Development of diabetic complications and influencing factors among 32653 type 2 diabetes patients:retrospective cohort study using a multi-state Markov

Background:Patients with type 2 diabetes are at high risk for developing multiple chronic complications.However,there is a lack of studies of the cumulative number of diabetic complications in China.Methods:A retrospective cohort study was performed from 2009 to 2021.Type 2 diabetes patients who were first diagnosed after the age of 35 years between January 1,2009,and December 31,2017,were included.Five states were defined according to the number of chronic complications:no(S0),one(S1),two(S2),three(S3),and four or more complications(S4).A multi-state Markov model was constructed to estimate transition probability,transition intensity,mean sojourn time,and the possible factors for each state.Results:The study included 32653 type 2 diabetes patients(mean age,59.59 years;15929(48.8%)male),and mean follow-up time of 7.75 years.In all,4375 transitions were observed.The 12-year transition probability of from state S0 to S1 was the lowest at 16.4%,while that from S2 to S3 was the highest,at 45.6%.Higher fasting blood glucose,lower high-density lipoprotein cholesterol,higher total cholesterol,and an unhealthy diet were associated with higher risk of progression from S0 to S1.Being female,less than 60 years old,weekly physical activity,and vegetarian diet decreased this risk.Being female and less than 60 years old reduced the likelihood of transition from S1 to S2,whereas lower high-density lipoprotein cholesterol increased this likelihood.Conclusions:Following the occurrence of two complications in type 2 diabetes patients,the risk for accumulating a third complication within a short time is significantly increased.It is important to take advantage of the stable window period when patients have fewer than two complications,strengthen the monitoring of blood glucose and blood lipids,and encourage patients to maintain good living habits to prevent further deterioration.

From Diabetes to Diabetic Complications:Role of Autophagy

Diabetes and its complications reduce quality of life and are life-limiting.At present,diabetes treatment consists of hypoglycemic agents to control blood glucose and the use of insulin-sensitizing drugs to overcome insulin resistance.In diabetes,autophagy is impaired and thus there is poor intracellular environment homeostasis.Pancreaticβ-cells and insulin target tissues are protected by enhancing autophagy.Autophagy decreasesβ-cell apoptosis,promotesβ-cell proliferation,and alleviates insulin resistance.Autophagy in diabetes is regulated by the mammalian target of rapamycin(mTOR)/adenosine 5′-monophosphate(AMP)-activated protein kinase(AMPK)pathway and others.Autophagy enhancers can likely be used as a treatment for diabetes and its complications.This review examines the evidence linking autophagy to diabetes.

Recent therapeutic targets for the prevention and management of diabetic complications

Diabetes and associated complications represent major global public health issues which are associated with impaired quality of life and premature death.Although some diabetic complications have decreased in the developed world,the majority are still prevalent,with an increasing trend in the developing world.Currently used therapies are mainly‘glucocentric’,focusing on the optimization of glycemic control to prevent,delay or manage diabetes-associated complications-other common comorbidities,such as dyslipidemia and hypertension are often underestimated.Although a number of novel therapeutic approaches have been reported recently,some of them have not received comparable attention in relation to either further studies or potential clinical implementation.This editorial briefly discusses some recent therapeutic approaches to the prevention and management of diabetes and its associated complications,as well as potential directions for future research and development in this area.

Linking uric acid metabolism to diabetic complications

Hyperuricemia have been thought to be caused by the ingestion of large amounts of purines, and prevention or treatment of hyperuricemia has intended to prevent gout. Xanthine dehydrogenase/xanthine oxidase(XDH/XO) is rate-limiting enzyme of uric acid generation, and allopurinol was developed as a uric acid(UA) generation inhibitor in the 1950 s and has been routinely used for gout prevention since then. Serum UA levels are an important risk factor of disease progression for various diseases, including those related to lifestyle. Recently, other UA generation inhibitors such as febuxostat and topiroxostat were launched. The emergence of these novel medications has promoted new research in the field. Lifestyle-related diseases, such as metabolic syndrome or type 2 diabetes mellitus, often have a common pathological foundation. As such, hyperuricemia is often present among these patients. Many in vitro and animal studies have implicated inflammation and oxidative stress in UA metabolism and vascular injury because XDH/XO act as one of the major source of reactive oxygen species Many studies on UA levels and associated diseases implicate involvement of UA generation in disease onset and/or progression. Interventional studies for UA generation, not UA excretion revealed XDH/XO can be the therapeutic target forvascular injury and renal dysfunction. In this review, the relationship between UA metabolism and diabetic complications is highlighted.

Virtual screening of flavonoids from Jatropha gossypiifolia L.as potential drugs for diabetic complications

Background:Diabetes mellitus is a chronic metabolic disease that is a risk factor for epidemic pathologies.Under hyperglycemic conditions,the enzyme aldose reductase catalyzes the formation of sorbitol in the metabolism of glucose via polyols,leading to the development of diabetic complications.Therefore,inhibitors of this enzyme are therapeutic targets for the prophylaxis and treatment of these conditions.Methods:In this study,a generalized linear regression model was developed to analyze flavonoids-obtained from a database-that have been tested as inhibitors of aldose reductase.In this sense,the molecular descriptors implemented in DRAGON and MATLAB software were used to determine the correlation between the chemical structure of the inhibitors and their pharmacological activity.The model was validated according to the Organisation for Economic Co-operation and Development Standards and subsequently used for the virtual screening of the flavonoids identified in Jatropha gossypiifolia L.Results:The proposed model showed a good fit for its statistical parameters(R2=0.95).In addition,it showed good predictive power(R2 ext=0.94)and robustness(Q2 LOO=0.92).The experimental chemical space wherein the predictions were reliable(domain of application)was also defined.Finally,the model was used to identify 10 flavonoids from Jatropha gossypiifolia L.as candidates for natural drugs.Compounds with a low probability of oral absorption were identified,among which the elagic acid biflavonoid showed the greatest promise(pIC50 predicted=9.75).Conclusion:The Jatropha gossypiifolia L.species harbors flavonoids with high potential as inhibitors of the aldose reductase enzyme,in which the biflavonoid ellagic acid was shown to be the most promising inhibitor of the aldose reductase enzyme,suggesting its possible use in the treatment of the late complications of diabetes mellitus.

Knowledge, Attitude and Practice on Common Diabetic Patients among Diabetic Complications at Egyptian Hospital in Mogadishu, Somalia

Diabetes is a chronic illness that occurs when the pancreas stops producing insulin or when the body cannot use the produced insulin. Insulin is a hormone produced by the pancreas that helps glucose from meals enters the body’s cells for energy. The overall goal is to assess diabetes patients’ knowledge, attitudes, and behaviors about prevalent diabetic complications. This research used a descriptive qualitative methodology to assess diabetes complication knowledge, attitude, and practice. Ninety-eight diabetic patients were visiting the Egyptian Hospital in Mogadishu for four weeks. The data was collected using questionnaires. Finally, SPSS 20 was utilized for analysis. The research was performed from May to July 2020 with a non-probability sample size of 98 diabetics. The bulk of responders were aged 40 - 60 (36.7%). Type 2 was the most common (47.96%). 44.9% of respondents had diabetes for more than ten years. 60.2% had regular checkups, and 54.1 percent had therapy. 52% of participants were on a diet. 63.3% of respondents do not exercise often. However, most responders know the common issues (75%). Less than half of those polled had problems (41.8%). 22% incidence of Diabetic ketoacidosis. 78.6% of respondents know variables that decrease diabetes complications, whereas 22.4% do not. 37.8% of respondents saw a doctor for diabetes problems, whereas 62.2% did not. Diabetic patients’ knowledge, attitude, and practice were satisfactory for fundamental illness entanglements and self-testing. These findings may also be due to patient notification and, therefore, long-term illness that leads them to get acquainted with things alone. However, the tendency for regular exercise was low, which may produce more specific consequences of illness. Conclusion: We find that DM patients’ KAP was adequate in terms of knowledge of diabetic complications. These results may explain the patients’ long-standing illness, which forces them to discover things independently. At the same time, just a handful of them were familiar with vasculopathy and cardiovascular disorders. However, the researchers discovered low level of attitudes and practice toward regular exercise and insufficient levels of attitudes and practice toward diet management and treatment adherence. In general, this degree of KAP is suboptimal and requires further assessment of KAP obstacles in Somalia.

Mitigating diabetes-related complications:Empowering metformin with cholecalciferol and taurine supplementation in type 2 diabetic rats

BACKGROUND Type 2 diabetes is one of the most prevalent chronic diseases worldwide,significantly impacting patients'quality of life.Current treatment options like metformin(MET)effectively counteract hyperglycemia but fail to alleviate diabetes-associated complications such as retinopathy,neuropathy,nephropathy,hepatopathy,and cardiovascular diseases.AIM To propose the supplementation of cholecalciferol(CHO)and taurine(TAU)to enhance MET efficacy in controlling diabetes while minimizing the risk of associated complications.METHODS The study involved sixty rats,including ten non-diabetic control rats and fifty experimental rats with type 2 diabetes induced by streptozotocin.The experimental rats were further subdivided into positive control and treatment subgroups.The four treatment groups were randomly allocated to a single MET treatment or MET combined with supplements either CHO,TAU,or both.RESULTS Diabetic rats exhibited elevated levels of glucose,insulin,Homeostasis Model Assessment of Insulin Resistance(HOMA-IR),glycated hemoglobin percentage,lipid markers,aspartate aminotransferase,and malondialdehyde,along with reduced levels of antioxidant enzymes(catalase and superoxide dismutase).The administration of CHO and TAU supplements alongside MET in diabetic rats led to a noticeable recovery of islet mass.The antioxidative,anti-inflammatory,and anti-apoptotic properties of the proposed combination therapy significantly ameliorated the aforementioned abnormalities.CONCLUSION The supplementation of CHO and TAU with MET showed the potential to significantly improve metabolic parameters and protect against diabetic complications through its antioxidative,anti-inflammatory,and antiapoptotic effects.

Potential mechanism of teneligliptin in the treatment of diabetic cardiomyopathy

Diabetic cardiomyopathy(DCM),a complication of diabetes,poses a significant threat to public health,both its diagnosis and treatment presents challenges.Teneligliptin has promising applications and research implications in the treat-ment of diabetes mellitus.Zhang et al observed the therapeutic effect of tenelig-liptin on cardiac function in mice with DCM.They validated that teneligliptin’s mechanism of action in treating DCM involves cardiomyocyte protection and inhibition of NLRP3 inflammasome activity.Given that the NLRP3 inflammasome plays a crucial role in the onset and progression of DCM,it presents a promising therapeutic target.Nevertheless,further clinical validation is required to ascertain the preventive and therapeutic efficacy of teneligliptin in DCM.

Effects of vitamin family members on insulin resistance and diabetes complications

The following letter to the editor highlights the article“Effects of vitamin D supplementation on glucose and lipid metabolism in patients with type 2 diabetes mellitus and risk factors for insulin resistance”in World J Diabetes 2023 Oct 15;14(10):1514-1523.It is necessary to explore the role of vitamin family members in insulin resistance and diabetes complications.

Therapeutic Effect of Intragastric Administration of Jiangtang Shuxin Recipe Suspension on Diabetic Heart Failure in Rats and Its Mechanism

[Objectives]To observe the therapeutic effect of intragastric administration of Jiangtang Shuxin recipe on diabetic heart failure(DHF)in rats and to explore its mechanism.[Methods]Fifty SD rats were randomly divided into five groups,with 10 rats in each group.DHF models were prepared in the low-dose group,high-dose group,Western medicine group,and model group except the control group.Rats in the low-dose and high-dose groups were given 1.0 and 1.5 g/(kg·d)Jiangtang Shuxin recipe suspension by gavage,respectively.Rats in the Western medicine group were given gliquidone and benazepril by gavage for 2 months,and were fed with high-fat diet.Rats in the control group were fed with ordinary diet.Fasting blood glucose(FBG),serum triglyceride(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),C-reactive protein(CRP),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),creatine kinase isoenzyme(CK-MB),lactate dehydrogenase(LDH),pathological morphology of myocardial tissue,NF-κB p65 protein and IκBαprotein were compared among groups.[Results]Compared with the control group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH increased,while the level of serum HDL-C decreased.The myocardial tissue was seriously damaged,and the expression of NF-κB p65 protein increased,while the expression of IκBαprotein decreased in the other four gruops(all P<0.05).Compared with the model group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH decreased,while the serum HDL-C level increased.The myocardial tissue damage was alleviated,and the expression of NF-κB p65 protein decreased,while the expression of IκBαprotein increased in the low-dose group,high-dose group and Western medicine group(all P<0.05).Compared with the Western medicine group,the levels of FBG,serum TG,LDL-C,CRP,IL-6,TNF-α,CK-MB and LDH decreased,and the level of serum HDL-C increased in the high-dose group(all P<0.05).[Conclusions]Jiangtang Shuxin recipe has a therapeutic effect on DHF in rats,with the best effect in the high-dose group.It can not only alleviate high glucose and high fat state,but also reduce myocardial injury and inflammation,and improve the pathological morphology of myocardial cells.The mechanism may be related to its inhibition of NF-кB signaling pathway.

Research progress of artesunate in diabetes and its complications

Diabetes is a metabolic disease characterized by abnormally elevated blood glucose levels.Persistent hyperglycemia leads to diabetic nephropathy,diabetic retinopathy,diabetes with periodontal disease and other diabetic complications.These diseases have become the main causes of disability and death in diabetic patients.Artesunate is well known as an antimalarial drug for controlling malaria symptoms.Current studies have shown that artesunate improves diabetes and its complications by protecting islet cells,improving glucose and lipid metabolism,anti-inflammatory and immune regulation.Based on the research status in recent years,this paper focuses on the mechanism of artesunate in diabetes and its complications,to provide a theoretical basis for future diabetes research.

Antiglycating effects of citrus flavonoids and associated mechanisms

Glycation of proteins and DNA forms advanced glycation end products(AGEs)causing cell and tissue dysfunction and subsequent various chronic diseases,in particular,metabolic and age-related diseases.Targeted AGE inhibition includes scavengers of reactive carbonyl species(RCS)such as methylglyoxal(MG),glyoxalase-1 enhancers,Nrf2/ARE pathway activators,AGE/RAGE formation inhibitors and other antiglycatng agents.Citrus flavonoids have demonstrated antioxidant and anti-inflammatory effects and are also found to be effective antiglycating agents.Herein,we reviewed the up to date progress of the antiglycation effects of citrus flavonoids and associated mechanisms.Major citrus flavonoids,hesperedin and its aglycone,hesperetin,inhibited glycation by scavenging MG forming mono-or di-flavonoid adducts with MG,enhanced the activity of glyoxase-1,activated Akt/Nrf2 signal pathway while inhibiting AGE/RAGE/NF-κB pathway,reduced the formation of Nε-(carboxylmethyl)lysine(CML)and pentosidine,inhibited aldol reductase activity and decreased the levels of fructosamine.The antiglycating activity and mechanisms of other flavonoids was also summarized in this review.In conclusion,citrus flavonoids possess effective antiglycating activity via different mechanisms,yet there are many challenging questions remaining to be studied in the near future such as in vivo testing and human study of citrus flavonoids for efficacy,effectiveness and adverse effects of citrus flavonoids as a functional food in managing high levels of AGEs and controlling AGE-induced chronic diseases,diabetic complications in particular.

Efficacy of epalrestat plus α-lipoic acid combination therapy versus monotherapy in patients with diabetic peripheral neuropathy: a meta-analysis of 20 randomized controlled trials

OBJECTIVE： To evaluate the efficacy of α-lipoic acid（ALA） plus epalrestat combination therapy in the treatment of diabetic peripheral neuropathy（DPN）. DATA SOURCES： The electronic databases of Pub Med, Medline, Embase, the Cochrane Library, the Chinese National Knowledge Infrastructure, the Wanfang Database and the Chinese Biomedical Database were used to retrieve relevant studies without language restrictions. The search was conducted from the inception of each database to 7 October 2016. The key terms were（diabetic peripheral neuropathy or diabetic neuropathy or DPN） AND（α-lipoic acid or lipoic acid or thioctic acid） AND epalrestat. DATA SELECTION： All of the eligible studies met the following inclusion criteria：（1） Randomized controlled trials that compared efficacy and safety of epalrestat plus ALA combination therapy versus epalrestat or ALA monotherapy in patients with DPN.（2） The minimum duration of treatment was 2 weeks.（3） The DPN patients were diagnosed using the World Health Organization standardized type 2 diabetes mellitus and DPN criteria.（4） Studies contained at least one measure that could reflect the efficacy of the drug and nerve conduction velocities. Studies in which the control group used epalrestat or ALA combined with other drugs were excluded. Statistical analyses were performed using STATA software for meta-analysis. OUTCOME MEASURES： The primary outcomes were the therapeutic efficacy, median motor nerve conduction velocity（MNCV）, median sensory nerve conduction velocity（SNCV）, peroneal MNCV and peroneal SNCV.RESULTS： Twenty studies with 1894 DPN patients were included, including 864 patients in the ALA plus epalrestat group, 473 in the ALA group and 557 in the epalrestat group. The efficacy of ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies（RR = 1.29, 95% CI： 1.21–1.38; RR = 1.43, 95% CI： 1.34–1.54, respectively）. ALA plus epalrestat combination therapy also significantly improved median MNCV（WMD = 5.41, 95% CI： 2.07–8.75）, median SNCV（WMD = 5.87, 95% CI： 1.52–10.22）, peroneal MNCV（WMD = 5.59, 95% CI： 2.70–8.47） and peroneal SNCV（WMD = 4.57, 95% CI： 2.46–6.68）.CONCLUSION： ALA plus epalrestat combination therapy was superior to ALA and epalrestat monotherapies for clinical efficacy and nerve conduction velocities in patients with DPN.

Treatment with NADPH oxidase inhibitor apocynin alleviates diabetic neuropathic pain in rats

Increased reactive oxygen species by the activation of NADPH oxidase（NOX） contributes to the development of diabetic complications.Apocynin,a NOX inhibitor,increases sciatic nerve conductance and blood flow in diabetic rats.We investigated potential protective effect of apocynin in rat diabetic neuropathy and its precise mechanism of action at molecular level.Rat models of streptozotocin-induced diabetes were treated with apocynin（30 and 100 mg/kg per day,intragastrically） for 4 weeks.Mechanical hyperalgesia and allodynia were determined weekly using analgesimeter and dynamic plantar aesthesiometer.Western blot analysis and histochemistry/immunohistochemistry were performed in the lumbar spinal cord and sciatic nerve respectively.Streptozotocin injection reduced pain threshold in analgesimeter,but not in aesthesiometer.Apocynin treatment increased pain threshold dose-dependently.Western blot analysis showed an increase in catalase and NOX-p47 phox protein expression in the spinal cord.However,protein expressions of neuronal and inducible nitric oxide synthase（n NOS,i NOS）,superoxide dismutase,glutathion peroxidase,nitrotyrosine,tumor necrosis factor-α,interleukin-6,interleukin-1β,aldose reductase,cyclooxygenase-2 or MAC-1（marker for increased microgliosis） in the spinal cord remained unchanged.Western blot analysis results also demonstrated that apocynin decreased NOX-p47 phox expression at both doses and catalase expression at 100 mg/kg per day.Histochemistry of diabetic sciatic nerve revealed marked degeneration.n NOS and i NOS immunoreactivities were increased,while S-100 immunoreactivity（Schwann cell marker） was decreased in sciatic nerve.Apocynin treatment reversed these changes dose-dependently.In conclusion,decreased pain threshold of diabetic rats was accompanied by increased NOX and catalase expression in the spinal cord and increased degeneration in the sciatic nerve characterized by increased NOS expression and Schwann cell loss.Apocynin treatment attenuates neuropathic pain by decelerating the increased oxidative stress-mediated pathogenesis in diabetic rats.

Rapid correction of chronic hyperglycemia and bone remodeling,warning against overdoing

It is widely recognized that chronic hyperglycemia decreases bone quality,although little is known about the impact of the rapid correction of chronic hyperglycemia on the quality of bone remodeling.This spotlight article explores this correlation by focusing on the stages of bone remodeling linked to glucose levels.

Licorice and its main components on the treatment of diabetes and its complications:A review of in vivo and in vitro studies

Licorice is one of the oldest herbal medicines for its various ethno pharmacological uses.In both Asian and European countries,it has been recorded for treatment of inflammatory diseases.A large number of ingredients have been isolated from licorice,including triterpene saponins and flavonoids,which are normally being considered to be the main biologically active components.In the last decade,licorice has been proved exert anti-diabetic effect in various in vivo and in vitro models of diabetes mellitus.Furthermore,licorice can also antagonize all sorts of diabetes complications,including diabetic nephropathy,atherosclerosis,diabetic retinopathy and neuropathy.Except anti-inflammation,licorice and its active components show anti-diabetic effects by improving insulin resistance and increasing insulin secretion,regulating lipid metabolism,and anti-oxidation.The useful effects of licorice and its active components are due to regulating different pathways and proteins,including NF-κB,AMPK,insulin signaling pathway,MAPK,etc.In this review,we provide an overview of the beneficial effects and related molecular mechanism of licorice and its effective components on improving diabetes and its complications.

Mechanism of Gegen Qinlian Decoction in Treating Type 2 Diabetes Mellitus Complicated with NAFLD Based on Network Pharmacology

[Objectives]To explore the mechanism of Gegen Qinlian Decoction in treating type 2 diabetes mellitus(T2DM)complicated with non-alcoholic fatty liver disease(NAFLD)by analyzing the effective components of Gegen Qinlian Decoction.[Methods]TCMSP database was used to analyze the active components of Gegen Qinlian Decoction,and pubchem and Swiss ADME databases were also used to predict drug targets,extract T2DM complicated with NAFLD targets from OMIM and Genecards databases.Venny plot was drawn to obtain intersection targets,and finally Cytoscape was used to make core target maps and drug-target-disease network maps.Using DAVID and Metascape database to analyze the intersection targets,the gene ontology information of Go and KEGG was obtained.Microbial informatics technology was used to visualize GO,and Cytoscape was used to make drug-target-disease network map-enrichment pathway map.[Results]The network pharmacological analysis showed that Gegen Qinlian Decoction acted on the key targets of type 2 diabetes mellitus complicated with non-alcoholic fatty liver disease,such as ALB and ALT1,through many components,and achieved the purpose of treating this disease.The chemical constituents of the drug include formononetin,5-hydroxyisomucronulatol-2,5-2-O-glucoside,cholesteryl laurate,isoliquiritigenin,etc.[Conclusions]This study provides a new idea and theoretical support for future drug research and clinical practice.

Adropin as an indicator of T2DM and its complications

Type 2 diabetes mellitus(T2 DM)is one of metabolic diseases with the major inducer of obesity.Due to the change in lifestyle and dietary structure,more and more people are being suffered from T2 DM.Therefore,the prevention and treatment of T2 DM and its complications has become an urgent problem to be solved.As a secreted peptide,adropin is identifi ed as a useful regulator associated with insulin sensitivity and energy homeostasis.It has the potential for regulating metabolic diseases including obesity and T2 DM.It should be noted that the secretion of adropin can be induced by diets,aerobic exercise and other interventions.In this article,the underlying mechanisms of adropin for regulating obesity,T2 DM and its complications including diabetic nephropathy,diabetic retinopathy,diabetic encephalopathy,diabetic vascular disease and diabetic cardiovascular disease were summarized.Meanwhile,the strategies for promoting the secretion of adropin were also discussed,which will provide a target for the prevention and targeted treatment,or a candidate of novel and effective functional food or drug for metabolic diseases in the future.

Comparing the incidence of major cardiovascular events and severe microvascular complications in patients with type 2 diabetes mellitus:A systematic review and meta-analysis

BACKGROUND Type 2 diabetes mellitus(T2DM)causes both macrovascular and microvascular complications.However,currently,selection of glycemic measures and their thresholds to diagnose T2DM,and efficacy outcomes in evaluation of anti-diabetic drugs is predominantly informed by the relation of T2DM to microvascular complications.We can be severely mistaken on T2DM by neglecting macrovascular complications which are generally more severe,if they also occur more commonly than microvascular complications.AIM To compare the incidence of major cardiovascular events(MACEs)and severe microvascular complications(SMICs)in T2DM patients.METHODS MEDLINE,EMBASE,and Cochrane Central Register of Controlled Trials were searched from inception to September 2017.Cohort studies or trials of T2DM patients aged 18 years or older that reported incidence of both MACEs and SMICs were included.MACEs were defined as nonfatal myocardial infarction and stroke,and cardiovascular death,while SMICs included serious retinopathy,nephropathy and diabetic disorder.The relative risk(RR)was estimated as the incidence of MACEs divided by that of SMICs in same patients and combined with meta-analysis in a random-effect model.RESULTS Twelve studies with a total of 16 cohorts and 387376 patients were included,and the combined RR was 2.02(95%CI:1.46–2.79).The higher incidence of MACEs remained in various subgroup and sensitivity analyses.CONCLUSION Patients with T2DM are much more likely to develop MACEs than SMICs.By taking more serious consequences and relatively higher incidence into consideration,macrovascular complications deserve more emphasis in developing the diagnostic criteria of T2DM and in evaluating the efficacy of antidiabetic drugs.

Antidiabetic agents:Do they hit the right targets?

Diabetes mellitus(DM)is a progressive metabolic disease characterized by chronic hyperglycemia and caused by different degree of pancreatic islet dysfunction and/or insulin resistance(IR).Long course DM can lead to a variety of macrovascular and microvascular complications which involve artery vessels,heart,kidney,retina,nervous system,etc.In recent years,DM has attracted more and more attention due to its high morbidity and mortality.In addition to achieve effective glycemic control,prevention of complications has also been considered a priority for type 2 diabetes mellitus(T2DM)management.Herein,we provide a comprehensive overview on the pharmacotherapeutics for T2DM and perspectives on the future directions of basic and translational research on anti-diabetic therapy and pharmatheutical development of new drugs.