Poorly controlled type Ⅱ diabetes mellitus significantly enhances postoperative chemoresistance in patients with stage Ⅲ colon cancer

BACKGROUND Type Ⅱ diabetes mellitus(T2DM)has been associated with increased risk of colon cancer(CC)and worse prognosis in patients with metastases.The effects of T2DM on postoperative chemoresistance rate(CRR)and long-term disease-free survival(DFS)and overall survival(OS)in patients with stage Ⅲ CC who receive curative resection remain controversial.AIM To investigate whether T2DM or glycemic control is associated with worse postoperative survival outcomes in stage Ⅲ CC.METHODS This retrospective cohort study included 278 patients aged 40-75 years who underwent surgery for stage Ⅲ CC from 2018 to 2021.Based on preoperative T2DM history,the patients were categorized into non-DM(n=160)and DM groups(n=118).The latter was further divided into well-controlled(n=73)and poorly controlled(n=45)groups depending on the status of glycemic control.DFS,OS,and CRR were compared between the groups and Cox regression analysis was used to identify risk factors.RESULTS Patients in the DM and non-DM groups demonstrated similar DFS,OS,and CRR(DFS:72.03%vs 78.75%,P=0.178;OS:81.36%vs 83.12%,P=0.638;CRR:14.41%vs 7.5%,P=0.063).Poorly controlled DM was associated with a significantly worse prognosis and higher CRR than well-controlled DM(DFS:62.22%vs 78.07%,P=0.021;OS:71.11%vs 87.67%,P=0.011;CRR:24.40%vs 8.22%,P=0.015).High preoperative fasting plasma glucose[DFS:Hazard ratio(HR)=2.684,P<0.001;OS:HR=2.105,P=0.019;CRR:HR=2.214,P=0.005]and glycosylated hemoglobin levels(DFS:HR=2.344,P=0.006;OS:HR=2.119,P=0.021;CRR:HR=2.449,P=0.009)indicated significantly poor prognosis and high CRR,while T2DM history did not(DFS:HR=1.178,P=0.327;OS:HR=0.933,P=0.739;CRR:HR=0.997,P=0.581).CONCLUSION Increased preoperative fasting plasma glucose and glycosylated hemoglobin levels,but not T2DM history,were identified as risk factors associated with poor postoperative outcomes and high CRR in patients with stage Ⅲ CC.

Application of Dorzagliatin in peritoneal dialysis patients with type 2 diabetes mellitus:A case report

BACKGROUND Treating diabetes in dialysis patients remains a challenge,with many hypoglycemic drugs requiring dose adjustments or avoidance in these patients.CASE SUMMARY This report describes an 83-year-old female patient with a 30-year history of type 2 diabetes(T2DM)who had struggled to control her blood sugar for more than a year.She had a history of high blood pressure for 30 years,had undergone continuous ambulatory peritoneal dialysis for more than two years,was 163 cm tall,weighed 77 kg,and had a body mass index of 28.98 kg/m2.Despite intensive insulin therapy at a daily dose of 150 units,adding Dorzagliatin at a dosage of 75 mg orally twice daily led to immediate blood sugar improvement and a gradual reduction in insulin dosage.After one month of follow-up,the fasting plasma glucose was 6-8 mmol/L,and the 2-hour postprandial glucose was 8-12 mmol/L.CONCLUSION To our knowledge,this report is the first to use Dorzagliatin to treat type 2 diabetes peritoneal dialysis patients with challenging glucose control.Dorzagliatin,a novel glucokinase activator primarily metabolized by the liver,exhibits no pharmacokinetic differences among patients with varying degrees of chronic kidney disease.It has a high plasma protein binding rate and may not be cleared by peritoneal dialysis,potentially offering a new glycemic control option for Type 2 diabetic patients on peritoneal dialysis.

Unveiling mitochondrial mysteries:Exploring novel tRNA variants in type 2 diabetes mellitus

The recent study of Ding et al provides valuable insights into the functional implications of novel mitochondrial tRNATrp and tRNASer(AGY)variants in type 2 diabetes mellitus(T2DM).This editorial explores their findings,highlighting the role of mitochondrial dysfunction in the pathogenesis of T2DM.By examining the molecular mechanisms through which these tRNA variants contribute to disease progression,the study introduces new targets for therapeutic strategies.We discuss the broader implications of these results,emphasizing the importance of understanding mitochondrial genetics in addressing T2DM.

Intestinal glucagon-like peptide-1:A new regulator of impaired counterregulatory responses to hypoglycemia in type 1 diabetes mellitus

In this article,we review the study by Jin et al,which examined the role of intestinal glucagon-like peptide-1(GLP-1)in counterregulatory responses to hypoglycemia in patients with type 1 diabetes mellitus(T1DM).With the global rise of T1DM,there is an increased burden on society and healthcare systems.Due to insulin therapy and islet dysfunction,T1DM patients are highly vulnerable to severe hypoglycemia,a leading cause of mortality.In healthy individuals,counterregulatory mechanisms restore blood glucose during hypoglycemia,but repeated episodes impair these responses.Jin et al demonstrated that overexpression of GLP-1 attenuates the sympathetic-adrenal reflex and disrupts the secretion of counterregulatory hormones such as glucagon during hypoglycemia,leading to counterregulatory dysfunction.These findings highlight the critical role of GLP-1 in the impaired counterregulatory response to hypoglycemia in T1DM patients and provide new insights into the potential application of GLP-1-related therapies in T1DM patients.

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.

Risk factors of developing non-arteric ischemic optic neuropathy in patients with type 2 diabetes mellitus:a single-center retrospective cohort study

AIM:To determine the risk factors and time to non-arteric ischemic optic neuropathy(NAION)occurrence among Thai type 2 diabetes mellitus(T2DM)patients.METHODS:A retrospective review of 266 newly diagnosed T2DM cases at Rajavithi Hospital between 2007 and 2016 was conducted to determine time to occurrence of NAION and evaluate associated risk factors.RESULTS:Hypertension and dyslipidemia were the most common pre-existing vascular diseases and there was a significant male predominance in the NAION group.The mean age of the NAION group was significantly higher than that of the group without NAION.A higher proportion of subjects in the NAION group had hypertension,dyslipidemia,high diastolic blood pressure,smokers,and had a small cup-to-disc ratio(CDR).Higher levels of triglycerides and lowdensity lipoprotein-cholesterol in the group with NAION.Fiftyfive patients among 266 participants(20.68%)developed NAION during a mean follow-up time of 81.26±25.04mo.In a multivariable logistic regression analysis,dyslipidemia(OR=8.36,95%CI,3.447–20.273,P<0.001),high low density lipoprotein levels(OR=1.017,95%CI,1.004–1.029,P=0.009),and small CDR(OR=11.92,95%CI,4.477–31.741,P<0.001)were significant risk factors for NAION development.Smoking was the strongest predictive risk(OR=12.843,95%CI,3.959–41.659,P<0.001).Vascular complications of T2DM and aspirin were not associated with NAION.CONCLUSION:T2DM patients with dyslipidemia or a small CDR should be carefully followed up as they are at increased risk of developing NAION.

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.

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.

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.

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.

Gestational diabetes mellitus combined with fulminant type 1 diabetes mellitus, four cases of double diabetes: A case report

BACKGROUND Fulminant type 1 diabetes mellitus(FT1DM)that occurs during pregnancy or the perinatal period is known as pregnancy-related FT1DM(PF),always without history of abnormal glucose metabolism.Here,we present four patients who developed FT1DM during treatment but were first diagnosed with gestational diabetes mellitus(GDM).CASE SUMMARY The clinical data of four patients with GDM combined with FT1DM admitted to our hospital between July 2018 and April 2021 were collected,and the patients and their infants were followed up.All patients were diagnosed with GDM during the second trimester and were treated.The blood glucose level elevated suddenly during the third trimester and then were diagnosed with FT1DM.Two patients had an insulin allergy,and two had symptoms of upper respiratory tract infection before onset.One patient developed ketoacidosis,and three developed ketosis.Two patients had cesarean section deliveries,and two had vaginal deliveries.The growth and development of the infants were normal.C-peptide levels were lower than those at onset,suggesting progressive impairment of islet function.The frequencies of the DRB109:01,DQB103:03,DQA103:02,DPA101:03,DPA102:02,DPB105:01,DRB401:03,G 01:01,and G 01:04 human leukocyte antigen(HLA)-G alleles were high in the present study.CONCLUSION In comparison with pregnancy-associated FT1DM(PF),patients with GDM combined with FT1DM had an older age of onset,higher body mass index,slower onset,fewer prodromal symptoms,and less acidosis.The pathogenesis may be due to various factors affecting the already fragileβ-cells of GDM patients with genetically susceptible class II HLA genotypes.We speculate that GDM combined with FT1DM during pregnancy,referred to as“double diabetes,”is a subtype of PF with its own unique characteristics that should be investigated further.

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.

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.

Prevalence and risk factors of diabetes mellitus among elderly patients in the Lugu community

BACKGROUND Age is a significant risk factor of diabetes mellitus(DM).With the develop of population aging,the incidence of DM remains increasing.Understanding the epidemiology of DM among elderly individuals in a certain area contributes to the DM interventions for the local elderly individuals with high risk of DM.AIM To explore the prevalence of DM among elderly individuals in the Lugu community and analyze the related risk factors to provide a valid scientific basis for the health management of elderly individuals.METHODS A total of 4816 elderly people who came to the community for physical examination were retrospectively analyzed.The prevalence of DM among the elderly was calculated.The individuals were divided into a DM group and a non-DM group according to the diagnosis of DM to compare the differences in diastolic blood pressure(DBP)and systolic blood pressure(SBP),fasting blood glucose,body mass index(BMI),waist-to-hip ratio(WHR)and incidence of hypertension(HT),coronary heart disease(CHD),and chronic kidney disease(CKD).RESULTS DM was diagnosed in 32.70%of the 4816 elderly people.The BMI of the DM group(25.16±3.35)was greater than that of the non-DM group(24.61±3.78).The WHR was 0.90±0.04 in the non-DM group and 0.90±0.03 in the DM group,with no significant difference.The left SBP and SBP in the DM group were 137.9 mmHg±11.92 mmHg and 69.95 mmHg±7.75 mmHg,respectively,while they were 126.6 mmHg±12.44 mmHg and 71.15 mmHg±12.55 mmHg,respectively,in the non-DM group.These findings indicate higher SBP and lower DBP in DM patients than in those without DM.In the DM group,1274 patients were diagnosed with HT,accounting for 80.89%.Among the 3241 non-DM patients,1743(53.78%)were hypertensive and 1498(46.22%)were nonhypertensive.The DM group had more cases of HT than did the non-DM group.There were more patients with CHD or CKD in the DM group than in the non-DM group.There were more patients who drank alcohol more frequently(≥3 times)in the DM group than in the non-DM group.CONCLUSION Older adults in the Lugu community are at a greater risk of DM.In elderly individuals,DM is closely related to high BMI and HT,CHD,and CKD.Physical examinations should be actively carried out for elderly people to determine their BMI,SBP,DBP,and other signs,and sufficient attention should be given to abnormalities in the above signs before further diagnosis.

Correlation between type 2 diabetes mellitus remission and intrapancreatic fat deposition

BACKGROUND Intrapancreatic fat deposition(IPFD)exerts a significant negative impact on patients with type 2 diabetes mellitus(T2DM),accelerates disease deterioration,and may lead to impairedβ-cell quality and function.AIM To investigate the correlation between T2DM remission and IPFD.METHODS We enrolled 80 abdominally obese patients with T2DM admitted to our institution from January 2019 to October 2023,including 40 patients with weight lossinduced T2DM remission(research group)and 40 patients with short-term intensive insulin therapy-induced T2DM remission(control group).We comparatively analyzed improvements in IPFD[differential computed tomography(CT)values of the spleen and pancreas and average CT value of the pancreas];levels of fasting blood glucose(FBG),2-h postprandial blood glucose(2hPBG),and insulin;and homeostasis model assessment of insulin resistance(HOMA-IR)scores.Correlation analysis was performed to explore the association between T2DM remission and IPFD.RESULTS After treatment,the differential CT values of the spleen and pancreas,FBG,2hPBG,and HOMA-IR in the research group were significantly lower than those before treatment and in the control group,and the average CT value of the pancreas and insulin levels were significantly higher.Correlation analysis revealed that the greater the T2DM remission,the lower the amount of IPFD.

Gestational diabetes mellitus may predispose to metabolic dysfunction-associated steatotic liver disease

The development of type 2 diabetes mellitus is a major contributing factor to the worldwide health burden of metabolic dysfunction-associated steatotic liver disease(MASLD).Insulin resistance,subclinical inflammation,dyslipidemia,obesity,and hypertension are all factors in this reciprocal interaction that contribute to the development of MASLD,which includes hepatocellular carci-noma,advanced fibrosis/cirrhosis,and non-alcoholic steatohepatitis(NASH).A new risk factor for MASLD/NASH that affects the course of the disease independently throughout life is gestational diabetes mellitus(GDM).Women with a history of GDM had a higher chance of developing NASH,according to a recent study that used a large-scale database.Although the precise etiology is yet unknown,temporary disruption of pancreatic beta cell activity during pregnancy may set off systemic inflammation,affecting distant organs including the liver.Early screening and management strategies are crucial in mitigating MASLD progression and preventing adverse cardiovascular events in affected individuals.

Serum tumor markers expression(CA199,CA242,and CEA)and its clinical implications in type 2 diabetes mellitus

BACKGROUND Glucose and lipid metabolic disorder in patients with type 2 diabetes mellitus(T2DM)is associated with the levels of serum tumor markers of the digestive tract,such as cancer antigen(CA)199.Therefore,tumor markers in T2DM are important.AIM To evaluate the expression of serum tumor markers[CA199,CA242,and carcinoembryonic antigen(CEA)]and the clinical implications of the expression in T2DM.METHODS For this observational study conducted at Hefei BOE Hospital,China,we enrolled 82 patients with first-onset T2DM and 51 controls between April 2019 and December 2020.Levels of fasting blood glucose(FBG),tumor markers(CA199,CEA,and CA242),glycosylated hemoglobin(HbA1c),etc.were measured and group index levels were compared.Moreover,FBG and HbA1c levels were correlated with tumor marker levels.Tumor markers were tested for diagnostic accuracy in patients with>9%HbA1c using the receiver operating curve(ROC)curve.RESULTS The T2DM group had high serum FBG,HbA1c,CA199,and CEA levels(P<0.05).A comparative analysis of the two groups based on HbA1c levels(Group A:HbA1c≤9%;Group B:HbA1c>9%)revealed significant differences in CEA and CA199 levels(P<0.05).The areas under the ROC curve for CEA and CA199 were 0.853 and 0.809,respectively.CA199,CEA,and CA242 levels positively correlated with HbA1c(r=0.308,0.426,and 0.551,respectively)and FBG levels(r=0.236,0.231,and 0.298,respectively).CONCLUSION As compared to controls,serum CEA and CA199 levels were higher in patients with T2DM.HbA1c and FBG levels correlated with CA199,CEA,and CA242 levels.Patients with poorly controlled blood sugar must be screened for tumor markers.

Icariin accelerates bone regeneration by inducing osteogenesisangiogenesis coupling in rats with type 1 diabetes mellitus

BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.

Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is observed.However,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is scarce.This study aimed to demonstrate and identify predictors of DM control under the influence of CST.Methods:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM group.The incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM groups.Of the 52 patients with DM,CST was administered in 48 cases.Multivariate logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control improvement.Conclusions:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP diagnosis.CST exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

Clinical study of different prediction models in predicting diabetic nephropathy in patients with type 2 diabetes mellitus

BACKGROUND Among older adults,type 2 diabetes mellitus(T2DM)is widely recognized as one of the most prevalent diseases.Diabetic nephropathy(DN)is a frequent com-plication of DM,mainly characterized by renal microvascular damage.Early detection,aggressive prevention,and cure of DN are key to improving prognosis.Establishing a diagnostic and predictive model for DN is crucial in auxiliary diagnosis.AIM To investigate the factors that impact T2DM complicated with DN and utilize this information to develop a predictive model.METHODS The clinical data of 210 patients diagnosed with T2DM and admitted to the First People’s Hospital of Wenling between August 2019 and August 2022 were retrospectively analyzed.According to whether the patients had DN,they were divided into the DN group(complicated with DN)and the non-DN group(without DN).Multivariate logistic regression analysis was used to explore factors affecting DN in patients with T2DM.The data were randomly split into a training set(n=147)and a test set(n=63)in a 7:3 ratio using a random function.The training set was used to construct the nomogram,decision tree,and random forest models,and the test set was used to evaluate the prediction performance of the model by comparing the sensitivity,specificity,accuracy,recall,precision,and area under the receiver operating characteristic curve.RESULTS Among the 210 patients with T2DM,74(35.34%)had DN.The validation dataset showed that the accuracies of the nomogram,decision tree,and random forest models in predicting DN in patients with T2DM were 0.746,0.714,and 0.730,respectively.The sensitivities were 0.710,0.710,and 0.806,respectively;the specificities were 0.844,0.875,and 0.844,respectively;the area under the receiver operating characteristic curve(AUC)of the patients were 0.811,0.735,and 0.850,respectively.The Delong test results revealed that the AUC values of the decision tree model were lower than those of the random forest and nomogram models(P<0.05),whereas the difference in AUC values of the random forest and column-line graph models was not statistically significant(P>0.05).CONCLUSION Among the three prediction models,random forest performs best and can help identify patients with T2DM at high risk of DN.