow responsiveness, effectively corresponding to 'anemia of chronic disease. Early initiation of EPO therapy, even in DM patients without overt DKD, may mitigate disease progression and improve outcomes. Future research should focus on diabetes-specific strategies integrating optimal EPO use, potentially implementing targeted management of renal and inflammatory contributors to anemia.

The nutritional status of communities susceptible to Buruli ulcer (BU, a skin NTD caused by infection with Mycobacterium ulcerans) remains almost completely obscure. We have assessed the diets of BU patients vs. controls from the same BU-endemic communities, and compared their circulating biomarkers of nutrients and inflammation.

We investigated two cohorts of BU patients and controls. The first were administered food frequency and multi-pass 24-hour recall questionnaires to determine patterns of foods consumed, nutrient intake and nutrient adequacy. The second used archived serum samples collected as baseline to measure the circulating concentration of zinc, vitamin C, CRP, IL-1β, IFN-γ, TNF-α and IL-6. Stunted growth was more prevalent than expected (31%), while 18% of participants were underweight and most had inadequate intake of all micronutrients except for carbohydrate. BU patients had a lower intake of, selenium, vitamin B12 and zinc, and for selenium and vitamin B12 a higher proportion had dietary insufficiency (40% vs. 15% and 80% vs. 55%, respectively). In line with this, BU patients had significantly lower levels of zinc in their serum, and more had levels below the normal range (72% vs. 43%). Despite many participants having a good intake of vitamin C, serum levels were low, and lower amongst the BU patients. As expected, there was little evidence of systemic inflammation (CRP <0.6 mg/L). Elevated IL-6 levels were present in several participants suggesting that environmental enteric dysfunction may be prevalent in these communities, however this was similar in cases vs. controls.

Diet and nutritional status may be a contributing factor to BU pathogenesis. Protein and the micronutrients zinc, selenium, vitamin B12 and vitamin C may be of particular importance. Nutritional interventions may have potential for both prophylaxis and treatment of BU, which may be a cost-effective approach to achieving the NTD Roadmap goals.

The amazing diversity of B cells within the tumor microenvironment is the basis for the diverse development of B cell-based immunotherapies. Here, we focus on elucidating the mechanisms of tumor intervention mediated by four tumor-infiltrating B lymphocytes. Naive B cells present the initial antigen, germinal center B cell subsets enhance antibody affinity, and immunoglobulin subtypes exert multiple immune effects, while regulatory B cells establish immune tolerance. Together they reflect the complexity of the changing dynamics of cancer immunity. Additionally, we have investigated the dynamic effects of tumor-infiltrating B lymphocytes in immunotherapy and their relationship to prognosis, providing new insights into potential treatment strategies for patients.

Background: Polysaccharides produced by the edible fungus Cordyceps cicadae can regulate blood sugar levels and may represent a suitable candidate for the treatment of diabetes and its complications. However, there is limited information available about the mechanism of how C. cicadae polysaccharide (CCP) might improve diabetic conditions. Methods: This study investigated its effects on the intestinal microbiota, intestinal mucosal barrier, and inflammation in mice with type 2 diabetes mellitus (T2DM) induced by streptozotocin, and its potential mechanisms. Results: Compared with the DC (diabetes model control group), CCPH oral treatment significantly increased the number of beneficial bifidobacteria, bifidobacteria, and lactobacilli (p < 0.01), restored the diversity of intestinal microorganisms in diabetic mice, and the proportions of Firmicutes and Bacteroidetes (34.36%/54.65%) were significantly lower than those of the DC (52.15%/32.09%). Moreover, CCPH significantly reduced the content of endotoxin (lipopolysaccharide, LPS) and D-lactic acid(D-LA) (p < 0.05), the activities of antioxidant enzymes and total antioxidant capacity were significantly increased (p < 0.01), and the content of proinflammatory cytokines TNF-α, IL-6, and IL-1β were reduced by 42.05%, 51.28%, and 52.79%, respectively, compared with the DC. The TLR4/NF-κB signaling pathway, as a therapeutic target for diabetic intestinal diseases, plays a role in regulating the inflammatory response and protecting the intestinal barrier function. Molecular mechanism studies showed that oral treatment with CCPH down-regulated the expression of NF-κB, TLR-4, and TNF-α genes by 18.66%, 21.58%, and 34.87%, respectively, while up-regulating the expression of ZO-1 and occludin genes by 32.70% and 25.11%, respectively. CCPH regulates the expression of short-chain fatty acid levels, increases microbial diversity, and ameliorates mouse colon lesions by inhibiting the TLR4/NF-κB signaling pathway. Conclusions: In conclusion, it is demonstrated that in this murine model, the treatment of diabetes with C. cicadae polysaccharide can effectively regulate intestinal microbiota imbalance, protect intestinal mucosal barrier function, and reduce inflammation in vivo, suggesting this natural product can provide a suitable strategy for the treatment of T2D-induced gut dysbiosis and intestinal health.

Circadian rhythms have evolved to synchronize gene expression, physiology, and behavior with time-of-day changes in the external environment. In every mammalian cell exists a core clock mechanism that consists of a transcriptional-translational feedback loop that drives rhythmic gene expression. Circadian disruption, as observed in shift workers and genetic mouse models, contributes to the onset and progression of cardiometabolic disorders. The central clock, located in the hypothalamus, is uniquely sensitive to external light cues, while the peripheral clocks are responsive to non-photic stimuli such as feeding and activity in addition to signals from the central clock. Recent research has illustrated the sensitivity of the skeletal muscle circadian clock to exercise timing, offering a promising avenue for therapeutic intervention in cardiometabolic health. Here we provide an in-depth examination of the molecular mechanisms underlying skeletal muscle clock function and its impact on cardiometabolic pathways, including glucose and lipid metabolism, as well as inflammation. To highlight the role of exercise as a time-cue for the skeletal muscle clock, we discuss evidence of exercise-induced shifts in the skeletal muscle clock and the differential response to exercise performed at different times of the day. Furthermore, we present data in support of time-of-day exercise as a potential therapeutic strategy for mitigating cardiometabolic disease burden. By exploring the relationship between the skeletal muscle clock, exercise timing, and cardiometabolic health, we identify new areas for future research and offer valuable insights into novel therapeutic approaches aimed at improving cardiometabolic disease outcomes.

Increased activity of the NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome-IL-1β pathway is observed in obesity and contributes to the development of type 2 diabetes and its complications. In this review, we describe the pathological activation of IL-1β by metabolic stress, ageing and the microbiome and present data on the role of IL-1β in metabolism. We explore the physiological role of the IL-1β pathway in insulin secretion and the relationship between circulating levels of IL-1β and the development of diabetes and associated diseases. We highlight the paradoxical nature of IL-1β as both a friend and a foe in glucose regulation and provide details on clinical translation, including the glucose-lowering effects of IL-1 antagonism and its impact on disease modification. We also discuss the potential role of IL-1β in obesity, Alzheimer's disease, fatigue, gonadal dysfunction and related disorders such as rheumatoid arthritis and gout. Finally, we address the safety of NLRP3 inhibition and IL-1 antagonists and the prospect of using this therapeutic approach for the treatment of type 2 diabetes and its comorbidities.

Hidradenitis suppurativa (HS) is associated with an increased prevalence of cardiovascular diseases compared with the general population. Any association between polygenic risk for HS, risk of incident cardiometabolic outcomes, and the plasma proteome is unclear.

To investigate the genetic correlation between HS and cardiometabolic disease.

This cohort study used a polygenic risk score (PRS) for HS to examine the risks of coronary artery disease (CAD) and diabetes and identify changes in the plasma proteome in individuals of European ancestry from the UK Biobank. Participants were enrolled from January 1, 2006, to December 31, 2010. End of follow-up was January 1, 2023. Correlations were assessed between HS susceptibility and cardiometabolic traits using linkage disequilibrium score regression. Odds ratios were assessed in logistic regressions. The risk of incident CAD and diabetes was estimated in cause-specific survival models designed as time-to-event analyses.

The PRS for HS.

Main outcomes were CAD and diabetes diagnosis measured by logistic regressions and incident disease measured by Cox proportional hazards regression models adjusted for sex, age, body mass index, and smoking status.

The study included 391 481 individuals (median [IQR] age, 58 [51-64] years; 209 235 [53%] female). Genetic variants for HS correlated significantly with variants associated with CAD, diabetes, and plasma levels of high-density lipoprotein cholesterol, triglycerides, and C-reactive protein. Compared with the low-risk group, a high PRS for HS (≥75th percentile) conferred odds ratios of 1.09 (95% CI, 1.06-1.12; P < .001) for CAD and 1.13 (95% CI, 1.10-1.17; P < .001) for diabetes. Estimates remained consistent when examining only incident CAD and diabetes. The PRS for HS was significantly associated with altered expression of 58 plasma proteins. Integrating this proteomic profile and the PRS for HS in a machine learning model improved prediction of CAD and diabetes compared with a reference model based on sex, age, and body mass index.

These findings suggest that a high genetic risk of HS is associated with increased risk of subsequent CAD and diabetes and altered composition of the plasma proteome. Additional investigation into the identified proteins and their potential roles as drug targets is warranted.

This study aims to explore the independent and combined associations of physical activity (PA) in different domains and inflammatory diet with type 2 diabetes mellitus (T2DM).

Data from 8736 American adults from the NHANES 2007-2016 were used. PA in different domains was assessed using the self-reported Global Physical Activity Questionnaire, and dietary inflammatory index was estimated based on 24 h dietary recalls. T2DM diagnosis was determined by a combination of self-report and laboratory data. A multivariate modified Poisson regression model was used to explore the independent and combined associations of moderate-vigorous intensity physical activity (MVPA) and inflammatory diet with T2DM.

PA in the Work MVPA, Recreational MVPA and Total MVPA domains was independently associated with reduced risk of T2DM, and an inflammatory diet was independently associated with elevated risk of T2DM. In the combined analysis, the combination of active and anti-inflammatory within the Work MVPA, Recreational MVPA and Total MVPA fields was associated with the greatest reduced risk of T2DM, and always associated with decreased risk of T2DM in the active group.

Our study emphasizes that the combination of active PA and anti-inflammatory diet is closely associated with the reduced risk of T2DM, and suggests the combination of both for the prevention and treatment of T2DM.

Arduous military training frequently consists of prolonged physical activity, sleep disturbance, and stress that increases musculoskeletal injury risk and performance decrements. Inflammatory and oxidative stress responses have been reported in response to arduous training, but with inconsistencies across markers and with underrepresentation of women. The purpose of the current report was to measure circulating inflammation and oxidative stress responses to military training and to correlate biomarkers with subjective measures of stress and sleep quality as well as military fitness test performance.

Candidates undergoing the 10-wk Marine Corps Officer Candidate School (OCS; 101 men, 62 women) were monitored, with demographic and questionnaire data collected, and blood drawn before and after OCS. Blood was analyzed for six markers of inflammation and three markers of oxidative stress. Associations between biomarkers and questionnaire and fitness test performance were tested.

All measured inflammatory markers as well as plasma antioxidant capacity were elevated following OCS. The inflammatory increase was higher in women for several markers. Sleep disturbance and stress perception were associated with interleukin (IL)-6, IL-10, and C-reactive protein concentrations, suggesting that low sleep disturbance and stress perception were associated with low inflammatory load. In addition, those with the highest inflammation at each time point performed worse on fitness tests than those with low inflammation.

Following arduous military training, the circulating environment in a significant portion of officer candidates resembled chronic low-grade inflammation. This circulating inflammatory environment appeared worse with poor sleep, high stress perception, and poor fitness test performance, with utility observed for C-reactive protein, IL-6, and IL-10 as biomarkers of these responses. Because inflammation may contribute to musculoskeletal injury and performance decrements, minimizing chronic inflammation during military training should be explored.

Chronic systemic inflammation is associated with mortality in patients with chronic kidney disease, cardiovascular disease, and diabetes. The goal of this study was to examine the relationship between pretransplant inflammatory biomarkers (growth differentiation factor-15 [GDF-15], interleukin-6 [IL-6], soluble tumor necrosis factor receptor-1, monokine induced by gamma interferon/chemokine [C-X-C motif] ligand 9 [MIG/CXCL9], monocyte chemoattractant protein-1, soluble FAS, tumor necrosis factor-α, interleukin-15, and interleukin-1β) and death with function (DWF) after kidney transplantation (KT).

We retrospectively measured inflammatory biomarker levels in serum collected up to 1 y before KT (time from blood draw to KT was 130 ± 110 d) in recipients transplanted between January 2006 and December 2018. Kaplan-Meier estimation, Cox regression, and Gradient Boosting Machine modeling were used to examine the relationship between inflammatory biomarkers and DWF.

Our cohort consisted of 1595 KT recipients, of whom 62.9% were male and 83.2% were non-Hispanic White. Over a mean follow-up of 7.4 ± 3.9 y, 21.2% of patients (n = 338) experienced DWF. Patients with the highest quartile levels of GDF-15 (>4766 pg/mL), IL-6 (>6.11 pg/mL), and MIG/CXCL9 (> 5835 pg/mL) had increased rates of DWF, and each predicted mortality independently of the others. When adjusted for clinical factors (age, diabetes, etc), the highest quartile levels of GDF-15 and IL-6 remained independently associated with DWF. Adding inflammatory markers to a clinical Cox model improved the C-statistic for DWF from 0.727 to 0.762 using a Gradient Boosting Machine modeling approach.

These findings suggest that pre-KT serum concentrations of GDF-15, IL-6, and MIG/CXCL9 may help to risk stratify and manage patients undergoing KT and suggests that chronic inflammation may play a role in mortality in KT recipients.

Metribuzin (MBN) is a selective herbicide that adversely damages the vital organs of the body including the liver. Pratensein (PTN) is a novel flavonoid that exhibits marvelous medicinal properties. This experimental trial commenced to elucidate the pharmacotherapeutic strength of PTN to counteract MBN provoked liver toxicity in rats. Thirty-six male albino rats (Rattus norvegicus) were categorized into four groups i.e., the control, MBN (133.33 mg/kg), MBN (133.33 mg/kg) + PTN (20 mg/kg) and PTN (20 mg/kg) alone treated group. Our findings revealed that MBN exposure promoted the expressions of Keap-1 as well as concentrations of ROS and MDA while reducing the gene expressions of Nrf-2 as well as activities of catalase (CAT), glutathione Peroxidase (GPx), glutathione reductase (GSR), heme oxygenase-1 (HO-1), superoxide dismutase (SOD) and glutathione (GSH) contents. The levels of albumin and total proteins were reduced whereas the levels of alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were enhanced following the MBN administration. Moreover, the gene expression of transforming growth Factor-β1 (TGF-β1), matrix metallopeptidase-2 (MMP-2), matrix metallopeptidase-9 (MMP-9), collagen, type I, alpha 1 and type-3 alpha were escalated in response to MBN intoxication. Furthermore, MBN administration cause a sudden upregulation in the levels of NF-κB, IL-1β, TNF-α, IL-6 & COX-2. Besides, MBN exposure enhanced the gene expression of Bax and Caspase-3 while reducing the gene expression of PI3K, Akt and Bcl-2. Additionally, MBN exposure dysregulated the normal histology of liver. However, PTN treatment notably protected the hepatic tissues via regulating abovementioned dysregulations due to its marvelous ROS scavenging potential.

Obesity, a global public health problem, is constantly increasing, so the concerns in preventing and combating it are increasingly focused on the intestinal microbiota. It was found that the microbiota is different in lean people compared to obese individuals, but the exact mechanisms by which energy homeostasis is influenced are still incompletely known. Numerous studies show the involvement of certain bacterial species in promoting obesity and associated diseases such as diabetes, hypertension, cancer, etc. Our aim is to summarize the main findings regarding the influence of several factors such as lifestyle changes, including diet and bariatric surgery, on the diversity of the gut microbiota in obese individuals. The second purpose of this paper is to investigate the potential effect of various microbiota modulation techniques on ameliorating obesity and its comorbidities. A literature search was conducted using the PubMed database, identifying articles published between 2019 and 2024. Most studies identified suggest that obesity is generally associated with alterations of the gut microbiome such as decreased microbial diversity, an increased Firmicutes-to-Bacteroidetes ratio, and increased SCFAs levels. Our findings also indicate that gut microbiota modulation techniques could represent a novel strategy in treating obesity and related metabolic diseases. Although some mechanisms (e.g., inflammation or hormonal regulation) are already considered a powerful connection between gut microbiota and obesity development, further research is needed to enhance the knowledge on this particular topic.

Sex differences exist in type 2 diabetes (T2D), and androgens have been implicated in the etiology of T2D in a sex-specific manner. We therefore aimed to investigate whether androgens play a role in explaining sex differences in glucose homeostasis and incidence of T2D.

We used observational data from the German population-based KORA F4 study (n = 1975, mean age: 54 years, 41% women) and its follow-up examination KORA FF4 (median follow-up 6.5 years, n = 1412). T2D was determined through self-reporting and confirmed by contacting the physicians and/or reviewing the medical charts. Multivariable linear and logistic regression models were employed to explore associations. Mediation analyses were performed to assess direct effects (DE) and indirect effects (IE), and the mediating role of androgens (total testosterone (TT), dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAs)) in the association between sex (women vs. men) and glucose- and insulin-related traits (cross-sectional analysis) and incidence of T2D (longitudinal analysis).

After adjustment for confounders, (model 1: adjusted for age; model 2: model 1 + smoking + alcohol consumption + physical activity), women had lower levels of TT, DHEAs, fasting glucose levels, fasting insulin levels, 2 h-glucose levels and HOMA-IR, compared to men. An inverse association was observed for TT and glucose- and insulin-related traits in men, while a positive association was observed for TT and fasting glucose levels in women. We found a mediatory role of TT on the association of sex with fasting glucose levels (IE: β = 3.08, 95% CI: 2.04, 4.30), fasting insulin levels (IE: β = 0.39, 95% CI:0.30, 0.47), 2 h-glucose levels (IE: β = 12.77, 95% CI: 9.01, 16.03) and HOMA-IR (IE: β = 0.41, 95% CI: 0.33, 0.50). Also, the inconsistent mediatory role of TT was seen on the association of sex with incidence of T2D (DE: 0.12, 95% CI: 0.06, 0.20 and IE: OR = 7.60, 95% CI: 3.43, 24.54). The opposing DE and IE estimates suggest that the association between sex and either glucose homeostasis or the incidence of T2D may differ when TT is considered as a potential mediator, with higher TT levels being beneficial for glucose metabolism or incidence of T2D in men, while in women, detrimental. No mediatory role was observed for either DHEA or DHEAs on glucose homeostasis or the incidence of T2D.

The dimorphic mediatory role of TT highlights its complex role in metabolic health, contributing differently to the glucose dysregulation and risk of T2D in men and women.

The circadian clock plays a vital role in modulating the cellular immune response. However, its role in mediating pro-inflammatory diabetogenic β cell injury remains largely unexplored. Our studies demonstrate that the exposure of β cells to IL-1β-mediated inflammation alters genome-wide DNA binding of core circadian transcription factors BMAL1:CLOCK enriched for genomic sites important for cellular response to inflammation. Correspondingly, conditional deletion of Bmal1 in mouse β cells was shown to impair the ability of β cells to recover from streptozotocin-mediated pro-inflammatory injury in vivo, leading to β cell failure and the development of diabetes. Further data integration analysis revealed that the β cell circadian clock orchestrates the recovery from pro-inflammatory injury by regulating transcriptional responses to oxidative stress, DNA damage, and nuclear factor κB(NF-κB)-driven inflammation. Our study suggests that the β cell circadian clock mediates β cell response and recovery from pro-inflammatory injury common to the pathogenesis of diabetes mellitus.

To investigated the link between the systemic immunity-inflammation index (SII), a new inflammatory biomarker, and the risk of abnormal glucose regulation in non-diabetic population.

Using data from the 2005-2016 National Health and Nutrition Examination Survey (NHANES), we conducted a cross-sectional study on non-diabetic adults with data on SII and glucose regulation markers. We analyzed the relationship between SII and indicators of glucose regulation, including fasting plasma glucose, fasting insulin, hemoglobin A1c, oral glucose tolerance test (OGTT), and states of abnormal glucose regulation like impaired glucose tolerance (IGT), insulin resistance, and prediabetes.

Adjusting for confounders, higher SII levels were significantly associated with a higher OGTT and a greater likelihood of IGT (OR = 2.673, 95% CI: 1.845, 3.873). In subgroup analysis, participants without hyperlipidemia in the highest SII quartile had a 240% higher odds of IGT compared to those in the lowest quartile (OR = 3.407, 95%CI: 1.995, 5.820), an association not observed in those with hyperlipidemia (p for interaction < 0.05).

SII emerges as a useful biomarker for identifying IGT in non-diabetic individuals, specifically in those without hyperlipidemia.

Diabetes is a chronic disease with significant complications, necessitating regular treatment and checkups, which can be costly and time-consuming for patients. To address this, we developed the Sliding Microneedle (MN)-Lateral flow immunoassay strip (LFIAs) device that combines the advantages of MNs and LFIAs to detect IL-6, an independent biomarker for diabetes complications. This device offers rapid and highly sensitive detection of IL-6 by extracting interstitial fluid (ISF) through MNs and transferring it to LFIAs. The stainless MN, embedded in the 3D-printed Sliding MN-LFIAs device, was inserted into the skin at a 20° angle, minimizing blood contamination risk. With a filter paper attached to the MN surface, the device collected 4.65 ± 0.05 μL of ISF containing IL-6 within 90 s. The ISF was then transferred to the LFIAs using a running buffer. After a 15-min reaction, silver enhancement (SE) treatment was applied, allowing for the highly sensitive and specific detection of IL-6 at 102 pg/mL concentrations. The Sliding MN-LFIAs device successfully distinguished between normal and diabetic rat models, demonstrating its potential as an effective tool for detecting diabetes complications quickly and affordably.

An anti-inflammatory diet is characterised by incorporating foods with potential anti-inflammatory properties, including fruits, vegetables, whole grains, nuts, legumes, spices, herbs and plant-based protein. Concurrently, pro-inflammatory red and processed meat, refined carbohydrates and saturated fats are limited. This article explores the effects of an anti-inflammatory diet on non-communicable diseases (NCD), concentrating on the underlying mechanisms that connect systemic chronic inflammation, dietary choices and disease outcomes. Chronic inflammation is a pivotal contributor to the initiation and progression of NCD. This review provides an overview of the intricate pathways through which chronic inflammation influences the pathogenesis of conditions including obesity, type II diabetes mellitus, CVD, autoinflammatory diseases, cancer and cognitive disorders. Through a comprehensive synthesis of existing research, we aim to identify some bioactive compounds present in foods deemed anti-inflammatory, explore their capacity to modulate inflammatory pathways and, consequently, to prevent or manage NCD. The findings demonstrated herein contribute to an understanding of the interplay between nutrition, inflammation and chronic diseases, paving a way for future dietary recommendations and research regarding preventive or therapeutic strategies.

Higher prevalence rates of diabetes and its complications have been reported among individuals with poor physical activity and a sedentary lifestyle. This study explored the influence of six months of moderate-intensity supervised aerobic training on the serum lipid profile, hs-CRP level, and variable-related correlations in prediabetic and type 2 diabetes patients (T2DM).

The study was based on a two-arm parallel group pretest‒posttest comparative design.

A total of 50 subjects who were diagnosed with diabetes for more than five years and aged 30-70 years were included in this study. The subjects were classified into two groups on the basis of their glycated haemoglobin (HbA1c%) values: Group 1 (patients with the prediabetes; HbA1c % ≤ 6.5, n = 25) and Group 2 (patients with the T2DM; HbA1c % ≥ 6.5, n = 25). Blood sugar, HbA1c %, insulin, lipid profile, and highly sensitive CRP (hs-CRP) were measured via colorimetric and immunoassay techniques at baseline and six months postintervention with moderate aerobic exercise.

The results revealed that participation in moderate aerobic training interventions for six months resulted in a significant reduction in BMI, fasting blood sugar, glycosylated haemoglobin, hs-CRP, and lipid profile parameters such as T-Cholest, TG, and LDL-C as well as significant improvement in the level of insulin with a reduction in the values of HOMA-IR towards normal values in the patients with prediabetes (P < 0.01) in group 1 and patients with diabetes in group 2 (P < 0.001). The change in VO2max with good physical fitness significantly improved with the exercise program after six months. The reduced levels of hs-CRP, HOMA-IR, and lipid profile and improved levels of insulin were significantly positively correlated with the levels of glycated haemoglobin (HbA1c%) in the patients with prediabetes (P < 0.01) and those with diabetes (P < 0.001) following six months of moderate aerobic training interventions. Moreover, hs-CRP was positively correlated with T-Cholest, TG, and LDL-C (p = 0.01) and negatively correlated with HDL-C. The data revealed improved glycemic control factors, lipid profiles, and hs-CRP levels as cardio-predictive markers in patients with both prediabetes and diabetes as well. These findings suggest that the anti-inflammatory effect of physical activity gained from moderate exercise training for six months may counteract increased cardiovascular complications associated with increased CRP levels and lipid profiles in prediabetes and T2DM patients.

Moderate aerobic training for six months favourably affects glycemic parameters, lipid profiles, and inflammatory hs-CRP indicators and improves VO2max, an indicator of physical fitness, in prediabetic and diabetic patients. The data obtained suggest the positive effect of moderate exercise training as a protective modulator of cardiovascular disorders, including the dyslipidaemic profile, glycaemic control, and hs-CRP inflammatory markers, in prediabetes and T2DM patients. Thus, regular exercise, owing to its anti-inflammatory effects and ability to improve cardiorespiratory fitness, lipid profiles, blood glucose levels, and insulin resistance, may help reduce the severity of cardiovascular diseases in prediabetes and T2DM patients and healthy controls.

Retrospectively registered with ClinicalTrials.gov PRS under trial identifier ID: NCT06246435 dated 30/01/2024.

This study aimed to analyze the associations of cardiometabolic index (CMI) with diabetic statuses and insulin resistance (IR) using data from the National Health and Nutrition Examination Survey (NHANES) and examined the potential mediating role of inflammation in these correlations.

This study enrolled 9477 participants across four NHANES cycles from 2011 to 2018. The primary outcomes of the study included the risk of having prediabetes, diabetes and the level of the homeostasis model assessment of IR (HOMA-IR). Other outcomes including the levels of fasting blood glucose (FBG), hemoglobin A1c (HbA1c), oral glucose tolerance test (OGTT) results, fasting insulin, the risk of oral hypoglycemic medicine use, insulin use, and retinopathy were also collected and analyzed. Logistic regression model, subgroup analysis, restricted cubic spine (RCS), and Pearson correlation coefficients were conducted to assess the associations of CMI with diabetic statuses and IR. The mediating role of inflammation was evaluated to investigate the potential mechanism of the associations between CMI and diabetic statuses.

Among included participants, the CMI levels in normal participants, prediabetes and diabetes in this study were 0.48, 0.73 and 1.07. After multivariable adjustment, CMI was positively associated with the risk of prediabetes (OR = 1.49, 95% CI = 1.24-1.79), diabetes (OR = 2.14, 95% CI = 1.82-2.50) and the level of HOMA-IR (β = 2.57, 95% CI = 2.14-3.01). Besides, an increased CMI was correlated with higher levels of FBG, HBA1c, OGTT results and fasting insulin as well as the greater risk of oral hypoglycemic medicine use and insulin use. The RCS showed an inverted L-shaped association of CMI with prediabetes and diabetes (P for non-linearity < 0.001). According to Pearson correlation coefficients, higher CMI was linked to higher rises in HOMA-IR (r = 0.224, P < 0.001). Inflammation-related indicators including leukocyte and neutrophil demonstrated significant mediating effects in the associations of CMI with prediabetes (15.5%, 9.8%), diabetes (5.1%, 6.0%) and HOMA-IR (3.3%, 2.6%).

CMI was positively associated with the risk of worse diabetic statuses and higher level of IR while the associations may be partially mediated by inflammation-related indicators, suggesting that CMI could be a promising indicator for the prediction of severe diabetes and IR.

Diabetes mellitus (DM) is predisposing to the development of latent tuberculosis infection (LTBI). An understanding of the underlying factors of LTBI-DM is important for tuberculosis prevention and control. This study aims to evaluate the association between LTBI and DM among the noninstitutionalized civilian population in the United States, focusing on the impact of serum globulins. We performed a cross-sectional study design using public data from 2011 to 2012 National Health and Nutrition Examination Survey, focusing on participants diagnosed with LTBI who were aged 20 and above. Weighted Wilcoxon rank-sum and weighted chi-square tests were used to compare group differences. A multivariable logistic regression model was constructed to assess the association between serum globulin and DM, with subgroup analyses and evaluations of nonlinear relationships. Receiver operating characteristic curves were used to assess the predictive power of the models. A total of 694 participants (512 DM and 182 nonDM) were included in our study and the incidence of DM was 22%. Higher serum globulin levels were significantly associated with an increased risk of DM, with a 21% increase in risk for each unit increase in serum globulin (odds ratio = 1.21, 95% confidence interval [1.03, 1.43], P < .001). The relationship between serum globulin and DM was linear, and higher serum globulin levels were associated with a higher risk of DM, particularly in males (P = .043) and obese individuals (P = .019). The area under the curve for serum globulin predicting DM was 0.795, with an optimal cutoff value of 2.9. Elevated serum globulin levels are significantly associated with an increased risk of DM among individuals with LTBI, highlighting the potential role of serum globulin as a predictive biomarker for DM in this population. However, the specific mechanism between globulin and LTBI-DM needs to be further investigated.

The high prevalence of diabetes mellitus (DM) poses a significant public health challenge, with diabetic kidney disease (DKD) as one of its most serious consequences. It has become increasingly clear that type 2 DM (T2D) and the complications of DKD are not purely metabolic disorders. This review outlines emerging evidence related to the step-by-step contribution of macrophages to the development and progression of DKD in individuals who specifically develop T2D as a result of obesity. The macrophage is a prominent inflammatory cell that contributes to obesity, where adipocyte hypertrophy leads to macrophage recruitment and eventually to the expansion of adipose tissue. The recruited macrophages secrete proinflammatory cytokines, which cause systemic inflammation, glucose dysregulation, and insulin sensitivity, ultimately contributing to the development of T2D. Under such pathological changes, the kidney is susceptible to elevated glucose and thereby activates signaling pathways that ultimately drive monocyte recruitment. In particular, the early recruitment of proinflammatory macrophages in the diabetic kidney produces inflammatory cytokines/chemokines that contribute to inflammation and tissue damage associated with DKD pathology. Macrophage activation and recruitment are crucial inciting factors that also persist as DKD progresses. Thus, targeting macrophage activation and function could be a promising therapeutic approach, potentially offering significant benefits for managing DKD at all stages of progression.

Despite extensive research into extending human healthspan (HS) and compressing morbidity, the mechanisms underlying aging remain elusive. However, a better understanding of the genetic advantages responsible for the exceptional HS of healthy centenarians (HC), who live in good physical and mental health for one hundred or more years, could lead to innovative health-extending strategies. This review explores the role of NLRP3, a critical component of innate immunity that significantly impacts aging. It is activated by pathogen-associated signals and self-derived signals that increase with age, leading to low-grade inflammation implicated in age-related diseases. Furthermore, NLRP3 functions upstream in several molecular aging pathways, regulates cellular senescence, and may underlie the robust health observed in HC. By targeting NLRP3, mice exhibit a phenotype akin to that of HC, the HS of monkeys is extended, and aging symptoms are reversed in humans. Thus, targeting NLRP3 could offer a promising approach to extend HS. Additionally, a paradigm shift is proposed. Given that the HS of the broader population is 30 years shorter than that of HC, it is postulated that they suffer from a form of accelerated aging. The term 'auto-aging' is suggested to describe accelerated aging driven by NLRP3.

The consequence of diabetes on lung cancer overall survival (OS) is debated. This retrospective study used 2 large lung cancer databases to assess comprehensively diabetes effects on lung cancer OS in diverse demographic populations, including health disparity.

The University of Texas MD Anderson Cancer Center database (32 643 lung cancer patients with 11 973 patients with diabetes) was extracted from electronic health records (EHRs) using natural language processing (NLP). Associations were between diabetes and lung cancer prognostic features (age, sex, race, body mass index [BMI], insurance status, smoking, stage, and histopathology). Hemoglobin A1C (HgbA1c) and glucose levels assessed glycemic control. Validation was with a Louisiana cohort (17 768 lung cancer patients with 5402 patients with diabetes) enriched for health disparity cases. Kaplan-Meier analysis, log-rank test, multivariable Cox proportional hazard models, and survival tree analyses were employed.

Lung cancer patients with diabetes exhibited marginally elevated OS or no statistically significant difference versus nondiabetic patients. When examining OS for 2 glycemic levels (HgbA1c > 7.0 or glucose > 154 mg/dL vs HgbA1c > 9.0 or glucose > 215 mg/dL), a statistically significant improvement in OS occurred in lung cancer patients with controlled versus uncontrolled glycemia (P < .0001). This improvement spanned sex, age, smoking status, insurance status, stage, race, BMI, histopathology, and therapy. Survival tree analysis revealed that obese and morbidly obese patients with controlled glycemia had higher lung cancer OS than comparison groups.

These findings indicate a need for optimal glycemic control to improve lung cancer OS in diverse populations with diabetes.