Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central com...Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.展开更多
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 rel...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.展开更多
Insulin resistance(IR)is widely recognized as a key contributor to metabolic disorders,and various surrogate indices have been developed to estimate IR in clinical and research settings.The hyperinsulinemic-euglycemic...Insulin resistance(IR)is widely recognized as a key contributor to metabolic disorders,and various surrogate indices have been developed to estimate IR in clinical and research settings.The hyperinsulinemic-euglycemic clamp is considered the gold standard method for assessing insulin resistance due to its precision;however,its complexity limits its widespread clinical application.Consequently,surrogate indices derived from fasting and post-load glucose and insulin levels have been developed to estimate IR,facilitating early detection and risk stratification in metabolic disorders.This mini-review discusses the clinical utility,strengths,and limitations of key IR indices,including the homeostasis model assessment of IR,quantitative insulin sensitivity check index,Matsuda index,and triglyceride-glucose index.Overall,the evidence presented to date suggests that these indices provide valuable estimates of IR in various popula-tions.Yet,their applicability varies depending on ethnic background,disease status,and clinical setting.Integrating these indices into routine clinical practice and research could improve metabolic risk assessment and guide preventive interventions.Further investigations are necessary to refine their accuracy and determine optimal cut-off values for various populations.展开更多
BACKGROUND Cardiovascular disease represents a major complication in patients with type 2 diabetes mellitus(T2DM),with insulin resistance(IR)recognized as a key underlying pathophysiological mechanism.The metabolic sc...BACKGROUND Cardiovascular disease represents a major complication in patients with type 2 diabetes mellitus(T2DM),with insulin resistance(IR)recognized as a key underlying pathophysiological mechanism.The metabolic score for IR(METS-IR),a simple,non-invasive,and insulin-independent surrogate marker of IR,has been validated for risk stratification and prognostic assessment in conditions such as hypertension,ischemic cardiomyopathy,and T2DM.Monitoring fluctuations in METS-IR levels among individuals with T2DM may facilitate early identification of elevated cardiovascular risk and inform timely therapeutic adjustments.AIM To investigate the association between METS-IR and cardiovascular risk in patients with T2DM and to evaluate its potential utility as a predictive biomarker.METHODS This study represents a secondary analysis of a multicenter randomized controlled trial,ultimately including 10191 patients with T2DM aged 40 years to 79 years,with a follow-up duration of approximately 10 years.Baseline METS-IR was calculated using triglycerides,body mass index,high-density lipoprotein cholesterol and fasting plasma glucose.The predictive value of METS-IR for major adverse cardiovascular events(MACEs),all-cause mortality,congestive heart failure,and major coronary heart disease events,was assessed using Cox proportional hazards models,restricted cubic spline analysis,and stratified subgroup analyses.Multivariable adjustments were performed to account for potential confounding factors.RESULTS The incidence of MACEs increased steadily across higher METS-IR quartiles.After adjusting for multiple confounding factors,hazard ratios comparing the highest to the lowest METS-IR quartile were 1.25[95%confidence interval(CI):1.08-1.45]for MACEs,1.55(95%CI:1.23-1.96)for cardiovascular death,1.39(95%CI:1.21-1.59)for allcause mortality,2.22(95%CI:1.74-2.82)for congestive heart failure,and 1.35(95%CI:1.17-1.56)for major coronary heart disease.Restricted cubic spline analysis supported a positive,dose-dependent relationship between rising METS-IR levels and cardiovascular risk.Moreover,adding METS-IR to conventional risk prediction models enhanced their performance,as evidenced by improvements in the C-statistic,net reclassification improvement,and integrated discrimination improvement.Subgroup analyses indicated possible interactions between METS-IR,hemoglobin A1c levels,and aspirin therapy.CONCLUSION METS-IR shows a strong correlation with cardiovascular risk in individuals with T2DM.Tracking METS-IR levels could enhance risk assessment and the prediction of cardiovascular events.展开更多
BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring except...BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is rare.CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of sepsis.Remarkably,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose level.CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically transient.Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.展开更多
OBJECTIVE To explore hypoglycemic effect of 95%ethanol fraction of Nitraria roborowskii Kom(NRK-C)and its possible mechanism evaluated in the type 2 diabetes mellitus(T2DM)mice.METHODS The body weight,organ indices,bl...OBJECTIVE To explore hypoglycemic effect of 95%ethanol fraction of Nitraria roborowskii Kom(NRK-C)and its possible mechanism evaluated in the type 2 diabetes mellitus(T2DM)mice.METHODS The body weight,organ indices,blood glucose levels,serum biochemical indexes,as well as HE/PAS histopathological section were all analyzed to assess the hypoglycemic effect of NRK-C in T2DM mice induced by a high-fat diet(HFD)combined with six intraperitoneal injections of 35 mg·kg^(-1)of streptozotocin(STZ).The Western blotting and immunofluorescence were further applied to determine the regulatory effect of NRK-C on key signaling proteins.RESULTS The fasting blood glucose levels were significantly reduced after 7 weeks of administration of NRK-C.In addition,NRK-C could also significantly improve glucose tolerance,hepatic glycogen levels,and lipid levels(total cholesterol,triglyceride,low density lipoprotein and high density lipoprotein),and significantly reduced insulin resistance of diabetic mice,which played an important role in the antidiabetic effects.Further mechanism research demonstrated that phosphorylated PI3K expression was up-regulated and p-GSK3βexpression was up-regulated after NRK-C intervention,indicating that NRK-C might exert a potential antidiabetic effect by modulating the PI3K/AKT signaling pathway.CONCLUSION All these results suggested that NRK-C might improve T2DM and had the potential to be used as an adjunctive therapy.展开更多
This editorial discusses the findings of Elbarky et al on the role of selenoprotein P1(SEPP1)in pediatric obesity and insulin resistance.Their study uncovered si-gnificantly lower SEPP1 Levels in children who were obe...This editorial discusses the findings of Elbarky et al on the role of selenoprotein P1(SEPP1)in pediatric obesity and insulin resistance.Their study uncovered si-gnificantly lower SEPP1 Levels in children who were obese compared with hea-lthy peers,demonstrating a negative correlation between SEPP1 levels and mea-sures of adiposity and insulin resistance.These findings suggest that SEPP1 is a biomarker useful in the early identification of insulin resistance in pediatric populations.This editorial emphasizes the clinical implications of the study and calls for further research to validate and explore the role of SEPP1 in metabolic health.展开更多
Recent studies have potentiated the essential role of androgens in normal follicu-logenesis and,therefore,female fertility.Contrastingly,excess androgen levels,i.e.,hyperandrogenism(HA),a hallmark characteristic of po...Recent studies have potentiated the essential role of androgens in normal follicu-logenesis and,therefore,female fertility.Contrastingly,excess androgen levels,i.e.,hyperandrogenism(HA),a hallmark characteristic of polycystic ovary syndrome,overrides the delicate balance of folliculogenesis,leading to follicular arrest and ovulatory issues.Insulin resistance(IR)has a profound effect on elevating androgen secretion and is considered one of the primary factors driving both ovarian androgen production and metabolic dysfunction in polycystic ovary syndrome.Together with IR,disruptions in key intraovarian and systemic factors,including activin,inhibin,follistatin,anti-Mullerian hormone,bone morpho-genetic proteins,growth differentiation factor-9 and Kit ligand,as well as dysreg-ulation in both the insulin and the transforming growth factor-βsuperfamily signaling pathway,contribute to follicular arrest,elevated androgen levels and metabolic dysfunction,exacerbating HA.Additionally,suppression of sex hormone-binding globulin,disrupted adipose-neuroendocrine signaling and altered microRNA expression heighten HA,with IR serving as the fundamental contributor.Emerging evidence implicates impaired atresia together with non-apoptotic cell death,such as ferroptosis and pyroptosis,which have also been associated with ovarian dysfunction.A comprehensive understanding of the most significant factors,particularly IR,which amplifies androgen production through hyperinsulinemia-mediated stimulation of theca cells,is essential for identifying targeted therapeutic strategies.展开更多
Objective This study aimed to investigate the association between insulin resistance and the risk of cardiovascular disease.Methods A cross-sectional study including 2128 participants aged 40-79 years was conducted us...Objective This study aimed to investigate the association between insulin resistance and the risk of cardiovascular disease.Methods A cross-sectional study including 2128 participants aged 40-79 years was conducted using data from the National Health and Nutrition Examination Survey from 1999 to 2018.The quantitative insulin sensitivity check index(QUICKI)and homeostasis model assessment ofβ-cell function(HOMA-β)were used as independent variables.The 10-year risk of a first hard atherosclerotic cardiovascular event was used as the dependent variable,with other potential confounding factors considered.Multivariate linear regression models and smooth curve fitting were used to assess the associations between insulin resistance and 10-year risk.Results A total of 2128 patients,comprising 1191 men and 937 women,were included in our analysis.The regression analyses revealed a negative correlation between the QUICKI score and the 10-year risk of a first hard atherosclerotic car-diovascular event[β=-8.85,CI(-15.77,-1.93)]after adjusting for age,race,body mass index,systolic blood pressure,diastolic blood pressure,hypertension treatment,smoking,diabetes,and low-density lipoprotein cholesterol.Conversely,an increase in HOMA-βwas associated with 10-year risk[β=6.84,CI(0.45,13.23)].Gender-specific subgroup analysis indicated that the QUICKI had aβvalue of 0.077(0.046,0.108)for men and 0.080(0.061,0.094)for women.Conclusion This study demonstrated that increased insulin resistance is linked to an increased risk of cardiovascular disease.展开更多
BACKGROUND Acute and extreme insulin resistance with persistent hyperglycemia requiring excessively high doses of insulin before rapidly resolving is rare and has been referred to as transient and extreme insulin resi...BACKGROUND Acute and extreme insulin resistance with persistent hyperglycemia requiring excessively high doses of insulin before rapidly resolving is rare and has been referred to as transient and extreme insulin resistance(TEIR).The underlying pathophysiology and optimal management of TEIR are poorly understood,and previous reports of TEIR in the literature are sparse.This report is the first description of TEIR in a patient requiring mechanical circulatory support(MCS).CASE SUMMARY A 62-year-old male developed cardiogenic shock and was placed on veno-arterial extracorporeal membrane oxygenation following percutaneous coronary intervention and successful revascularization.Over the next 24 hours,glucose levels rose and remained markedly elevated despite increasing insulin infusion rates and repeated boluses.The insulin infusion rate peaked at 450 units/hour,and the patient received 4300 units(33 units/kg)of insulin over the 24-hour period of peak insulin resistance.Insulin resistance resolved rapidly,necessitating an abrupt decrease in the insulin infusion rate and development of rebound hypoglycemia.CONCLUSION Onset of TEIR did not seem to correlate with end-organ hypoperfusion or vasoactive drug dosing.展开更多
Objective:To investigate whether nacre extract improves insulin sensitivity,brain glucose metabolism,and cognitive function in diabetic mice.Methods:Diabetic KK-Ay mice(n=5/group)were fed a standard diet or diets supp...Objective:To investigate whether nacre extract improves insulin sensitivity,brain glucose metabolism,and cognitive function in diabetic mice.Methods:Diabetic KK-Ay mice(n=5/group)were fed a standard diet or diets supplemented with nacre extract(125 or 250 mg/kg)for 13 weeks.Metabolic status was assessed by measuring fasting glucose and insulin levels,HOMA-IR,glucose tolerance,and insulin tolerance.The expression of IRS-1,IRS-2,and GLUT4 in the brain was analyzed by qPCR,Western blotting,and immunohistochemistry.Cognitive and anxiety-like behaviors were evaluated using the Y-maze,novel object recognition,Barnes maze,and open field tests.Results:Nacre extract significantly reduced fasting glucose and insulin levels,improved HOMA-IR,and enhanced glucose and insulin tolerance(P<0.05)in diabetic mice.It also restored GLUT4 expression and significantly upregulated SIRT1 and BDNF.Behavioral assessments showed significant improvements in memory and reduced anxiety-like behaviors.Conclusions:Nacre extract enhances insulin sensitivity,improves brain glucose metabolism,and alleviates cognitive and emotional dysfunction in diabetic mice.Further studies are warranted to verify the exact molecular mechanisms and efficacy of nacre extract in diabetes-associated metabolic and neurocognitive dysfunction.展开更多
Inflammation caused by obesity,particularly in adipose tissue and the liver,can lead to insulin resistance(IR)and trigger type 2 diabetes mellitus(T2DM).It is crucial to identify therapeutic agents that alleviate IR b...Inflammation caused by obesity,particularly in adipose tissue and the liver,can lead to insulin resistance(IR)and trigger type 2 diabetes mellitus(T2DM).It is crucial to identify therapeutic agents that alleviate IR by reducing inflammation.Here,we report that isobavachromene(IB),a flavonoid derived from Psoralea corylifolia Linn.,ameliorates IR in 3T3-L1 adipocytes by inhibiting the mitogen-activated protein kinase(MAPK)and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway.We first found that IB could promote glucose uptake in 3T3-L1 adipocytes by activating the phosphoinositide 3-kinase(PI-3K)/protein kinase B(Akt)signaling pathway and was more effective than the positive control sodium orthovanadate at concentrations ranging from 25 to 100μmol/L.Additionally,IB inhibited RAW264.7 macrophage infiltration into 3T3-L1 adipocytes and suppressed the secretion of inflammatory factors from RAW264.7 macrophages,as well as the phosphorylation levels of key proteins(NF-κB p65,extracellular-signal-regulated kinase 1/2(ERK1/2),Jun N-terminal kinase(JNK),and mitogen-activated protein kinase 38(p38))in the NF-κB and MAPK signaling pathways.In summary,IB improves glucose uptake in IR adipocytes,activates the PI-3K/Akt signaling pathway,inhibits the JNK and NF-κB inflammatory signaling pathways,and reduces adipocyte inflammation,thereby improving of IR in 3T3-L1 adipocytes.展开更多
It has been reported that sea cucumber intestine hydrolysates(SCIH)could promote glutamine metabolism in mice,while there is a close connection between glutamine metabolism and insulin sensitivity.However,the effect o...It has been reported that sea cucumber intestine hydrolysates(SCIH)could promote glutamine metabolism in mice,while there is a close connection between glutamine metabolism and insulin sensitivity.However,the effect of SCIH on insulin resistance is still unclear.The results showed that SCIH hydrolyzed by flavor protease had significant activity using the insulin-induced Hep G2 cell model.Animal experiments exhibited that SCIH supplementation significantly improved the high-fat and high-sucrose diet-induced impaired glucose tolerance,reduced fasting serum glucose and glycosylated serum protein.Besides,SCIH ameliorated islet vacuolization and decreased the pancreas TNF-αand IL-6 by 32.1%and 36.2%,respectively.Immunofluorescence staining results showed that SCIH promoted insulin secretion.Interestingly,SCIH significantly increased the liver glutamine levels and upregulated the expression of glutaminase1(GLS1)and glutamate dehydrogenase 1(GLUD1).Furthermore,SCIH increased liver acetyl-Co A levels to enhance histone acetylation and activate the gene transcription and translation on glucose metabolism-related IRS/PI3K/AKT signaling pathway,thereby attenuating insulin resistance.The present findings proposed the potential value for developing functional foods in SCIH utilization.展开更多
Type 2 diabetes mellitus (T2DM) and obesity are growing global pandemics thatshares the common characteristic of insulin resistance (IR). IR leads to progressive β-cell failure, worsening T2DM and its cardiovascular ...Type 2 diabetes mellitus (T2DM) and obesity are growing global pandemics thatshares the common characteristic of insulin resistance (IR). IR leads to progressive β-cell failure, worsening T2DM and its cardiovascular complications. Thus, earlydiagnosis of IR is important to prevent and reverse β-cell dedifferentiation.However, there is a lack of accessible, non-invasive and affordable tools to earlydiagnose and stratify IR. The gold standard method used in the research setting isthe hyperinsulinemic-euglycemic clamp, however it is invasive, laborious,expensive and difficult to apply at a large scale. Hou et al presents a potentialnovel surrogate biomarker for diagnosing IR in T2DM. Magnetic resonanceimaging derived biomarkers can potentially become the accessible and noninvasivealternative to the hyperinsulinemic-euglycemic clamp, enabling thetimely diagnosis of IR with potential clinical applications in T2DM treatments andpreventative care.展开更多
By searching the relevant literature in recent ten years,this paper summarizes the research progress of massage in the treatment of obesity-induced insulin resistance,in order to provide more basis for massage in the ...By searching the relevant literature in recent ten years,this paper summarizes the research progress of massage in the treatment of obesity-induced insulin resistance,in order to provide more basis for massage in the treatment of obesity-induced insulin resistance.展开更多
BACKGROUND Insulin resistance(IR)plays a critical role in the musculoskeletal metabolic disorders associated with type 2 diabetes mellitus(T2DM).AIM To develop multiparametric magnetic resonance imaging(MRI)-derived b...BACKGROUND Insulin resistance(IR)plays a critical role in the musculoskeletal metabolic disorders associated with type 2 diabetes mellitus(T2DM).AIM To develop multiparametric magnetic resonance imaging(MRI)-derived biomarkers and diagnostic models for non-invasive identification and stratification of IR.METHODS Parameters of paravertebral muscles and vertebra were evaluated using quantitative chemical shift-encoded MRI and diffusion tensor imaging protocols.Tripartite cohort analyses were conducted through Kruskal-Wallis H tests with post hoc Dunn-Bonferroni correction for MRI-derived metrics.Diagnostic performance for T2DM-IR was assessed after selecting the most significant features through Z-score standardization and multinomial logistic regression models.RESULTS This study evaluated 97 subjects(control:39 subjects,T2DM-IR:18 subjects,T2DM patients without IR:40 subjects)using multiparametric MRI protocols.Significant intergroup differences were observed in the cross-sectional area(P=0.047)and apparent diffusion coefficient(P=0.027)of the psoas,and the crosssectional area(P=0.042)of the erector.More intramyocellular lipid(IMCL)in the psoas(P=0.001)and erector(P=0.004)were found in the T2DM-IR group.Multinomial receiver operating characteristic curve analysis demonstrated that IMCL of the erector performed better(area under the curve=0.838,sensitivity:0.800,specificity:0.938)in the diagnosis of T2DM-IR.CONCLUSION IMCL in erector emerges as a highly discriminative metric for T2DM-IR diagnosis.Multiparametric MRI enables non-invasive quantification of early musculoskeletal metabolic injury,providing reliable biomarkers for IR identification and stratification.展开更多
Insulin plays a crucial role in the metabolic priming and proliferation of neural stem cells(NSCs).However,insulin resistance(IR)is associated with impaired NSC proliferation and cognitive dysfunction,which are the ha...Insulin plays a crucial role in the metabolic priming and proliferation of neural stem cells(NSCs).However,insulin resistance(IR)is associated with impaired NSC proliferation and cognitive dysfunction,which are the hallmarks of psychiatric disorders(PDs).In addition to insulin,de novo lipogenesis(DNL)also plays an essential role in NSC proliferation and function as it supplies fatty acids for membrane phospholipid synthesis and cell signaling.However,enhanced DNL is associated with lipid/fatty acid accumulation,IR,and impaired NSC proliferation.Intriguingly,data from lipidomic studies suggest that DNL could be enhanced before the onset of classical symptoms in patients with PDs.Further,evidence suggests that patients with PDs may develop IR during childhood or before adolescence;therefore,DNL could be enhanced preceding the development of IR.Regarding treatment,while most antidepressants and antipsychotic drugs have been shown to further deteriorate IR and stimulate DNL,various adjunctive drugs/therapies,including chemical,physical,and stem cell therapy,which have shown promising success in treating PDs,reduce DNL while enhancing insulin sensitivity,NSC proliferation,and cognitive function in laboratory animals.Preliminary clinical outcomes and future prospects of these adjunctive drugs/therapies,especially stem cell therapy in treating PDs including schizophrenia and depression,are discussed.展开更多
Insulin resistance is a key pathological process in the development of type 2 diabetes,which can also lead to depression,anxiety and other symptoms.With the accelerated pace of life,food with high-energy and additives...Insulin resistance is a key pathological process in the development of type 2 diabetes,which can also lead to depression,anxiety and other symptoms.With the accelerated pace of life,food with high-energy and additives is becoming more and more common in people's diet.Propionate is a naturally existing short-chain fatty acid salt widely used as a food preservative,but studies have found that low concentrations of propionate can induce insulin resistance.Theaflavins(TFs)are characteristic components of black tea,which have hypoglycemic and lipid-lowering effects.In the present study,propionate combined with high-fat diet was used to induce insulin resistance in mice and treated them with TFs.The results showed that propionate could aggravate insulin resistance and anxiety induced by high-fat diet in mice.TFs alleviated insulin resistance and anxiety induced by propionate combined with high-fat diet by improving the disorder of metabolic gene expression and inflammation in the adipose and liver tissue,as well as neuroinflammation in the brain.Our study suggests that the food additive propionate combined with a high-fat diet may be harmful to organismal health.As a natural drug,TFs have the potential to alleviate insulin resistance induced by propionate combined with high-fat diet.展开更多
BACKGROUND Sodium-glucose cotransporter 2(SGLT2)inhibitors are widely used for the tr-eatment of type 2 diabetes(T2D).AIM To evaluate the influence of SGLT2 inhibitors on homeostasis model assessment of insulin resist...BACKGROUND Sodium-glucose cotransporter 2(SGLT2)inhibitors are widely used for the tr-eatment of type 2 diabetes(T2D).AIM To evaluate the influence of SGLT2 inhibitors on homeostasis model assessment of insulin resistance(HOMA-IR)andβ-cell function(HOMA-β)in patients with T2D in a meta-analysis.METHODS Randomized controlled trials(RCTs)comparing SGLT2 inhibitors to placebo in T2D patients,with a minimum treatment duration of 12 weeks,were searched using the PubMed,EMBASE,and Cochrane Library databases.Risk of bias was assessed using the Cochrane Risk of Bias Tool,and the certainty of evidence was evaluated using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)system.Changes in HOMA-IR and HOMA-βwere the outcomes analyzed.Meta-analyses were performed using a random-effects model by incorporating the potential influences of heterogeneity.RESULTS Of 1388 articles identified,24 RCTs met the inclusion criteria.23 of the included studies were double-blind RCTs with low risk of bias.Pooled results including 2272 patients showed that SGLT2 inhibitors significantly reduced HOMA-IR compared to placebo[mean difference(MD)=-0.81,95%confidence interval(CI):-1.11 to-0.52,P<0.001;I2=82%],indicating reduced insulin resistance.Addi-tionally,meta-analysis with 2845 patients suggested that SGLT2 inhibitors significantly increased HOMA-β(MD=7.90,95%CI:5.44-10.37,P<0.001;I2=74%)compared to placebo in patients with T2D,indicating improvedβ-cell function.Based on GRADE assessment,the certainty of evidence was rated moderate for both outcomes due to heterogeneity.Subgroup analyses showed that HOMA-βincreased more substantially in non-Asian studies than in Asian studies(P for subgroup difference<0.01).Subgroup analyses according to the individual medications of SGLT2 inhibitors all showed significant improvement of HOMA-IR and HOMA-β(P all<0.05).No significant publication bias was detected(P for Egger’s test all>0.05).CONCLUSION SGLT2 inhibitors are associated with improvements in insulin resistance andβ-cell function in patients with T2D,although the certainty of evidence is moderate due to heterogeneity.展开更多
BACKGROUND Some non-insulin-based insulin resistance(IR)indices have been found to be associated with metabolic syndrome(MetS);however,few cohort studies have compared the capacities of these indices for predicting in...BACKGROUND Some non-insulin-based insulin resistance(IR)indices have been found to be associated with metabolic syndrome(MetS);however,few cohort studies have compared the capacities of these indices for predicting incident MetS in young adults.AIM To investigate the associations of various non-insulin-based IR(NI-IR)indices with new-onset MetS in young military personnel.METHODS A total of 2890 armed forces personnel in Taiwan who were aged 18-39 years and did not have MetS at baseline were followed to monitor the incidence of new-onset MetS from 2014 to the end of 2020.Six NI-IR indices,including the metabolic score for IR(METS-IR),triglyceride(TG)-to-high-density lipoprotein cholesterol(HDL-C)ratio,TG glucose(TyG)index,Zhejiang University(ZJU)index,total cholesterol(TC)-to-HDL-C ratio,and alanine transaminase(ALT)-to-aspartate transaminase(AST)ratio,were defined according to specific criteria.Incident MetS was identified on the basis of each annual health examination using the International Diabetes Federation criteria.Multiple Cox regression analyses were conducted,adjusting for age,sex,waist circumference,smoking status,alcohol consumption status,and physical activity,to assess the associations of the NI-IR indices with incident MetS.The area under the receiver operating characteristic curve(AUROC)was used to compare the capacities of these NI-IR indices for predicting new-onset MetS.RESULTS During a median follow-up of 5.8 years,there were 673 patients with new-onset MetS(23%).All six of the NI-IR indices were significantly and positively associated with incident MetS.In the entire cohort,the greatest AUROC was found for the METS-IR[0.782;95%confidence interval(CI):0.762-0.801;all P values compared to the other NIIR indices<0.05],followed by the TG/HDL-C ratio(0.752;95%CI:0.731-0.772),ZJU index(0.743;95%CI:0.722-0.764),TyG index(0.734;95%CI:0.713-0.756),TC/HDL-C ratio(0.731;95%CI:0.709-0.752),and then the ALT/AST ratio(0.734;95%CI:0.713-0.756).CONCLUSION This study suggests that almost all the NI-IR indices are associated with the development of MetS in military young adults.The METS-IR is the strongest predictor of new-onset MetS before midlife.展开更多
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC)+6 种基金STI2030-Major Projects(2021ZD0202700,to HY)the National Natural Science Foundation of China(32241004,to HY)the Natural Science Foundation of Zhejiang Province of China(LR24C090001,to HY)Key R&D Program of Zhejiang Province(2024SSYS0017,to HY)CAMS Innovation Fund for Medical Sciences(2019-12M-5-057,to HY)Fundamental Research Funds for the Central Universities(226-2022-00193,to HY)the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT310-01,to HY)。
文摘Type 2 diabetes mellitus has central complications:Diabetes,a metabolic disorder primarily characterized by hyperglycemia due to insufficient insulin secretion,or impaired insulin signaling,has significant central complications.Type 2 diabetes mellitus(T2DM),the most prevalent type of diabetes,affects more than 38 million individuals in the United States(approximately 1 in 10)and is defined by chronic hyperglycemia and insulin resistance,which refers to a reduced cellular response to insulin.
基金support from Region Stockholm,ALF-project(FoUI-960041)Open Access funding is provided by Karolinska Institute(both to IM)。
文摘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.
文摘Insulin resistance(IR)is widely recognized as a key contributor to metabolic disorders,and various surrogate indices have been developed to estimate IR in clinical and research settings.The hyperinsulinemic-euglycemic clamp is considered the gold standard method for assessing insulin resistance due to its precision;however,its complexity limits its widespread clinical application.Consequently,surrogate indices derived from fasting and post-load glucose and insulin levels have been developed to estimate IR,facilitating early detection and risk stratification in metabolic disorders.This mini-review discusses the clinical utility,strengths,and limitations of key IR indices,including the homeostasis model assessment of IR,quantitative insulin sensitivity check index,Matsuda index,and triglyceride-glucose index.Overall,the evidence presented to date suggests that these indices provide valuable estimates of IR in various popula-tions.Yet,their applicability varies depending on ethnic background,disease status,and clinical setting.Integrating these indices into routine clinical practice and research could improve metabolic risk assessment and guide preventive interventions.Further investigations are necessary to refine their accuracy and determine optimal cut-off values for various populations.
基金Supported by the Key Research and Development Plan of Hunan Province,No.2022SK2013Central South University,No.2024ZZTS0931.
文摘BACKGROUND Cardiovascular disease represents a major complication in patients with type 2 diabetes mellitus(T2DM),with insulin resistance(IR)recognized as a key underlying pathophysiological mechanism.The metabolic score for IR(METS-IR),a simple,non-invasive,and insulin-independent surrogate marker of IR,has been validated for risk stratification and prognostic assessment in conditions such as hypertension,ischemic cardiomyopathy,and T2DM.Monitoring fluctuations in METS-IR levels among individuals with T2DM may facilitate early identification of elevated cardiovascular risk and inform timely therapeutic adjustments.AIM To investigate the association between METS-IR and cardiovascular risk in patients with T2DM and to evaluate its potential utility as a predictive biomarker.METHODS This study represents a secondary analysis of a multicenter randomized controlled trial,ultimately including 10191 patients with T2DM aged 40 years to 79 years,with a follow-up duration of approximately 10 years.Baseline METS-IR was calculated using triglycerides,body mass index,high-density lipoprotein cholesterol and fasting plasma glucose.The predictive value of METS-IR for major adverse cardiovascular events(MACEs),all-cause mortality,congestive heart failure,and major coronary heart disease events,was assessed using Cox proportional hazards models,restricted cubic spline analysis,and stratified subgroup analyses.Multivariable adjustments were performed to account for potential confounding factors.RESULTS The incidence of MACEs increased steadily across higher METS-IR quartiles.After adjusting for multiple confounding factors,hazard ratios comparing the highest to the lowest METS-IR quartile were 1.25[95%confidence interval(CI):1.08-1.45]for MACEs,1.55(95%CI:1.23-1.96)for cardiovascular death,1.39(95%CI:1.21-1.59)for allcause mortality,2.22(95%CI:1.74-2.82)for congestive heart failure,and 1.35(95%CI:1.17-1.56)for major coronary heart disease.Restricted cubic spline analysis supported a positive,dose-dependent relationship between rising METS-IR levels and cardiovascular risk.Moreover,adding METS-IR to conventional risk prediction models enhanced their performance,as evidenced by improvements in the C-statistic,net reclassification improvement,and integrated discrimination improvement.Subgroup analyses indicated possible interactions between METS-IR,hemoglobin A1c levels,and aspirin therapy.CONCLUSION METS-IR shows a strong correlation with cardiovascular risk in individuals with T2DM.Tracking METS-IR levels could enhance risk assessment and the prediction of cardiovascular events.
文摘BACKGROUND Acute hyperglycemia due to insulin resistance is common in critically ill patients,typically managed with insulin infusion.However,the occurrence of transient extreme insulin resistance(EIR)requiring exceptional high-dose insulin is rare.CASE SUMMARY We present the case of a 68-year-old woman with pneumonia who suffered an out-of-hospital cardiac arrest,subsequently developing transient EIR following a new episode of sepsis.Remarkably,insulin resistance rapidly reversed when the insulin infusion rate peaked at 960 units/hour(a total of 18224 units on that day),and it was promptly titrated down to zero upon achieving the target glucose level.CONCLUSION Exceptional high-dose insulin infusion may be required in critically ill patients with stress-related EIR,which is typically transient.Clinicians should be aware of the phenomenon and cautious to avoid hypoglycemia and fluid overload during the steep titration of high-dose insulin infusion.
文摘OBJECTIVE To explore hypoglycemic effect of 95%ethanol fraction of Nitraria roborowskii Kom(NRK-C)and its possible mechanism evaluated in the type 2 diabetes mellitus(T2DM)mice.METHODS The body weight,organ indices,blood glucose levels,serum biochemical indexes,as well as HE/PAS histopathological section were all analyzed to assess the hypoglycemic effect of NRK-C in T2DM mice induced by a high-fat diet(HFD)combined with six intraperitoneal injections of 35 mg·kg^(-1)of streptozotocin(STZ).The Western blotting and immunofluorescence were further applied to determine the regulatory effect of NRK-C on key signaling proteins.RESULTS The fasting blood glucose levels were significantly reduced after 7 weeks of administration of NRK-C.In addition,NRK-C could also significantly improve glucose tolerance,hepatic glycogen levels,and lipid levels(total cholesterol,triglyceride,low density lipoprotein and high density lipoprotein),and significantly reduced insulin resistance of diabetic mice,which played an important role in the antidiabetic effects.Further mechanism research demonstrated that phosphorylated PI3K expression was up-regulated and p-GSK3βexpression was up-regulated after NRK-C intervention,indicating that NRK-C might exert a potential antidiabetic effect by modulating the PI3K/AKT signaling pathway.CONCLUSION All these results suggested that NRK-C might improve T2DM and had the potential to be used as an adjunctive therapy.
文摘This editorial discusses the findings of Elbarky et al on the role of selenoprotein P1(SEPP1)in pediatric obesity and insulin resistance.Their study uncovered si-gnificantly lower SEPP1 Levels in children who were obese compared with hea-lthy peers,demonstrating a negative correlation between SEPP1 levels and mea-sures of adiposity and insulin resistance.These findings suggest that SEPP1 is a biomarker useful in the early identification of insulin resistance in pediatric populations.This editorial emphasizes the clinical implications of the study and calls for further research to validate and explore the role of SEPP1 in metabolic health.
基金Supported by Incentive Funding for Rated Researchers from the National Research Foundation,Pretoria,No.145943Research Reward from the Research Office of the University of KwaZulu-Natal,Durban,South Africa.
文摘Recent studies have potentiated the essential role of androgens in normal follicu-logenesis and,therefore,female fertility.Contrastingly,excess androgen levels,i.e.,hyperandrogenism(HA),a hallmark characteristic of polycystic ovary syndrome,overrides the delicate balance of folliculogenesis,leading to follicular arrest and ovulatory issues.Insulin resistance(IR)has a profound effect on elevating androgen secretion and is considered one of the primary factors driving both ovarian androgen production and metabolic dysfunction in polycystic ovary syndrome.Together with IR,disruptions in key intraovarian and systemic factors,including activin,inhibin,follistatin,anti-Mullerian hormone,bone morpho-genetic proteins,growth differentiation factor-9 and Kit ligand,as well as dysreg-ulation in both the insulin and the transforming growth factor-βsuperfamily signaling pathway,contribute to follicular arrest,elevated androgen levels and metabolic dysfunction,exacerbating HA.Additionally,suppression of sex hormone-binding globulin,disrupted adipose-neuroendocrine signaling and altered microRNA expression heighten HA,with IR serving as the fundamental contributor.Emerging evidence implicates impaired atresia together with non-apoptotic cell death,such as ferroptosis and pyroptosis,which have also been associated with ovarian dysfunction.A comprehensive understanding of the most significant factors,particularly IR,which amplifies androgen production through hyperinsulinemia-mediated stimulation of theca cells,is essential for identifying targeted therapeutic strategies.
基金supported by Hostital Capability Enhancement Project of Xiyuan Hospital,CACMS.(No.XYZX0405-25).
文摘Objective This study aimed to investigate the association between insulin resistance and the risk of cardiovascular disease.Methods A cross-sectional study including 2128 participants aged 40-79 years was conducted using data from the National Health and Nutrition Examination Survey from 1999 to 2018.The quantitative insulin sensitivity check index(QUICKI)and homeostasis model assessment ofβ-cell function(HOMA-β)were used as independent variables.The 10-year risk of a first hard atherosclerotic cardiovascular event was used as the dependent variable,with other potential confounding factors considered.Multivariate linear regression models and smooth curve fitting were used to assess the associations between insulin resistance and 10-year risk.Results A total of 2128 patients,comprising 1191 men and 937 women,were included in our analysis.The regression analyses revealed a negative correlation between the QUICKI score and the 10-year risk of a first hard atherosclerotic car-diovascular event[β=-8.85,CI(-15.77,-1.93)]after adjusting for age,race,body mass index,systolic blood pressure,diastolic blood pressure,hypertension treatment,smoking,diabetes,and low-density lipoprotein cholesterol.Conversely,an increase in HOMA-βwas associated with 10-year risk[β=6.84,CI(0.45,13.23)].Gender-specific subgroup analysis indicated that the QUICKI had aβvalue of 0.077(0.046,0.108)for men and 0.080(0.061,0.094)for women.Conclusion This study demonstrated that increased insulin resistance is linked to an increased risk of cardiovascular disease.
文摘BACKGROUND Acute and extreme insulin resistance with persistent hyperglycemia requiring excessively high doses of insulin before rapidly resolving is rare and has been referred to as transient and extreme insulin resistance(TEIR).The underlying pathophysiology and optimal management of TEIR are poorly understood,and previous reports of TEIR in the literature are sparse.This report is the first description of TEIR in a patient requiring mechanical circulatory support(MCS).CASE SUMMARY A 62-year-old male developed cardiogenic shock and was placed on veno-arterial extracorporeal membrane oxygenation following percutaneous coronary intervention and successful revascularization.Over the next 24 hours,glucose levels rose and remained markedly elevated despite increasing insulin infusion rates and repeated boluses.The insulin infusion rate peaked at 450 units/hour,and the patient received 4300 units(33 units/kg)of insulin over the 24-hour period of peak insulin resistance.Insulin resistance resolved rapidly,necessitating an abrupt decrease in the insulin infusion rate and development of rebound hypoglycemia.CONCLUSION Onset of TEIR did not seem to correlate with end-organ hypoperfusion or vasoactive drug dosing.
文摘Objective:To investigate whether nacre extract improves insulin sensitivity,brain glucose metabolism,and cognitive function in diabetic mice.Methods:Diabetic KK-Ay mice(n=5/group)were fed a standard diet or diets supplemented with nacre extract(125 or 250 mg/kg)for 13 weeks.Metabolic status was assessed by measuring fasting glucose and insulin levels,HOMA-IR,glucose tolerance,and insulin tolerance.The expression of IRS-1,IRS-2,and GLUT4 in the brain was analyzed by qPCR,Western blotting,and immunohistochemistry.Cognitive and anxiety-like behaviors were evaluated using the Y-maze,novel object recognition,Barnes maze,and open field tests.Results:Nacre extract significantly reduced fasting glucose and insulin levels,improved HOMA-IR,and enhanced glucose and insulin tolerance(P<0.05)in diabetic mice.It also restored GLUT4 expression and significantly upregulated SIRT1 and BDNF.Behavioral assessments showed significant improvements in memory and reduced anxiety-like behaviors.Conclusions:Nacre extract enhances insulin sensitivity,improves brain glucose metabolism,and alleviates cognitive and emotional dysfunction in diabetic mice.Further studies are warranted to verify the exact molecular mechanisms and efficacy of nacre extract in diabetes-associated metabolic and neurocognitive dysfunction.
基金supported by National Key R&D Program of China(2022YFF1100300)the Central Guidance on Local Science and Technology Development Found of Shenzhen,China(2021Szvup030).
文摘Inflammation caused by obesity,particularly in adipose tissue and the liver,can lead to insulin resistance(IR)and trigger type 2 diabetes mellitus(T2DM).It is crucial to identify therapeutic agents that alleviate IR by reducing inflammation.Here,we report that isobavachromene(IB),a flavonoid derived from Psoralea corylifolia Linn.,ameliorates IR in 3T3-L1 adipocytes by inhibiting the mitogen-activated protein kinase(MAPK)and nuclear factor kappa-light-chain-enhancer of activated B cells(NF-κB)signaling pathway.We first found that IB could promote glucose uptake in 3T3-L1 adipocytes by activating the phosphoinositide 3-kinase(PI-3K)/protein kinase B(Akt)signaling pathway and was more effective than the positive control sodium orthovanadate at concentrations ranging from 25 to 100μmol/L.Additionally,IB inhibited RAW264.7 macrophage infiltration into 3T3-L1 adipocytes and suppressed the secretion of inflammatory factors from RAW264.7 macrophages,as well as the phosphorylation levels of key proteins(NF-κB p65,extracellular-signal-regulated kinase 1/2(ERK1/2),Jun N-terminal kinase(JNK),and mitogen-activated protein kinase 38(p38))in the NF-κB and MAPK signaling pathways.In summary,IB improves glucose uptake in IR adipocytes,activates the PI-3K/Akt signaling pathway,inhibits the JNK and NF-κB inflammatory signaling pathways,and reduces adipocyte inflammation,thereby improving of IR in 3T3-L1 adipocytes.
基金supported by National Key Research and Development Program of China(2023YFF1103901)the Taishan Scholars Program(tstp20240812)+2 种基金China Postdoctoral Science Foundation(2024M763107)Postdoctoral Fellowship Program of CPSF(GZC20241617)Youth Innovation Team Program of Universities in Shandong Province(2023KJ040)。
文摘It has been reported that sea cucumber intestine hydrolysates(SCIH)could promote glutamine metabolism in mice,while there is a close connection between glutamine metabolism and insulin sensitivity.However,the effect of SCIH on insulin resistance is still unclear.The results showed that SCIH hydrolyzed by flavor protease had significant activity using the insulin-induced Hep G2 cell model.Animal experiments exhibited that SCIH supplementation significantly improved the high-fat and high-sucrose diet-induced impaired glucose tolerance,reduced fasting serum glucose and glycosylated serum protein.Besides,SCIH ameliorated islet vacuolization and decreased the pancreas TNF-αand IL-6 by 32.1%and 36.2%,respectively.Immunofluorescence staining results showed that SCIH promoted insulin secretion.Interestingly,SCIH significantly increased the liver glutamine levels and upregulated the expression of glutaminase1(GLS1)and glutamate dehydrogenase 1(GLUD1).Furthermore,SCIH increased liver acetyl-Co A levels to enhance histone acetylation and activate the gene transcription and translation on glucose metabolism-related IRS/PI3K/AKT signaling pathway,thereby attenuating insulin resistance.The present findings proposed the potential value for developing functional foods in SCIH utilization.
文摘Type 2 diabetes mellitus (T2DM) and obesity are growing global pandemics thatshares the common characteristic of insulin resistance (IR). IR leads to progressive β-cell failure, worsening T2DM and its cardiovascular complications. Thus, earlydiagnosis of IR is important to prevent and reverse β-cell dedifferentiation.However, there is a lack of accessible, non-invasive and affordable tools to earlydiagnose and stratify IR. The gold standard method used in the research setting isthe hyperinsulinemic-euglycemic clamp, however it is invasive, laborious,expensive and difficult to apply at a large scale. Hou et al presents a potentialnovel surrogate biomarker for diagnosing IR in T2DM. Magnetic resonanceimaging derived biomarkers can potentially become the accessible and noninvasivealternative to the hyperinsulinemic-euglycemic clamp, enabling thetimely diagnosis of IR with potential clinical applications in T2DM treatments andpreventative care.
基金Supported by National Natural Science Foundation of China (82174525)Natural Science Foundation of Jilin Province (YDZJ202301ZYTS469)+2 种基金Science and Technology Research Project of Jilin Provincial Department of Education in 2022 (JJKH20230966KJ)Youth Excellent Discipline Backbone Training Program of Changchun University of Chinese Medicine (202304)2023 College Student Innovation and Entrepreneurship Training Project in Jilin Province (S202310199043).
文摘By searching the relevant literature in recent ten years,this paper summarizes the research progress of massage in the treatment of obesity-induced insulin resistance,in order to provide more basis for massage in the treatment of obesity-induced insulin resistance.
基金Supported by National Natural Science Foundation of China,No.81930045 and No.31630025.
文摘BACKGROUND Insulin resistance(IR)plays a critical role in the musculoskeletal metabolic disorders associated with type 2 diabetes mellitus(T2DM).AIM To develop multiparametric magnetic resonance imaging(MRI)-derived biomarkers and diagnostic models for non-invasive identification and stratification of IR.METHODS Parameters of paravertebral muscles and vertebra were evaluated using quantitative chemical shift-encoded MRI and diffusion tensor imaging protocols.Tripartite cohort analyses were conducted through Kruskal-Wallis H tests with post hoc Dunn-Bonferroni correction for MRI-derived metrics.Diagnostic performance for T2DM-IR was assessed after selecting the most significant features through Z-score standardization and multinomial logistic regression models.RESULTS This study evaluated 97 subjects(control:39 subjects,T2DM-IR:18 subjects,T2DM patients without IR:40 subjects)using multiparametric MRI protocols.Significant intergroup differences were observed in the cross-sectional area(P=0.047)and apparent diffusion coefficient(P=0.027)of the psoas,and the crosssectional area(P=0.042)of the erector.More intramyocellular lipid(IMCL)in the psoas(P=0.001)and erector(P=0.004)were found in the T2DM-IR group.Multinomial receiver operating characteristic curve analysis demonstrated that IMCL of the erector performed better(area under the curve=0.838,sensitivity:0.800,specificity:0.938)in the diagnosis of T2DM-IR.CONCLUSION IMCL in erector emerges as a highly discriminative metric for T2DM-IR diagnosis.Multiparametric MRI enables non-invasive quantification of early musculoskeletal metabolic injury,providing reliable biomarkers for IR identification and stratification.
文摘Insulin plays a crucial role in the metabolic priming and proliferation of neural stem cells(NSCs).However,insulin resistance(IR)is associated with impaired NSC proliferation and cognitive dysfunction,which are the hallmarks of psychiatric disorders(PDs).In addition to insulin,de novo lipogenesis(DNL)also plays an essential role in NSC proliferation and function as it supplies fatty acids for membrane phospholipid synthesis and cell signaling.However,enhanced DNL is associated with lipid/fatty acid accumulation,IR,and impaired NSC proliferation.Intriguingly,data from lipidomic studies suggest that DNL could be enhanced before the onset of classical symptoms in patients with PDs.Further,evidence suggests that patients with PDs may develop IR during childhood or before adolescence;therefore,DNL could be enhanced preceding the development of IR.Regarding treatment,while most antidepressants and antipsychotic drugs have been shown to further deteriorate IR and stimulate DNL,various adjunctive drugs/therapies,including chemical,physical,and stem cell therapy,which have shown promising success in treating PDs,reduce DNL while enhancing insulin sensitivity,NSC proliferation,and cognitive function in laboratory animals.Preliminary clinical outcomes and future prospects of these adjunctive drugs/therapies,especially stem cell therapy in treating PDs including schizophrenia and depression,are discussed.
基金jointly supported by Special Fund for Basic Research on Scientific Instruments of the Chinese National Natural Science Foundation(62027812)National Innovation and Entrepreneurship Project for College Students(202210055092)。
文摘Insulin resistance is a key pathological process in the development of type 2 diabetes,which can also lead to depression,anxiety and other symptoms.With the accelerated pace of life,food with high-energy and additives is becoming more and more common in people's diet.Propionate is a naturally existing short-chain fatty acid salt widely used as a food preservative,but studies have found that low concentrations of propionate can induce insulin resistance.Theaflavins(TFs)are characteristic components of black tea,which have hypoglycemic and lipid-lowering effects.In the present study,propionate combined with high-fat diet was used to induce insulin resistance in mice and treated them with TFs.The results showed that propionate could aggravate insulin resistance and anxiety induced by high-fat diet in mice.TFs alleviated insulin resistance and anxiety induced by propionate combined with high-fat diet by improving the disorder of metabolic gene expression and inflammation in the adipose and liver tissue,as well as neuroinflammation in the brain.Our study suggests that the food additive propionate combined with a high-fat diet may be harmful to organismal health.As a natural drug,TFs have the potential to alleviate insulin resistance induced by propionate combined with high-fat diet.
文摘BACKGROUND Sodium-glucose cotransporter 2(SGLT2)inhibitors are widely used for the tr-eatment of type 2 diabetes(T2D).AIM To evaluate the influence of SGLT2 inhibitors on homeostasis model assessment of insulin resistance(HOMA-IR)andβ-cell function(HOMA-β)in patients with T2D in a meta-analysis.METHODS Randomized controlled trials(RCTs)comparing SGLT2 inhibitors to placebo in T2D patients,with a minimum treatment duration of 12 weeks,were searched using the PubMed,EMBASE,and Cochrane Library databases.Risk of bias was assessed using the Cochrane Risk of Bias Tool,and the certainty of evidence was evaluated using the Grading of Recommendations,Assessment,Development and Evaluation(GRADE)system.Changes in HOMA-IR and HOMA-βwere the outcomes analyzed.Meta-analyses were performed using a random-effects model by incorporating the potential influences of heterogeneity.RESULTS Of 1388 articles identified,24 RCTs met the inclusion criteria.23 of the included studies were double-blind RCTs with low risk of bias.Pooled results including 2272 patients showed that SGLT2 inhibitors significantly reduced HOMA-IR compared to placebo[mean difference(MD)=-0.81,95%confidence interval(CI):-1.11 to-0.52,P<0.001;I2=82%],indicating reduced insulin resistance.Addi-tionally,meta-analysis with 2845 patients suggested that SGLT2 inhibitors significantly increased HOMA-β(MD=7.90,95%CI:5.44-10.37,P<0.001;I2=74%)compared to placebo in patients with T2D,indicating improvedβ-cell function.Based on GRADE assessment,the certainty of evidence was rated moderate for both outcomes due to heterogeneity.Subgroup analyses showed that HOMA-βincreased more substantially in non-Asian studies than in Asian studies(P for subgroup difference<0.01).Subgroup analyses according to the individual medications of SGLT2 inhibitors all showed significant improvement of HOMA-IR and HOMA-β(P all<0.05).No significant publication bias was detected(P for Egger’s test all>0.05).CONCLUSION SGLT2 inhibitors are associated with improvements in insulin resistance andβ-cell function in patients with T2D,although the certainty of evidence is moderate due to heterogeneity.
基金Supported by Medical Affairs Bureau Ministry of National Defense,No.MND-MAB-D-114222Hualien Armed Forces General Hospital,No.HAFGH-D-114008.
文摘BACKGROUND Some non-insulin-based insulin resistance(IR)indices have been found to be associated with metabolic syndrome(MetS);however,few cohort studies have compared the capacities of these indices for predicting incident MetS in young adults.AIM To investigate the associations of various non-insulin-based IR(NI-IR)indices with new-onset MetS in young military personnel.METHODS A total of 2890 armed forces personnel in Taiwan who were aged 18-39 years and did not have MetS at baseline were followed to monitor the incidence of new-onset MetS from 2014 to the end of 2020.Six NI-IR indices,including the metabolic score for IR(METS-IR),triglyceride(TG)-to-high-density lipoprotein cholesterol(HDL-C)ratio,TG glucose(TyG)index,Zhejiang University(ZJU)index,total cholesterol(TC)-to-HDL-C ratio,and alanine transaminase(ALT)-to-aspartate transaminase(AST)ratio,were defined according to specific criteria.Incident MetS was identified on the basis of each annual health examination using the International Diabetes Federation criteria.Multiple Cox regression analyses were conducted,adjusting for age,sex,waist circumference,smoking status,alcohol consumption status,and physical activity,to assess the associations of the NI-IR indices with incident MetS.The area under the receiver operating characteristic curve(AUROC)was used to compare the capacities of these NI-IR indices for predicting new-onset MetS.RESULTS During a median follow-up of 5.8 years,there were 673 patients with new-onset MetS(23%).All six of the NI-IR indices were significantly and positively associated with incident MetS.In the entire cohort,the greatest AUROC was found for the METS-IR[0.782;95%confidence interval(CI):0.762-0.801;all P values compared to the other NIIR indices<0.05],followed by the TG/HDL-C ratio(0.752;95%CI:0.731-0.772),ZJU index(0.743;95%CI:0.722-0.764),TyG index(0.734;95%CI:0.713-0.756),TC/HDL-C ratio(0.731;95%CI:0.709-0.752),and then the ALT/AST ratio(0.734;95%CI:0.713-0.756).CONCLUSION This study suggests that almost all the NI-IR indices are associated with the development of MetS in military young adults.The METS-IR is the strongest predictor of new-onset MetS before midlife.
