Diabetes Research Articles

Antidiabetic activities of aerial part of Asparagus racemosus Willd. extract: an invitro, invivo, and in silico approach.

Asparagus racemosus Willd., a significant medicinal plant in India's Darjeeling Himalayan region. The current study aims to assess the antidiabetic efficacy of theaerial part of Asparagus racemosus Willd. utilizing a streptozotocin-nicotinamide-induced diabetic rat model. The methanolic extract of plant (ARME) was evaluated for invitro antidiabetic activity through α-glucosidase and α-amylase enzyme suppression assay and assessed invivo in a streptozotocin-induced rat model. A 21-day chronic multiple-dose study of ARME was examined. STZ-induced diabetic rats were treated with metformin (70 mg/kg) and ARME at concentrations of 200 and 400 mg/kg. It was discovered that ARME inhibited the activities of α-amylase and α-glucosidase and showed potent therapeutic effects on the rat's model. ARME helps raise body weight, hemoglobin, and other blood counts and normalizes the serum parameters in the diabetic group. In addition, liver tissues' abnormal levels of the antioxidant enzymes glutathione and lipid peroxides were returned to those of control animals. HPTLC study revealed the presence of stigmasterol, which showed a strong affinity for the proteins linked to diabetes mellitus through insilico study. As a result of these findings, ARME inhibits the activity of digestive enzymes and has antioxidant and antihyperglycemic effects in STZ-nicotinamide-induced diabetic rats.

Comparison of hypothermic and normothermic cardiopulmonary bypass in patients undergoing coronary artery bypass graft surgery

Objectives: Coronary artery bypass graft (CABG) surgery operations accompanied by cardiopulmonary bypass (CPB) are the most prominent treatment options. One of the basic application principles of the CPB system is the protection of vital organs by reducing metabolic rate and oxygen consumption with hypothermia. In this study, we aimed to investigate the effects of normothermia and hypothermia applications on clinical outcomes in CABG operations performed with CPB. Methods: This single-center study was planned retrospectively. Patients who underwent isolated CABG operation with CPB at Şanlıurfa Mehmet Akif İnan Training and Research Hospital between January 01, 2020, and January 01, 2022, were included. A total of 120 patients, 60 of whom underwent hypothermic and 60 normothermic cardiac bypass, were included in the study after applying the exclusion criteria. Results: There was no difference between the groups in terms of age, gender, diabetes mellitus, hypertension, left ventricular ejection fraction, and body surface area characteristics (P>0.05). In the normothermia group, urea, creatinine, direct bilirubin, and lactate levels were significantly higher in the first postoperative day blood values (P=0.003, P=0.04, P=0.028, P=0.005, and P<0.001, respectively). Positive inotropic agent requirement and defibrillation requirement after cross-clamping were significantly higher in the hypothermia group (P=0.006 and P=0.045, respectively). Conclusions: In CABB operations performed with CPB, normothermia and hypothermia applications may have beneficial effects on different clinical situations.

Impact of obesity, genetic predisposition and comorbidities on pregnancy-related hypertension

Purpose: This study aims to explore the impact of obesity, genetic predisposition, and comorbidities on pregnancy-related hypertension. Given the rising prevalence of maternal obesity and associated metabolic disorders, understanding how these factors contribute to hypertensive complications during pregnancy is crucial for developing effective prevention and management strategies. The study also examines the role of genetic susceptibility and pre-existing medical conditions in exacerbating hypertensive risks, emphasizing the need for a holistic approach in maternal healthcare. Research Design and Methodology: This study employs a systematic literature review (SLR) to synthesize findings from existing research on the relationship between obesity, genetic factors, and comorbidities with pregnancy-related hypertension. Relevant peer-reviewed articles from Elsevier, Emerald, Wiley, and Springer published after 2018 were analyzed to identify key trends, mechanisms, and clinical implications. The review integrates evidence from obstetrics, endocrinology, genetics, and public health to understand the topic comprehensively. Findings and Discussion: The study reveals that obesity significantly contributes to hypertensive disorders in pregnancy through mechanisms such as endothelial dysfunction, chronic inflammation, insulin resistance, and RAAS activation. Genetic predisposition, particularly polymorphisms in RAAS-related genes (AGT, ACE, AGTR1) and endothelial function genes (eNOS, VEGF), is strongly associated with increased hypertension risk. Additionally, pre-existing conditions such as diabetes mellitus, chronic hypertension, kidney disease, and autoimmune disorders further aggravate hypertensive complications. Implications: The findings emphasize the necessity for early screening programs, personalized treatment approaches, and interdisciplinary prenatal care. Healthcare policymakers should develop standardized guidelines for managing hypertensive pregnancies complicated by obesity and comorbidities. The study highlights the importance of lifestyle interventions, genetic screening, and pharmacological advancements in reducing pregnancy-related hypertension risks and improving maternal-fetal health outcomes.

Metformin versus insulin in glycemic control in pregnancy (MevIP): a randomized clinical trial protocol

BackgroundGestational diabetes is one of the most prevalent diseases in pregnancy, with an incidence of 5 to 18% in Brazil, and is associated with high morbidity rates. The first-line treatment is insulin, although some recent studies have indicated that metformin might also be effective. Metformin is safe in pregnancy and appears to produce better results than insulin, including reduced gestational weight gain (GWG) and smaller gestational-age newborns. Few studies have been conducted on this topic in low- and middle-income countries.MethodsWe designed an open randomized controlled trial comparing two treatments for pregnant women with type II diabetes mellitus (DM) and gestational diabetes (DMG): the metformin group (intervention) and the insulin group (as a routine service). The primary outcome is glycemic control. The secondary outcomes are GWG, the occurrence of hypertensive syndromes, macrosomia, and neonatal hypoglycemia. The sample will comprise 92 pregnant women, 46 per group. The inclusion criteria will be GDM or type II DM requiring medication for glycemic control, singleton pregnancy, and gestational age under 34 weeks. The exclusion criteria will be current treatment with any medication for glycemic control, type I DM, and intolerance to the study medications (metformin or insulin). Women will be routinely followed during antenatal care, childbirth, and the postpartum period. Statistical analyses will include the intention-to-treat approach and a comparison between the two groups.DiscussionConsidering the Brazilian socioeconomic reality and the safety of metformin demonstrated in previous trials, we expect that the MevIP study will demonstrate that metformin is an adequate and appropriate medication for GDM treatment in the Brazilian population, representing an alternative to insulin for GDM.Trial registrationThis protocol has been registered prospectively in ReBEC under the ID RBR-3j3cktx in August 11, 2023.

PRKD2 as a novel target for targeting the diabetes–osteoporosis nexus

Diabetes mellitus (DM) and osteoporosis (OP) co-morbidity (DMOP) pose major health challenges owing to their complex pathophysiological interactions. The aim of this study was to identify and validate key genes implicated in the pathogenesis of both conditions. By employing the Mfuzz time-series gene clustering method combined with transcriptome sequencing of patient serum, we systematically delineated gene expression patterns during the transition from a healthy state through DM to DMOP. These findings were further validated using external datasets, and a series of functional enrichment analyses, gene set enrichment analyses, and immune cell infiltration studies were conducted. Our analyses revealed a distinct progression pattern from a normal state through DM to DMOP, characterized by dynamic gene expression changes. Notably, PRKD2 emerged as a significantly downregulated gene in DMOP, highlighting its crucial role in disease pathogenesis. Further analyses revealed the involvement of PRKD2 in key signaling pathways, especially the Wnt and IL-18 pathways, which are critical for bone and glucose metabolism. Validation in cellular and animal models confirmed the role of PRKD2 in apoptosis and bone metabolism, emphasizing its therapeutic potential. In conclusion, our findings establish PRKD2 as a pivotal molecule in DMOP, offering fresh insights into its mechanisms and affirming its value as a therapeutic target.

Unsupervised machine learning clustering approach for hospitalized COVID-19 pneumonia patients

BackgroundIdentification of distinct clinical phenotypes of diseases can guide personalized treatment. This study aimed to classify hospitalized COVID-19 pneumonia subgroups using an unsupervised machine learning approach.MethodsWe included hospitalized COVID-19 pneumonia patients from July to September 2021. K-means clustering, an unsupervised machine learning method, was performed to identify clinical phenotypes based on clinical and laboratory variables collected within 24 hours of admission. Variables were normalized before clustering to ensure equal contribution to the analysis. The optimal number of clusters was determined using the elbow method and Silhouette scores. Cox proportional hazard models were used to compare the risk of intubation and 90-day mortality across the identified clusters.ResultsThree clinically distinct clusters were identified among 538 hospitalized COVID-19 pneumonia patients. Cluster 1 (N = 27) consisted predominantly of males and showed significantly elevated serum liver enzymes and LDH levels. Cluster 2 (N = 370) was characterized by lower chest x-ray scores and higher serum albumin levels. Cluster 3 (N = 141) was characterized by older age, diabetes mellitus, higher chest x-ray scores, more severe vital signs, higher creatinine levels, lower hemoglobin levels, lower lymphocyte counts, higher C-reactive protein, higher D-dimer, and higher LDH levels. When compared to cluster 2, cluster 3 was significantly associated with increased risk of 90-day mortality (HR, 6.24; 95% CI, 2.42–16.09) and intubation (HR, 5.26; 95% CI 2.37–11.72). In contrast, cluster 1 had a 100% survival rate with a non-significant increase in intubation risk compared to cluster 2 (HR, 1.40, 95% CI, 0.18–11.04).ConclusionsWe identified three distinct clinical phenotypes of COVID-19 pneumonia patients, with cluster 3 associated with an increased risk of respiratory failure and mortality. These findings may guide tailored clinical management strategies.

Triglyceride-glucose index is associated with microcirculatory resistance in patients with type 2 diabetes and STEMI undergoing primary PCI

The triglyceride-glucose (TyG) index is emerging as a promising marker for insulin resistance and serves as an independent risk predictor for cardiovascular outcomes. The coronary angiography-derived index of microcirculatory resistance (AMR) is computed to evaluate coronary microcirculation. However, the association between the TyG index and the AMR in patients with type 2 diabetes mellitus (T2DM) and ST-segment elevation myocardial infarction (STEMI) remains unclear. We consecutively recruited 168 patients with T2DM and STEMI who underwent primary percutaneous coronary intervention (pPCI) at Taizhou People’s Hospital from January 2022 to December 2023. Patients were classified into low AMR group (AMR < 2.5) and high AMR group (AMR ≥ 2.5). The TyG index was calculated using the formula: ln [plasma triglyceride (mg/dL) × fasting blood glucose (mg/dL)/2]. The study enrolled 81 patients in the low AMR group and 87 in the high AMR group, with the TyG index being significantly higher in the high AMR group. Multivariable logistic regression analysis revealed a significant association between the TyG index and high AMR after adjusting for confounding variables (odds ratio: 2.449, 95% confidence interval: 1.421–4.220, and p = 0.001). The area under the curve for the TyG index predicting high AMR was 0.650 (95% confidence interval: 0.57–0.73, p < 0.001), with a cut-off value of 9.57. Our findings indicate that the TyG index is significantly associated with AMR in T2DM patients with STEMI undergoing pPCI, suggesting it may serve as a valuable predictor of high AMR in this population.

Cutaneous wound healing in type 2 diabetes db/db mice was impaired with specific changes in proinflammatory cytokine expression

In db/db mice, cutaneous wound healing was delayed, and excessive wound exudates enlarged the wound. However, the relationship between enlarged wounds and proinflammatory cytokine expression remains unknown. Therefore, we investigated the expression of proinflammatory cytokines Tnf-α and Il-6 in cutaneous wound healing with diabetes. In this study, 12 C57BL/6J mice (wild-type: WT) and 14 db/db mice were subjected to full-thickness wound injuries. Wound healing was assessed until day 14, and wound tissues were harvested on days 7, 9, 11, and 14. The wound areas increased for 4 days, gradually increased until day 9, and stabilized until day 14 in the db/db group, but increased for 3 days, rapidly decreased until day 12, and gradually decreased until day 14 in the WT group. On day 14, the wound area in the db/db group was significantly larger than that in the WT group (p < 0.01). The relative expressions of the Tnf-α and Il-6 in the db/db group were significantly higher than those in the WT group on days 7–14, and on days 11 and 14, respectively (p < 0.05). Our study showed that cutaneous wound healing was delayed with wound expansion and the expression of Tnf-α and Il-6 was high throughout the measurement time points in db/db mice. These abnormal expressions could influence impaired cutaneous wound healing in diabetic mellitus.

Effects of melatonin supplementation on oxidative stress, and inflammatory biomarkers in diabetic patients with chronic kidney disease: a double-blind, randomized controlled trial

Background and objectivesChronic kidney disease (CKD) is a progressive illness linked to higher rates of morbidity and death. One of the main causes of CKD is diabetes mellitus (DM), and oxidative stress is essential to the disease's development. It has been demonstrated that the natural antioxidant melatonin reduces inflammation and oxidative damage in renal tissues. Given the lack of robust evidence, this double-blind clinical trial sought to investigate the effects of melatonin supplementation on oxidative stress and inflammatory markers in diabetic CKD patients.Materials and methodsThis trial included 41 diabetic patients with CKD (stages 3–4) from Shariati Hospital, Tehran, Iran. For ten weeks, participants were randomized to receive either a placebo or 5 mg of melatonin twice a day. Baseline characteristics, dietary intake, physical activity, and anthropometric measurements were recorded. Oxidative stress (TAC, TOS, MDA) and inflammatory markers (IL-6, hs-CRP) were measured before and after the intervention. Statistical analysis was performed using SPSS, with significance set at p < 0.05.ResultsThe 10-week trial was completed by 41 participants in total, and no adverse effects were noted. Dietary intake, physical activity, and anthropometric parameters did not significantly differ between the melatonin and control groups in baseline characteristics. Melatonin supplementation decreased oxidative stress and inflammatory biomarkers, including hs-CRP, MDA, TOS, and IL-6. However, these changes were not statistically significant.ConclusionOur study showed that melatonin supplementation did not significantly affect oxidative stress or inflammatory markers, including TAC, TOS, MDA, IL-6, and hs-CRP, in diabetic patients with CKD. Despite a decrement in TOS, MDA, IL-6, and hs-CRP levels after 10 weeks, this was not statistically significant. Further studies with larger sample sizes, greater dosages, and longer follow-up periods are recommended.

Investigation of the safety of Radium-223 chloride in combination with external beam radiotherapy for bone metastases of prostate cancer.

This study aimed to investigate the safety of combining radium-223 chloride (Ra-223) therapy with external beam radiation therapy (EBRT) for patients with multiple bone metastases from castration-resistant prostate cancer (CRPC), including lesions requiring urgent treatment such as those causing neurological symptoms due to spinal cord compression. We retrospectively analyzed data from patients with CRPC and bone metastases treated with Ra-223 therapy at our hospital between September 1, 2018, and December 31, 2023. Adverse events were evaluated using the Common Terminology Criteria for Adverse Events version 4.0. Of the 23 patients referred, data from 17 were included; 8 received concurrent Ra-223 therapy and EBRT, whereas others received only Ra-223 therapy. The median follow-up period was 20months. Grade (G) 2 or higher adverse events occurred in seven patients (41.2%), and G 3 or higher in 2 (11.7%). None of the patients who received EBRT with fields involving the gastrointestinal tract experienced diarrhea, constipation, bleeding, perforation, or obstruction. Ra-223 therapy with EBRT did not increase adverse events compared with studies of Ra-223 therapy without EBRT. One case of G 5 Pneumocystis carinii pneumonia, likely because of steroid use for neurological symptoms and the patient's underlying diabetes mellitus, was noted. The effects of EBRT cannot be entirely excluded, so minimizing field size and dose is recommended when combining Ra-223 therapy and EBRT. Our findings indicate that concurrent Ra-223 therapy and EBRT could be safe for managing patients with symptomatic bone metastases and castration-resistant prostate cancer who require specialized treatment, provided sufficient attention is given to the field and the prescribed dose.

Models based on dietary nutrients predicting all-cause and cardiovascular mortality in people with diabetes

Dietary intervention plays a vital role in improving the prognosis of people with diabetes mellitus (DM). Currently, there is a lack of systematic analysis of the relation between dietary nutrients and long-term mortality risk in people with DM. The study aims to establish models predicting long-term mortality and explore dietary nutrients associated with reduced long-term events to guide daily dietary decisions in people with DM. The retrospective cohort study collected 5060 participants with DM from the National Health and Nutrition Examination Survey (NHANES) 1999–2018. The least absolute shrinkage and selection operator (LASSO) regression and random forest (RF) algorithm were applied to identify key mortality-related dietary factors, which were subsequently incorporated into risk prediction nomogram models. The receiver operating characteristic (ROC) curve, calibration plot and decision curve analysis (DCA) were utilized to evaluate the performance of the models. The association of key dietary nutrients with all-cause and cardiovascular mortality were visualized by restricted cubic spline (RCS) models both in the whole and subgroups by sex, age, drinking and smoking status. The overall median age of the cohort was 62.0 years (interquartile range (IQR) 52.0–70.0), 2564 (50.67%) being male. During a median follow-up period of 56.0 months, 997 (19.70%) all-cause deaths were recorded, with 219 (21.97%) of which being ascribed to cardiovascular disease. The nomogram models based on key dietary nutrients identified by LASSO and RF demonstrated a significant predicative value for all-cause and cardiovascular mortality. Dietary fiber and magnesium were the common predictive nutrients in the two nomogram models. The RCS curve revealed that dietary fiber and magnesium were negatively associated with long-term mortality in the whole and subgroups of people with DM after adjustment of potential confounders. The diet of people with DM is closely associated with mortality. The nomogram models based on dietary nutrients can predict long-term mortality of people with DM, and the higher intake of dietary fiber and magnesium was associated with reduced risks of both long-term all-cause and cardiovascular mortality.

Association of peripheral neuropathy with dry eye disease and meibomian gland dysfunction in patients with type 1 diabetes.

To explore the relationship between dry eye disease and type 1 diabetes mellitus (DM) and also to identify whether diabetic peripheral neuropathy (DPN) was a significant predictor for the development of dry eye disease. This prospective cross sectional study involved patients with type 1 DM and aged- and sex-matched healthy controls. All of the participants underwent dry eye tests including meibomian gland function. Based on neurologic examination and electromyography findings, diabetic patients were grouped as DPN + and DPN-. All findings were compared and predictive factors for dry eye disease were identified. Of the 97 patients with type 1 DM, 42 (43.3%) were diagnosed as DPN. In patients with DM, there was a significant increase in the ocular surface disease index, corneal surface staining, eyelid margin abnormality and meibomian gland dysfunction and a significant decrease in tear break-up time and Schirmer's I test (p < 0.05). Measurements of dry eye tests were more severe with the presence of DPN (p < 0.05). Age of the patients, duration of DM and HbA1c level were significantly correlated with ocular surface and meibomian gland dysfunction parameters (p < 0.05). Age of the patients (p < 0.001), duration of DM (p = 0.001), HbA1c level (p = 0.036) and presence of DPN (p < 0.001) were found to be the independent and significant predictors of dry eye disease. Type 1 DM was found to be significantly associated with ocular surface abnormalities including meibomian gland dysfunction. Furthermore, age of the patients, duration of DM, HbA1c level and presence of DPN were predictive factors of dry eye disease in type 1 DM.

Prevalence and determinants of diabetes mellitus in 2,338 long-term Dutch childhood cancer survivors (DCCS-LATER2 Study).

Diabetes mellitus (DM), a possible adverse effect of childhood cancer treatment, is strongly associated with cardiovascular disease and early mortality in adult childhood cancer survivors (CCS). Here, we assess the prevalence and determinants of DM in our nationwide CCS cohort. In this cross-sectional study, the prevalence of DM was assessed in 2,338 CCS, using the Lifelines cohort (n=132,226 adults with no history of cancer) as a reference. DM was defined through serum glucose measurement (fasting glucose ≥7.0mmol/L or non-fasting ≥11.1mmol/L) and/or self-report (previous diagnosis and/or medication use). Multivariable logistic regression models, adjusted for age, sex, and BMI, were used to assess the cohort effect on the presence of DM. Multivariable logistic regression analysis was used to identify determinants of DM in CCS. Survivors (median age 34.7 years, median follow-up time 27.1 years) showed increased odds for hyperglycemia (aOR=2.72, 95%CI=2.06-3.59), previous DM diagnosis (aOR=3.03, 95%CI=2.33-3.95), and anti-diabetic medication use (aOR=2.94, 95%CI=2.17-3.99), compared to the reference cohort. Age (OR=4.32, 95%CI=1.84-10.15, >35 versus 18-35 years), BMI (OR=1.12, 95%CI=1.08-1.16, per point), family history of DM (OR=2.38, 95%CI=1.51-3.76), prior abdominal/pelvic radiotherapy (OR=4.19, 95%CI=2.32-7.55), total body irradiation (OR=14.31, 95%CI=6.98-29.34), hypogonadism (OR=2.40, 95%CI=1.15-4.99), hypertension (OR=1.71, 95%CI=1.06-2.76), and dyslipidemia (OR=3.81, 95%CI=2.15-6.75) were associated with DM in CCS. A significant interaction between age and sex on the development of DM in survivors was identified. The identified three-fold increased risk of DM in CCS, along with the clinically relevant -and some modifiable- determinants, underscores the importance of early risk-based screening and the exploration of lifestyle interventions in this population.

Chlorhexidine gluconate application, diabetes, revision surgery, and extended operative time increase risk for penile implant infection.

Chlorhexidine gluconate (CHG) (0.05%) has recently been suggested as a dip and irrigation solution at time of inflatable penile prosthesis (IPP) surgery. This study evaluated infection rates before and after implementing CHG protocol while investigating concurrent risk factors contributing to post operative infections. A retrospective, consecutive cohort study was performed that included patients who underwent insertion of a Coloplast Titan IPP including both virgin and revision cases between 2021 and 2024. Cases performed from January 2021 to August 2022 utilized rifampin/gentamicin for dip and vancomycin/gentamicin for irrigation (ABX), whereas those from October 2022 to May 2024 utilized CHG for both dip and irrigation. Perioperative risk factors including dip and irrigation solution used at time of surgery were compared between groups. We defined the incidence of postoperative infection and risk factors associated with infection in each group. The incidence of infection was significantly higher in the 0.05% CHG group (13/377) compared to the ABX group (0/320) (P< .001). When analyzed separately by subgroup, virgin cases treated with CHG for dip and irrigation demonstrated a significantly higher infection rate (7/315) compared to those in the ABX group (0/280) (P= .012). Similarly, in revision cases, the CHG group also exhibited a significantly higher infection rate (0/40) than the ABX group (6/62) (P= .043).Univariable analysis of the CHG cohort identified three significant risk factors for infection: diabetes mellitus (DM), extended operative time (OP), and revision surgery (P= .003, .001, and < .001, respectively). Multivariable regression analysis revealed that patients with DM had a 5.7-fold increased risk of infection (OR: 5.70, P= .004), while those undergoing revision surgery faced a 5.3-fold higher risk (OR: 5.26, P= .004). Additionally, each minute increase in OP was associated with a 1% higher infection risk (OR: 1.01 per minute, P= .007). These associations remained significant after adjusting for all variables in the model. Prosthetic surgeons should be cautious about adopting 0.05% CHG for both dip and irrigation in the absence of strong clinical evidence demonstrating its non-inferiority to antibiotic solutions. This is the first clinical study reporting infection rates after IPP surgery using 0.05% CHG for both dip and irrigation. While retrospective and non-randomized, we present a relatively large sample size of patients. Our findings identify four risk factors for penile prosthesis infection: usage of the 0.05% CHG solution for dip and irrigation solution of Coloplast hydrophilic-coated devices, DM, revision surgery, and extended OP.

A sex-disaggregated analysis of the prognostic value of lean type 2 diabetes mellitus in the adult population with acute myocardial infarction

BackgroundEmerging evidence has demonstrated the unfavourable cardiovascular risk of individuals with lean type 2 diabetes mellitus (T2DM). Our study aims to investigate the prognostic value of lean T2DM in patients with acute myocardial infarction (AMI), stratified by sex.MethodsThe study cohort examines the clinical characteristics and long-term outcomes of individuals with AMI, stratified by four phenotypes based on T2DM and lean body category—lean T2DM, non-lean T2DM, lean non-T2DM and non-lean non-T2DM. The primary outcome was long-term all-cause mortality. Cox regression model was constructed to investigate the associations of lean and non-lean T2DM phenotypes with mortality, adjusted for age, ethnicity, previous AMI, AMI type, chronic kidney disease, angiotensin converting enzyme inhibitor or angiotensin receptor blockers, beta-blockers, and smoking status.ResultsA cohort of 9545 AMI patients was examined, with a mean follow-up duration of 3.4 ± 2.4 years. Majority had the non-lean T2DM phenotype (40.4%), followed by non-lean non-T2DM (29.8%), lean non-T2DM (15.9%), and lean T2DM (13.9%). In the T2DM group, one-quarter was lean (N = 1324), while the vast majority (74.5%) was non-lean. Individuals with lean T2DM tended to be female and older. Patients with lean T2DM had the highest rates of heart failure (23.3%, p < 0.001), cardiogenic shock (9.1%, p = 0.036), and long-term all-cause mortality (32.6%, p < 0.001). Cox regression demonstrated that lean T2DM was an independent predictor of mortality (adjusted hazard ratio [aHR] 1.171, 95% CI 1.040–1.319, p = 0.009) after adjustment. The presence of higher mortality risk following AMI was present in males (aHR 1.201, 95% CI 1.037–1.391, p = 0.015), but not in females (aHR 1.066, 95% CI 0.869–1.308, p = 0.538).ConclusionsThe lean T2DM phenotype was present in one-quarter of the AMI cohort with T2DM. The lean T2DM phenotype was an independent predictor of long-term mortality following AMI, although this association was stronger in males than in females.

The protective role of SGLT2 inhibitors on aortic aneurysm mediated by oxidative stress and inflammation in type 2 diabetes mellitus

BackgroundSodium-glucose transport protein 2 inhibitors (SGLT2i) have been widely used to treat patients with type 2 diabetes mellitus (T2DM) and have demonstrated protective effects against certain cardiovascular diseases. However, no clinical research has been conducted to explore the relationship between SGLT2i and the risk of aortic aneurysm (AA).MethodsWe extracted and analyzed the data of 4964 patients with T2DM from the First Affiliated Hospital of Zhengzhou University during July 2017 to January 2023. Multivariate Cox models, interaction analysis and Kaplan–Meier curves were performed to approximate the associations of SGLT2i therapy on the risk of AA. A sensitivity analysis was performed to test the robustness of results. Mediation analyses explored the roles of inflammatory (neutrophils, lymphocytes, C-reactive protein and alkaline phosphatase) and oxidative stress (gamma glutamyl transferase, total bilirubin, and uric acid) markers in the associations between SGLT2i and AA.ResultsA total of 1942 SGLT2 inhibitor (SGLT2i) users (39.12%) and 3022 non-SGLT2 inhibitor (NonSGLT2i) users were included in final analysis. After full adjustment for potential risk factors, SGLT2i patients were associated with a lower risk of aortic aneurysm (HR, 95% CI 0.91, 0.89–0.98, p = 0.001). Dapagliflozin showed the greatest difference for reduction of aortic aneurysm incidence (HR, 95% CI 0.84, 0.80–0.95, p = 0.011). Subgroup analysis indicated that use of SGLT2i lower the risk of aortic aneurysm in some subgroups of T2DM patients. The sensitivity analysis demonstrated the robustness of the results. CRP, lymphocytes, neutrophils, and uric acid were significantly associated with both SGLT2i and AA, with mediation proportions of 13.35%, 8.83%, 9.67% and 31.17%, respectively.ConclusionsOur study suggested that patients using SGLT2i may have a lower risk of aortic aneurysm, and this effect could potentially be mediated by inflammation and oxidative stress. Further mechanistic and prospective studies are required to verify this association.Graphical abstract

Identification and study of mood-related biomarkers and potential molecular mechanisms in type 2 diabetes mellitus.

A significant correlation between type 2 diabetes mellitus (T2DM) and mood has been reported. However, the specific mechanism of mood's role in T2DM is unclear. This study aims to discover mood-related biomarkers in T2DM and further elucidate their underlying molecular mechanisms. The GSE81965 and GSE55650 datasets were sourced from public databases, and mood-related genes (MRGs) were retrieved from previous literature. Initially, differentially expressed MRGs (DE-MRGs) were obtained by combining differential expression analysis and weighted gene co-expression network analysis (WGCNA). Subsequently, the DE-MRGs were incorporated into the LASSO and SVM to identify diagnostic biomarkers for T2DM. Four machine learning methods were utilized to construct the diagnostic models in T2DM, and the model with the optimal algorithm was screened. Further, based on biomarkers, functional enrichment, immune infiltration, and regulatory network analyses were conducted to excavate deeper into the pathogenesis of T2DM. In vivo experiments were used to validate the expression of the biomarkers. A total of 23 DE-MRGs were identified by overlapping 723 DEGs and 64 key modules, and there were strong positive correlations between these DE-MRGs. Afterward, KCTD16, SLC8A1, RAB11FIP1, and RASGEF1B were identified as biomarkers associated with mood in T2DM, and they had favorable diagnostic performance. Meanwhile, the RF diagnostic model constructed based on biomarkers was performed optimally and had high diagnostic accuracy for T2DM patients. Animal experiments indicated that expression levels of SLC8A1, RAB11FIP1, and RASGEF1B in T2DM were consistent with the microarray results.In conclusion, KCTD16, SLC8A1, RAB11FIP1, and RASGEF1B were identified as biomarkers related to mood in T2DM.

The Issues of Stress and its Reduction Methods in Modern Science

In everyday life, the word "stress" is often used as a synonym for strong excitement, emotions. But this concept is much broader. Stress is the body's reaction to any irritating effects: problems at work, exams, hunger, lack of sleep, even fluctuations in atmospheric pressure. For many people, such stresses interfere with normal psychological, physical and social functioning. Prolonged stress damages the mechanisms of self-regulation of the body and leads to subsequent disturbances of biorhythms. The natural cycle of sleep and wakefulness changes, as a result, performance and self-control decrease, memory and attention deteriorate. Daily fluctuations in hormone levels, breathing rhythms and heartbeat are also disrupted. Chronic stress weakens the immune system, suppresses the protective reactions and barrier functions of the cells of the gastrointestinal tract and skin, which complicates the course and prognosis of any somatic diseases, including infectious. As a result, stress increases the risk of so-called "diseases of civilization" and contributes to their development: hypertension, diabetes mellitus, bronchial asthma, chronic pain, immune disorders and many others

Development and validation of a novel bleeding risk prediction tool for aspirin users with a low body mass index

Aspirin is commonly utilized in the management and prevention of various diseases. However, in specific individuals, particularly those with low body mass index (BMI), aspirin can elevate the risk of bleeding. Achieving a delicate equilibrium between the desirable antiplatelet effects and potential bleeding complications is a notable consideration. The objective of this study was to create a novel bleeding risk prediction tool for aspirin users with a low BMI. A total of 2436 aspirin users with a low BMI were included in this study conducted at the Affiliated Dongyang Hospital of Wenzhou Medical University. Patient data, comprising demographics, clinical characteristics, comorbidities, medical history, and laboratory tests, were collected. The patients were randomly divided into two groups, with a 7:3 ratio, for model development and internal validation purposes. The identification of clinically significant features associated with bleeding was achieved through the utilization of the Least Absolute Shrinkage and Selection Operator (LASSO) regression and boruta analysis. Subsequently, these important features underwent multivariate logistic regression analysis. Based on independent bleeding risk factors, a logistic regression model was constructed and presented as a nomogram. Model performance was evaluated using metrics such as the area under the curve (AUC), calibration curves, decision curve analysis (DCA), clinical impact curve (CIC), and net reduction curve (NRC) in both the training and testing sets. LASSO analysis identified two clinical features, while Boruta analysis identified nine clinical features out of a total of 21 features. Subsequent multivariate logistic regression analysis selected significant independent risk factors. The boruta model, which demonstrated the highest AUC, consisted of six clinical variables: hemoglobin, platelet count, previous bleeding, tumor, smoke, and diabetes mellitus. These variables were integrated into a visually represented nomogram. The model exhibited an AUC of 0.832 (95% CI: 0.788–0.875) in the training dataset and 0.775 (95% CI: 0.698–0.853) in the test dataset, indicating excellent discriminatory performance. Calibration curve analysis revealed close alignment with the ideal curve. Furthermore, DCA, CIC, and NRC demonstrated favorable clinical net benefit for the model. This study has successfully created a novel risk prediction tool specifically designed for aspirin users with a low BMI. This tool enables the stratification of low BMI patients based on their anticipated bleeding risk.

MRSA-positive sternoclavicular septic arthritis mimicking mediastinal malignancy in a patient with multiple injection history: a rare case report

Introduction and importance: Infection of the sternoclavicular joint is exceptionally rare, accounting for less than 1% of bone infections. The presence of MRSA-positive septic arthritis in the sternoclavicular joint, coupled with its resemblance to mediastinal conditions and a history of multiple injections, presents a rare and complex clinical case that demands thorough evaluation and management. Case presentation: A 60-year-old male with a complex medical history, including hypertension, diabetes mellitus, hepatitis C, and recurrent cellulitis due to multiple IV and IM injections, presented with drowsiness and a painful, erythematous swelling of the left anterior chest wall. Clinical examination revealed pallor, distended abdomen, and decreased left-sided airway entry. Diagnostic workup showed elevated creatinine, metabolic acidosis, and inflammatory markers. Imaging revealed extensive soft tissue swelling and a mediastinal mass. A core biopsy confirmed severe acute and chronic inflammation, abscess formation, and granulation tissue suggestive of an infectious etiology. CT scans further identified sternoclavicular septic arthritis, a rare diagnosis. Clinical discussion: This case report describes MRSA-positive sternoclavicular septic arthritis in a patient with a history of tramadol and multivitamin injections. Sternoclavicular joint (SCJ) infection is rare, complicating differentiation from mediastinal malignancies. Successful management required embolization, IV antibiotics, and physiotherapy. Conclusion: MRSA-positive sternoclavicular septic arthritis, mimicking mediastinal malignancy, presents diagnostic challenges. Successful management involves tailored strategies, interdisciplinary collaboration, and consideration of IV drug injections.