CD47 decline in pancreatic islet cells promotes macrophage-mediated phagocytosis in type Ⅰ diabetes

BACKGROUND Type Ⅰ diabetes(T1D)is characterized by insulin loss caused by inflammatory cells that excessively infiltrate and destroy the pancreas,resulting in dysregulation of tissue homeostasis,mechanobiological properties,and the immune response.The streptozotocin(STZ)-induced mouse model exhibits multiple features of human T1D and enables mechanistic analysis of disease progression.However,the relationship between the mechanochemical signaling regulation of STZ-induced T1D and macrophage migration and phagocytosis is unclear.AIM To study the mechanochemical regulation of STZ-induced macrophage response on pancreatic beta islet cells to gain a clearer understanding of T1D.METHODS We performed experiments using different methods.We stimulated isolated pancreatic beta islet cells with STZ and then tested the macrophage migration and phagocytosis.RESULTS In this study,we discovered that the integrin-associated surface factor CD47 played a critical role in immune defense in the STZ-induced T1D model by preventing pancreatic beta islet inflammation.In comparison with healthy mice,STZ-treated mice showed decreased levels of CD47 on islet cells and reduced interaction of CD47 with signal regulatory proteinα(SIRPα),which negatively regulates macrophage-mediated phagocytosis.This resulted in weakened islet cell immune defense and promoted macrophage migration and phagocytosis of target inflammatory cells.Moreover,lipopolysaccharide-activated human acute monocytic leukemia THP-1 cells also exhibited enhanced phagocytosis in the STZ-treated islets,and the aggressive attack of the inflammatory islets correlated with impaired CD47-SIRPαinteractions.In addition,CD47 overexpression rescued the pre-labeled targeted cells.CONCLUSION This study indicates that CD47 deficiency promotes the migration and phagocytosis of macrophages and provides mechanistic insights into T1D by associating the interactions between membrane structures and inflammatory disease progression.

Perception of difficulty and glucose control:Effects on academic performance in youth with type Ⅰ diabetes

AIM:To investigate whether perceptions of task difficulty on neuropsychological tests predicted academic achievement after controlling for glucose levels and depression.METHODS :Participants were type 1 diabetic adolescents,with a mean age = 12.5 years(23 females and 16 males),seen at a northwest suburban Chicago hospital.The sample population was free of comorbid clinical health conditions.Subjects completed a three-part neuropsychological battery including the Digit Symbol Task,Trail Making Test,and Controlled Oral Word Association test.Following each task,individuals rated task difficulty and then completed a depression inventory.Performance on these three tests is reflective of neuropsychological status in relation to glucose control.Blood glucose levels were measured immediately prior to and after completing the neuropsychological battery using a glucose meter.Hb A1 c levels were obtained from medical records.Academic performance was based on self-reported grades in Math,Science,and English.Data was analyzed using multiple regression models to evaluate the associations between academic performance,perception of task difficulty,and glucose control.RESULTS:Perceptions of difficulty on a neuropsychological battery significantly predicted academic performance after accounting for glucose control and depression.Perceptions of difficulty on the neuropsychological tests were inversely correlated with academic performance(r =-0.48),while acute(blood glucose) and long-term glucose levels increased along with perceptions of task difficulty(r = 0.47).Additionally,higher depression scores were associatedwith poorer academic performance(r =-0.43).With the first regression analysis,perception of difficulty on the neuropsychological tasks contributed to 8% of the variance in academic performance after controlling for peripheral blood glucose and depression.In the second regression analysis,perception of difficulty accounted for 11% of the variance after accounting for academic performance and depression.The final regression analysis indicated that perception of difficulty increased with peripheral blood glucose,contributing to 22% of the variance.Most importantly,after controlling for perceptions of task difficulty,academic performance no longer predicted glucose levels.Finally,subjects who found the cognitive battery difficult were likely to have poor academic grades.CONCLUSION:Perceptions of difficulty on neurological tests exhibited a significant association with academic achievement,indicating that deficits in this skill may lead to academic disadvantage in diabetic patients.

Understanding the link between type 2 diabetes mellitus and Parkinson's disease:role of brain insulin resistance

Type 2 diabetes mellitus and Parkinson's disease are chronic diseases linked to a growing pandemic that affects older adults and causes significant socio-economic burden.Epidemiological data supporting a close relationship between these two aging-related diseases have resulted in the investigation of shared pathophysiological molecular mechanisms.Impaired insulin signaling in the brain has gained increasing attention during the last decade and has been suggested to contribute to the development of Parkinson's disease through the dysregulation of several pathological processes.The contribution of type 2 diabetes mellitus and insulin resistance in neurodegeneration in Parkinson's disease,with emphasis on brain insulin resistance,is extensively discussed in this article and new therapeutic strategies targeting this pathological link are presented and reviewed.

Risk factors and a predictive model of diabetic foot in hospitalized patients with type 2 diabetes

BACKGROUND The risk factors and prediction models for diabetic foot(DF)remain incompletely understood,with several potential factors still requiring in-depth investigations.AIM To identify risk factors for new-onset DF and develop a robust prediction model for hospitalized patients with type 2 diabetes.METHODS We included 6301 hospitalized patients with type 2 diabetes from January 2016 to December 2021.A univariate Cox model and least absolute shrinkage and selection operator analyses were applied to select the appropriate predictors.Nonlinear associations between continuous variables and the risk of DF were explored using restricted cubic spline functions.The Cox model was further employed to evaluate the impact of risk factors on DF.The area under the curve(AUC)was measured to evaluate the accuracy of the prediction model.RESULTS Seventy-five diabetic inpatients experienced DF.The incidence density of DF was 4.5/1000 person-years.A long duration of diabetes,lower extremity arterial disease,lower serum albumin,fasting plasma glucose(FPG),and diabetic nephropathy were independently associated with DF.Among these risk factors,the serum albumin concentration was inversely associated with DF,with a hazard ratio(HR)and 95%confidence interval(CI)of 0.91(0.88-0.95)(P<0.001).Additionally,a U-shaped nonlinear relationship was observed between the FPG level and DF.After adjusting for other variables,the HRs and 95%CI for FPG<4.4 mmol/L and≥7.0 mmol/L were 3.99(1.55-10.25)(P=0.004)and 3.12(1.66-5.87)(P<0.001),respectively,which was greater than the mid-range level(4.4-6.9 mmol/L).The AUC for predicting DF over 3 years was 0.797.CONCLUSION FPG demonstrated a U-shaped relationship with DF.Serum albumin levels were negatively associated with DF.The prediction nomogram model of DF showed good discrimination ability using diabetes duration,lower extremity arterial disease,serum albumin,FPG,and diabetic nephropathy(Clinicaltrial.gov NCT05519163).

Isletβ-cell function preservation by different anti-diabetic treatments in Chinese elderly patients with type 2 diabetes mellitus

BACKGROUND The preservation of isletβ-cell function in elderly patients with type 2 diabetes mellitus(T2DM)is a top priority for diabetic control.AIM To assess the preservation of isletβ-cell function among elderly Chinese patients with T2DM after different anti-diabetic treatments.METHODS In this longitudinal observational study,elderly patients with T2DM treated with insulin,oral antidiabetic drugs or a combination of both were enrolled to disclose their isletβ-cell function between baseline and follow-up.Isletβ-cell function was determined by the plasma Homeostasis Model forβ-cell function(HOMA-β),Cpeptide and area under the curve(AUC)based on oral glucose tolerance test.Changes inβ-cell function(decrement or increment from baseline)between different therapy groups were the outcomes.RESULTS In total,745 elderly patients(≥60 years)with T2DM[insulin monotherapy,n=105;oral anti-diabetic drugs(OAD)monotherapy,n=321;insulin plus OAD,n=319]had their baseline and follow-upβ-cell function assessed during a median observation period of 4.5 years(range,3.0-7.2 years).Overall,isletβ-cell function(HOMA-β,fasting Cpeptide,fasting insulin,AUCc-pep,AUCins,AUCc-pep/AUCglu,AUCins/AUCglu)consistently deteriorated over time regardless of the three different antidiabetic treatments.No statistical differences in decrement were observed among the three groups regarding the isletβ-cell function indices.All three groups showed an increased ratio of delayed insulin secretion response after 4.5 years of observation.CONCLUSION In Chinese elderly patients with T2DM,isletβ-cell function progressively declines regardless of insulin supplement or insulin plus OAD treatments.

Effect of SPTLC1 on type 2 diabetes mellitus

BACKGROUND Although numerous single nucleotide polymorphism in multiple genes involve in the risk of type 2 diabetes mellitus(T2D),the single gene defects of T2D with strong family history is not clear yet.SPTLC1 are causative for hereditary sensory and autonomic neuropathy,which is clinical overlapping with diabetic peripheral neuropathy.Mice with adipocyte-specific deletion of SPTLC1 had impaired glucose tolerances and insulin sensitivity.Thus,it is necessary to investigate the SPTLC1 mutations in adult-onset T2D with strong family history.AIM To analyze the role of SPTLC1 mutation on adult-onset T2D with strong family history.METHODS By whole-exome sequence analysis of a patient with T2D and his family members,an uncertain variant in SPTLC1 was identified.Bioinformation analysis was used to evaluate the influence of mutation,rare variant gene-level associations for SPTLC1 in T2D,and the relationship between SPTLC1 mRNA and T2D in human islets from GSE25724.The effect of G371R of SPTLC1 on the characteristics of inflammatory cytokines and apoptosis was also tested on human embryonic kidney(HEK)293 cells.RESULTS A single nucleotide variation in SPTLC1(c.1111G>A:p.G371R)was identified in a family with T2D.The deleterious variant was predicted by functional analysis through hidden Markov models and mendelian clinically applicable pathogenicity software.This pathogenicity might be derived from the different amino acid properties.In HEK 293T cells,p.G371R of SPTLC1 induced the expression of tumor necrosis factor-αand the percent of apoptosis.Meanwhile,rare variant gene-level associations for SPTLC1 also refer to the high risk of T2D(the overall odds ratio=2.4968,P=0.0164).Data from GSE25724 showed that SPTLC1 mRNA was lower in pancreatic islets from T2D human islets(P=0.046),and was as sociated with the decreased level of insulin mRNA expression(Spearman r=0.615,P=0.025).CONCLUSION The study classified SPTLC1 p.G371R mutation as the likely pathogenic mutation from an adult-onset T2D patients with strong family history T2D.

Insulin autoantibodies,D-dimer and microalbuminuria:A crosssectional,case-control study of type 2 diabetes

BACKGROUND Type 2 diabetes mellitus(T2DM)often leads to vascular complications,such as albuminuria.The role of insulin autoantibodies(IAA)and their interaction with D-dimer in this context remains unclear.AIM To investigate the characteristics of IAA and its effect on albuminuria in T2DM patients.METHODS We retrospectively analyzed clinical data from 115 T2DM patients with positive IAA induced by exogenous insulin,and 115 age-and sex-matched IAA-negative T2DM patients as controls.Propensity scores were calculated using multivariate logistic regression.Key variables were selected using the least absolute shrinkage and selection operator(LASSO)algorithm.We constructed a prediction model and analyzed the association between IAA and albuminuria based on demographic and laboratory parameters.RESULTS The IAA-positive group had significantly higher D-dimer levels[0.30(0.19-0.55)mg/L vs 0.21(0.19-0.33)mg/L,P=0.008]and plasma insulin levels[39.1(12.0-102.7)μU/mL vs 9.8(5.5-17.6)μU/mL,P<0.001]compared to the IAA-negative group.Increases in the insulin dose per weight ratio,diabetes duration,and urinary albumin-to-creatinine ratio(UACR)were observed but did not reach statistical significance.The LASSO model identified plasma insulin and D-dimer as key factors with larger coefficients.D-dimer was significantly associated with UACR in the total and IAA-positive groups but not in the IAA-negative group.The odds ratio for D-dimer elevation(>0.5 g/L)was 2.88(95%confidence interval:1.17-7.07)in the IAA-positive group(P interaction<0.05).CONCLUSION D-dimer elevation is an independent risk factor for abnormal albuminuria and interacts with IAA in the development of abnormal albuminuria in T2DM patients.

DNA methylation in the association between pesticide exposures and type 2 diabetes

BACKGROUND Numerous epidemiological studies have found that pesticide exposure is associated with the incidence of type 2 diabetes(T2D);however,the underlying mechanisms remain unknown.DNA methylation may play a role in this process.AIM To identify the genes associated with pesticide exposure and T2D by reviewing the current literature.METHODS We systematically searched PubMed and Embase for relevant studies that examined the association between pesticide exposure and DNA methylation,and studies on DNA methylation and T2D through January 15,2024.RESULTS We identified six genes(Alu,CABLES1,CDH1,PDX1,PTEN,PTPRN2)related to pesticide exposure and T2D.We also suggested future research directions to better define the role of DNA methylation in the association between pesticide exposure and T2D.CONCLUSION DNA methylation of specific genes may play a vital role in the association between pesticide exposure and T2D.

Investigating the impact of intestinal glucagon-like peptide-1 on hypoglycemia in type 1 diabetes

Recent advances in understanding type 1 diabetes(T1D)highlight the complexity of managing hypoglycemia,a frequent and perilous complication of diabetes therapy.This letter delves into a novel study by Jin et al,which elucidates the role of intestinal glucagon-like peptide-1(GLP-1)in the counterregulatory response to hypoglycemia in T1D models.The study employed immunofluorescence,Western blotting,and enzyme-linked immunosorbent assay to track changes in GLP-1 and its receptor expression in diabetic mice subjected to recurrent hypoglycemic episodes.Findings indicate a significant increase in intestinal GLP-1 and GLP-1 receptor expression,correlating with diminished adrenal and glucagon responses,crucial for glucose stabilization during hypoglycemic events.This letter aims to explore the implications of these findings for future therapeutic strategies and the broader understanding of T1D management.

Classification and identification of risk factors for type 2 diabetes

The risk factors for type 2 diabetes mellitus(T2DM)have been increasingly researched,but the lack of systematic identification and categorization makes it difficult for clinicians to quickly and accurately access and understand all the risk factors,which are categorized in this paper into five categories:Social determinants,lifestyle,checkable/testable risk factors,history of illness and medication,and other factors,which are discussed in a narrative review.Meanwhile,this paper points out the problems of the current research,helps to improve the systematic categorisation and practicality of T2DM risk factors,and provides a professional research basis for clinical practice and industry decision-making.

Correlation between diabetic peripheral neuropathy and thyroid hormone sensitivity in elderly patients with type 2 diabetes mellitus

BACKGROUND Diabetic peripheral neuropathy(DPN)is a common complication of type 2 diabetes mellitus(T2DM),significantly affecting patients’quality of life and imposing a substantial economic burden.Recent studies have highlighted the role of thyroid hormones in diabetes complications,particularly in elderly patients with T2DM.However,the relationship between thyroid hormone sensitivity and DPN remains unclear.AIM To investigate the correlation between thyroid hormone sensitivity and DPN in elderly patients with T2DM.METHODS In a cohort of 256 elderly patients with T2DM,propensity score matching was used to balance age,sex,and diabetes duration.Clinical data were collected to calculate thyroid hormone sensitivity and analyze its correlation with DPN.A random forest model was used to evaluate the diagnostic value of free triiodothyronine/free thyroxine(FT_(3)/FT_(4))for DPN.RESULTS Patients with DPN had a lower FT_(3)/FT_(4) ratio[(0.302±0.053)vs(0.316±0.049),P=0.040].Quartile stratification showed decreasing DPN prevalence with higher FT_(3)/FT_(4) ratios.Spearman’s correlation analysis showed that a lower FT_(3)/FT_(4) ratio was associated with higher glycated hemoglobin,fasting blood glucose,reduced nerve conduction velocity,and electrical skin conductance.Logistic regression indicated a positive relationship between the median FT_(3)/FT_(4) ratio and bilateral foot electrochemical skin conductance[odds ratio(OR):1.019;95%CI:1.005-1.034;P=0.007]and sural nerve sensory amplitude(OR:1.310;95%CI:1.008-1.703;P=0.043).Receiver operating characteristic analysis using a random forest model showed that incorporating FT_(3)/FT_(4) improved predictive performance for DPN,with an area under the curve of 0.74,sensitivity of 0.79,specificity of 0.64,and accuracy of 0.77.CONCLUSION In elderly patients with T2DM with euthyroidism,a lower FT_(3)/FT_(4) ratio is correlated with increased DPN incidence,affecting both large and small nerve fibers.FT_(3)/FT_(4) is an effective predictor of DPN.

Electroacupuncture relieves type 2 diabetes by regulating gut microbiome

Cumulative studies have shown that the composition of the gut microbiome is strongly associated with the development of type 2 diabetes mellitus(T2DM).Electroacupuncture(EA)therapy has been reported to alleviate various diseases,including T2DM,by targeting specific acupuncture points and regulating metabolic homeostasis.A recent review published in the World Journal of Diabetes detailed the role of the gut microbiome in T2DM,discussing the role of therapeutic strategies developed to alleviate T2DM and its complications based on gut microbiome in ameliorating T2DM,as well as the effects of multiple diabetes medications on gut microbiome.However,the review did not elucidate the therapeutic role of EA therapy,a common non-pharmacological intervention for T2DM.This letter complemented the effect of EA therapy on glucose metabolism by adjusting the gut microbiome composition,which reveals the underlying mechanism of glucose lowering by EA therapy and provides a scientific basis for the application of EA therapy in clinical treatment.

Triglyceride-glucose related indices as predictors for major adverse cardiovascular events and overall mortality in type-2 diabetes mellitus patients

BACKGROUND Recent studies have indicated that triglyceride glucose(TyG)-waist height ratio(WHtR)and TyG-waist circumference(TyG-WC)are effective indicators for evaluating insulin resistance.However,research on the association in TyG-WHtR,TyG-WC,and the risk and prognosis of major adverse cardiovascular events(MACEs)in type 2 diabetes mellitus(T2DM)cases are limited.AIM To clarify the relation in TyG-WHtR,TyG-WC,and the risk of MACEs and overall mortality in T2DM patients.METHODS Information for this investigation was obtained from Action to Control Cardiovascular Risk in Diabetes(ACCORD)/ACCORD Follow-On(ACCORDION)study database.The Cox regression model was applied to assess the relation among TyG-WHtR,TyG-WC and future MACEs risk and overall mortality in T2DM cases.The RCS analysis was utilized to explore the nonlinear correlation.Subgroup and interaction analyses were conducted to prove the robustness.The receiver operating characteristic curves were applied to analysis the additional predicting value of TyG-WHtR and TyG-WC.RESULTS After full adjustment for confounding variables,the highest baseline TyG-WHtR cohort respectively exhibited a 1.353-fold and 1.420-fold higher risk for MACEs and overall mortality,than the lowest quartile group.Similarly,the highest baseline TyG-WC cohort showed a 1.314-fold and 1.480-fold higher risk for MACEs and overall mortality,respectively.Each 1 SD increase in TyG-WHtR was significantly related to an 11.7%increase in MACEs and a 14.9%enhance in overall mortality.Each 1 SD increase in TyG-WC corresponded to an 11.5%in MACEs and a 16.6%increase in overall mortality.Including these two indexes in conventional models significantly improved the predictive power for MACEs and overall mortality.CONCLUSION TyG-WHtR and TyG-WC were promising predictors of MACEs and overall mortality risk in T2DM cases.

Association between serum retinol-binding protein and lower limb atherosclerosis risk in type 2 diabetes mellitus

BACKGROUND Serum retinol-binding protein(RBP)is the primary transport protein of circulating vitamin A.RBP has a crucial role in maintaining nutrient metabolism and physiologic homeostasis.Several studies have indicated that serum RBP participates in the progression of diabetes and diabetes-related complications.However,the impact of serum RBP on lower limb atherosclerosis has not been determined in individuals with type 2 diabetes mellitus(T2DM).AIM To determine the association between serum RBP and lower limb atherosclerosis in individuals with T2DM.METHODS This retrospective study enrolled 4428 eligible T2DM patients and divided the patients into non-lower limb atherosclerosis(n=1913)and lower limb atherosclerosis groups(n=2515)based on lower limb arterial ultrasonography results.At hospital admission,baseline serum RBP levels were assessed,and all subjects were categorized into three groups(Q1-Q3)based on RBP tertiles.Logistic regression,restricted cubic spline regression,subgroup analysis,and machine learning were used to assess the association between RBP levels and lower limb atherosclerosis risk.RESULTS Among 4428 individuals with T2DM,2515(56.80%)had lower limb atherosclerosis.Logistic analysis showed that lower limb atherosclerosis risk increased by 1%for every 1 unit rise in serum RBP level(odds ratio=1.01,95%confidence interval:1.00-1.02,P=0.004).Patients in the highest tertile group(Q3)had a higher lower limb atherosclerosis risk compared to the lowest tertile group(Q1)(odds ratio=1.36,95%confidence interval:1.12-1.67,P=0.002).The lower limb atherosclerosis risk gradually increased with an increase in RBP tertile(P for trend=0.005).Restricted cubic spline analysis indicated a linear correlation between serum RBP levels and lower limb atherosclerosis risk(non-linear P<0.05).Machine learning demonstrated the significance and diagnostic value of serum RBP in predicting lower limb atherosclerosis risk.CONCLUSION Elevated serum RBP levels correlate with an increased lower limb atherosclerosis risk in individuals with T2DM.

Clinical significance of Ki-67 in patients with lung adenocarcinoma in situ complicated by type 2 diabetes

BACKGROUND The increasing number of type 2 diabetes mellitus(T2DM)patients leads to higher rates of morbidity and mortality related to lung cancer.AIM To investigate the utility of the proliferating cell nuclear antigen Ki-67 in patients with lung adenocarcinoma in situ(AIS)complicated by T2DM.METHODS One hundred patients with AIS and T2DM(group A),100 patients with AIS alone(group B),and 60 patients with benign lung lesions(group C)admitted to the Department of Thoracic Surgery and Endocrinology of the First Affiliated Hospital of Soochow University from November 2021 to December 2022 were enrolled.Ki-67 expression was compared among the groups.RESULTS Group A had significantly higher levels of fasting plasma glucose(FPG),total cholesterol(TC),total triglyceride,low-density lipoprotein cholesterol,glycosylated hemoglobin(HbA1c),and insulin than groups B and C(P<0.01).Meanwhile,group B had higher insulin levels than group C(P<0.01).Group A exhibited a significantly higher average Ki-67 positivity rate than group B(P<0.01).The Ki-67 positivity rate in group A was 86.87%,while the positivity rate in group B was 77%.Ki-67 was positively correlated with FPG(P<0.01)and HbA1c levels(P<0.01).Ki-67,FBG,insulin,HbA1c,high-density lipoprotein cholesterol and TC were independent factors for patients with AIS complicated by T2DM.Chen K et al.Ki67 in patients with AIS complicated by T2DM WJD https://www.wjgnet.com 2 February 15,2025 Volume 16 Issue 2 CONCLUSION Ki-67 expression was higher in patients with AIS complicated by T2DM than in patients with AIS alone.Therefore,detecting the Ki-67 level might assist in the diagnosis of AIS in patients with T2DM.

Glucagon-like peptide-1 and impaired counterregulatory responses to hypoglycemia in type 1 diabetes

This letter comments on a study by Jin et al,published recently in the World Journal of Diabetes.Hypoglycemia is a significant complication of diabetes,with primary defense mechanisms involving the stimulation of glucagon secretion inα-cells and the inhibition of insulin secretion in pancreaticβ-cells,which are often compromised in type 1 diabetes mellitus(T1DM)and advanced type 2 diabetes mellitus.Recurrent hypoglycemia predisposes the development of impaired hypoglycemia awareness,a condition underpinned by complex pathophysiological processes,encompassing central nervous system adaptations and several hormonal interactions,including a potential role for glucagon-like peptide-1(GLP-1)in paracrine and endocrine vias.Experimental evidence indicates that GLP-1 may impair hypoglycemic counterregulation by disrupting the sympathoadrenal system and promoting somatostatin release in pancreaticδ-cells,which inhibits glucagon secretion from neighboringα-cells.However,current trials evaluating GLP-1 receptor agonists(GLP-1 RAs)in T1DM patients have shown promising benefits in reducing insulin requirements and body weight,without increasing the risk of hypoglycemia.Further research is essential to elucidate the specific roles of GLP-1 and GLP-1 RAs in modulating glucagon secretion and the sympathetic-adrenal reflex,and their impact on hypoglycemia unawareness in T1DM patients.

Plantamajoside improves type 2 diabetes mellitus pancreaticβ-cell damage by inhibiting endoplasmic reticulum stress through Dnajc1 up-regulation

BACKGROUND Plantamajoside(PMS)has shown potential in mitigating cell damage caused by high glucose(HG)levels.Despite this,the precise therapeutic effects of PMS on type 2 diabetes mellitus(T2DM)and the underlying regulatory mechanisms require further exploration.AIM To investigate PMS therapeutic effects on T2DM in mice and elucidate its mechanisms of action through in vivo and in vitro experiments.METHODS An in vitro damage model of MIN6 cells was established using HG and palmitic acid(PA).PMS's protective effect on cell damage was assessed.Next,transcriptomics was employed to examine how PMS treatment affects gene expression of MIN6 cells.Furthermore,the effect of PMS on protein processing in endoplasmic reticulum and apoptosis pathways was validated.A T2DM mouse model was used to validate the therapeutic effects and mechanisms of PMS in vivo.RESULTS PMS intervention ameliorated cell injury in HG+PA-induced MIN6 cell damage.Transcriptomic analysis revealed that protein processing in the endoplasmic reticulum and apoptosis pathways were enriched in cells treated with PMS,with significant downregulation of the gene Dnajc1.Further validation indicated that PMS significantly inhibited the expression of apoptosis-related factors(Bax,CytC)and endoplasmic reticulum stress(ERS)-related factors[ATF6,XBP1,Ddit3(CHOP),GRP78],while promoting the expression of Bcl-2 and Dnajc1.Additionally,the inhibitory effects of PMS on ERS and apoptosis were abolished upon Dnajc1 silencing.Furthermore,in vivo experiments demonstrated that PMS intervention effectively improved pancreatic damage,suppressed the expression of apoptosis-related factors(Bax,CytC),and ERS-related factors[ATF6,XBP1,Ddit3(CHOP),GRP78],while promoting the expression of Bcl-2 and Dnajc1 in a T2DM model mice.CONCLUSION PMS intervention could alleviate pancreatic tissue damage effectively.The mechanism of action involves Dnajc1 activation,which subsequently inhibits apoptosis and ERS,ameliorating damage to pancreaticβ-cells.

High metabolic dysfunction-associated steatotic liver disease prevalence in type 2 diabetes: Urgent need for integrated screening and lifestyle intervention

This letter discusses the recent study by Mukherjee et al,which identifies a significant prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)among newly diagnosed type 2 diabetes mellitus(T2DM)patients in Bihar,India,and underscores the pressing need for integrated MASLD mana-gement within T2DM care.With 72.3%of the study cohort affected by MASLD,implementing routine liver function tests and ultrasound screenings is recom-mended as a standard practice in diabetes care,especially in regions with high prevalence rates.The study also advocates for dietary and lifestyle modifications,particularly the reduction of saturated fats,to slow MASLD progression.Patient education on monitoring body mass index and waist circumference,coupled with the integration of these metrics into digital health records,could enhance patient involvement and support proactive health management.Moreover,the letter emphasizes the advantages of developing a region-specific MASLD risk model that incorporates local dietary patterns and socioeconomic factors.Continued research into genetic and environmental determinants of MASLD remains es-sential for advancing our understanding of its etiology and informing targeted public health strategies.

Correlation of periodontal inflamed surface area with glycated hemoglobin,interleukin-6 and lipoprotein(a)in type 2 diabetes with retinopathy

BACKGROUND The two-way relationship between periodontitis and type 2 diabetes mellitus(T2DM)is well established.Prolonged hyperglycemia contributes to increased periodontal destruction and severe periodontitis,accentuating diabetic complications.An inflammatory link exists between diabetic retinopathy(DR)and periodontitis,but the studies regarding this association and the role of lipoprotein(a)[Lp(a)]and interleukin-6(IL-6)in these conditions are scarce in the literature.AIM To determine the correlation of periodontal inflamed surface area(PISA)with glycated Hb(HbA1c),serum IL-6 and Lp(a)in T2DM subjects with retinopathy.METHODS This cross-sectional study comprised 40 T2DM subjects with DR and 40 T2DM subjects without DR.All subjects were assessed for periodontal parameters[bleeding on probing(BOP),probing pocket depth,clinical attachment loss(CAL),oral hygiene index-simplified,plaque index(PI)and PISA],and systemic parameters[HbA1c,fasting plasma glucose and postprandial plasma glucose,fasting lipid profile,serum IL-6 and serum Lp(a)].RESULTS The proportion of periodontitis in T2DM with and without DR was 47.5%and 27.5%respectively.Severity of periodontitis,CAL,PISA,IL-6 and Lp(a)were higher in T2DM with DR group compared to T2DM without DR group.Significant difference was observed in the mean percentage of sites with BOP between T2DM with DR(69%)and T2DM without DR(41%),but there was no significant difference in PI(P>0.05).HbA1c was positively correlated with CAL(r=0.351,P=0.001),and PISA(r=0.393,P≤0.001)in study subjects.A positive correlation was found between PISA and IL-6(r=0.651,P<0.0001);PISA and Lp(a)(r=0.59,P<0.001);CAL and IL-6(r=0.527,P<0.0001)and CAL and Lp(a)(r=0.631,P<0.001)among study subjects.CONCLUSION Despite both groups having poor glycemic control and comparable plaque scores,the periodontal parameters were higher in DR as compared to T2DM without DR.Since a bidirectional link exists between periodontitis and DM,the presence of DR may have contributed to the severity of periodontal destruction and periodontitis may have influenced the progression of DR.

Sodium-dependent glucose transporter 2 inhibitors effects on myocardial function in patients with type 2 diabetes and asymptomatic heart failure

BACKGROUND Sodium-dependent glucose transporter 2 inhibitors(SGLT2i)have shown efficacy in reducing heart failure(HF)burden in a very heterogeneous groups of patients,raising doubts about some contemporary assumptions of their mechanism of action.We previously published a prospective observational study that evaluated mechanisms of action of SGLT2i in patients with type 2 diabetes who were in HF stages A and B on dual hypoglycemic therapy.Two groups of patients were included in the study:the ones receiving SGLT2i as an add-on agent to metformin and the others on dipeptidyl peptidase-4 inhibitors as an add-on to metformin due to suboptimal glycemic control.AIM To evaluate the outcomes regarding natriuretic peptide,oxidative stress,inflammation,blood pressure,heart rate,cardiac function,and body weight.METHODS The study outcomes were examined by dividing each treatment arm into two subgroups according to baseline parameters of global longitudinal strain(GLS),N-terminal pro-brain natriuretic peptide,myeloperoxidase(MPO),high-sensitivity C-reactive protein(hsCRP),and systolic and diastolic blood pressure.To evaluate the possible predictors of observed changes in the SGLT2i arm during follow-up,a rise in stroke volume index,body mass index(BMI)decrease,and lack of heart rate increase,linear regression analysis was performed.RESULTS There was a greater reduction of MPO,hsCRP,GLS,and blood pressure in the groups with higher baseline values of mentioned parameters irrespective of the therapeutic arm after 6 months of follow-up.Significant independent predictors of heart rate decrease were a reduction in early mitral inflow velocity to early diastolic mitral annular velocity at the interventricular septal annulus ratio and BMI,while the predictor of stroke volume index increase was SGLT2i therapy itself.CONCLUSION SGLT2i affect body composition,reduce cardiac load,improve diastolic/systolic function,and attenuate the sympathetic response.Glycemic control contributes to the improvement of heart function,blood pressure control,oxidative stress,and reduction in inflammation.