Acute worsening of microvascular complications of diabetes mellitus during rapid glycemic control:The pathobiology and therapeutic implications

While chronic hyperglycaemia resulting from poorly controlled diabetes mellitus(DM)is a well-known precursor to complications such as diabetic retinopathy,neuropathy(including autonomic neuropathy),and nephropathy,a paradoxical intensification of these complications can rarely occur with aggressive glycemic management resulting in a rapid reduction of glycated haemoglobin.Although,acute onset or worsening of retinopathy and treatment induced neuropathy of diabetes are more common among these complications,rarely other problems such as albuminuria,diabetic kidney disease,Charcot’s neuroarthropathy,gastroparesis,and urinary bladder dysfunction are also encountered.The World Journal of Diabetes recently published a rare case of all these complications,occurring in a young type 1 diabetic female intensely managed during pregnancy,as a case report by Huret et al.It is essential to have a comprehensive understanding of the pathobiology,prevalence,predisposing factors,and management strategies for acute onset,or worsening of microvascular complications when rapid glycemic control is achieved,which serves to alleviate patient morbidity,enhance disease management compliance,and possibly to avoid medico-legal issues around this rare clinical problem.This editorial delves into the dynamics surrounding the acute exacerbation of microvascular complications in poorly controlled DM during rapid glycaemic control.

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.

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.

Prevalence of Microvascular Complications and Associated Risk Factors among Diabetes Mellitus Patients Attending Nyeri County Referral Hospital, Kenya: A Cross-Sectional Study

Microvascular complications are one of the major causes of morbidity and mortality worldwide among patients with diabetes mellitus (DM). More than 50% of Nyeri County Referral Hospital (NCRH) admissions result from non-communicable diseases (NCDs) and over 55% of hospital deaths are attributable to NCDs. In Kenya, Nyeri County has the highest prevalence of diabetes mellitus compared to other counties. This study therefore sought to assess the prevalence of microvascular complications and the associated risk factors among patients attending Nyeri County Referral Hospital in Kenya. A hospital-based cross-sectional study was conducted on 314 DM patients on follow-up at NCRH from August 2022 to October 2022. Data were analyzed using STATA version 17. Univariate and multivariate logistic regression analyses are used to determine the risk factors associated with Microvascular complications of DM. Among the 314 participants with DM, 58% were females. The overall prevalence of Microvascular complications (MVCs) is 36.62%. Diabetic peripheral neuropathy was the most frequent complication (27.4%). Inadequate physical exercise was a risk factor for all MVCs. Age, marital status, and level of education were risk factors for neuropathy while smoking and alcohol intake were risk factors for nephropathy. Non-smokers were 98% less likely to have nephropathy (OR = 0.024;95% CI 0.003 - 0.145). The odds of those who exercise once weekly getting retinopathic complications reduced by 83% (OR = 0.18, 95% CI 0.049 - 0.398) compared to those who exercise daily. The findings highlight the implication of lifestyle factors in the development of MVCs among DM patients. Therefore, benefits of microvascular complications prevention should thus be factored into the management of patients with diabetes mellitus.

Acute Metabolic Complications of Diabetes in the Oueme-Plateau Provincial Teaching Hospital: Epidemiological, Clinical, Paraclinical and Evolutionary Aspects

Introduction: Diabetes mellitus, a metabolic disease, is now an important public health problem across the world. Our aim was to study the epidemiological, clinical, paraclinical, and evolutionary aspects of acute metabolic complications (AMC) of diabetes in the endocrinology department of the Oueme-Plateau Provincial Teaching Hospital. Methods: This was a descriptive cross-sectional study with data collection based on the medical records of patients presenting with acute metabolic complications of diabetes in the endocrinology department of the Oueme-Plateau Provincial Teaching Hospital during the 3 years study period (from January 2020 to December 2022). Results: Over 788 patients hospitalized during the study period, 157 had an acute metabolic complication of diabetes, which is a hospital prevalence of 19.9%. Among these 157 cases, 140 were suitable for analysis and therefore constituted our study sample. The mean age of the patients was 49.9 ± 14.7 years, with 19 as minimum and 90 years as maximum. Most of them were women (52.4%). Hypertensive diabetics accounted for 54.9% of cases. Ketoacidosis was the most common complication (62.1%), followed by hyperosmolar hyperglycemic syndrome (23.6%) and hypoglycemia (14.3%). Infection (69.3%) and therapeutic noncompliance (22.9%) were the most common triggers. The average length period of their hospital stay was 7.1 ± 5.1 days, and the outcome was satisfactory in 87.9% of the cases. Unfortunately, there were 3.6% deaths during hospitalization. Conclusion: Acute metabolic complications of diabetes were dominated by ketoacidosis. Infection was the dominant factor in decompensation. Therapeutic education of diabetic patients as well as clinical and biological monitoring must be more stringent and rigorous.

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.

Prevalence and risk factors of wound complications after transtibial amputation in patients with diabetic foot

BACKGROUND Diabetic foot(DMF)complications are common and are increasing in incidence.Risk factors related to wound complications are yet to be established after transtibial amputation under the diagnosis of DMF infection.AIM To analyze the prognosis and risk factors related to wound complications after transtibial amputation in patients with diabetes.METHODS This retrospective cohort study included seventy-two patients with DMF complications who underwent transtibial amputation between April 2014 and March 2023.The groups were categorized based on the occurrence of wound complications,and we compared demographic data between the complication group and the non-complication group to analyze risk factors.Moreover,a multivariate logistic regression analysis was performed to identify risk factors.RESULTS The average follow-up period was 36.2 months.Among the 72 cases,31(43.1%)had wound complications.Of these,12 cases(16.7%)received further treatment,such as debridement,soft tissue stump revision,and re-amputation at the proximal level.In a group that required further management due to wound complications after transtibial amputation,the hemoglobin A1c(HbA1c)level was 9.32,while the other group that did not require any treatment had a 7.54 HbA1c level.The prevalence of a history of kidney transplantation with wound complications after transtibial amputation surgery in DMF patients was significantly greater than in cases without wound complications(P=0.02).Other factors did not show significant differences.CONCLUSION Approximately 43.1%of the patients with transtibial amputation surgery experienced wound complications,and 16.7%required additional surgical treatment.High HbA1c levels and kidney transplant history are risk factors for postoperative wound complications.

Role of angiotensin receptor-neprilysin inhibitor in diabetic complications

Diabetes mellitus is a prevalent disorder with multi-system manifestations,causing a significant burden in terms of disability and deaths globally.Angio-tensin receptor-neprilysin inhibitor(ARNI)belongs to a class of medications for treating heart failure,with the benefits of reducing hospitalization rates and mortality.This review mainly focuses on the clinical and basic investigations related to ARNI and diabetic complications,discussing possible physiological and molecular mechanisms,with insights for future applications.

Regulatory role of peroxynitrite in advanced glycation end products mediated diabetic cardiovascular complications

The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling mediators.The effect of superoxide(O2-)and O2-mediated ROS and reactive nitrogen species depends on their concentration and location of formation.Nitric oxide(NO)has anti-inflammatory and anticoagulant properties and a vasodilation effect,but NO can be deactivated by reacting with O_(2)^(-).This reaction between NO and O2-produces the potent oxidant ONOO−.Therefore,ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.

Ocular Complications in Diabetic Patients: Prevalence, Impact on Quality of Life, and Implications for Healthcare

Introduction: Diabetes, a chronic disease characterized by persistent hyperglycemia, poses a major global health challenge. In Gabon, 10% of the population is affected by this condition, highlighting the need to actively understand and manage it. Ocular complications of diabetes, including diabetic retinopathy, glaucoma, and cataracts, have a devastating impact on patients quality of life and represent a crucial issue for healthcare systems. Methodology: This study conducted in Libreville from February 9, 2022, to April 15, 2022, was cross-sectional, longitudinal, and descriptive, with prospective data collection. Participants were diabetic patients regularly followed in the endocrinology department of CHUL, who were referred for a comprehensive ophthalmological examination at CHUO. Sampling was exhaustive, with strict inclusion criteria aimed at ensuring the representativeness of the study population. Results: The mean age of participants was 57.5 ± 13.2 years with a male-to-female ratio of 0.8. Personal histories were dominated by hypertension, while family histories were dominated by diabetes. Ocular complications of diabetes included refractive disorders (78.9%), cataracts (31.7%), glaucoma (78.9%), and diabetic retinopathy (13.7%). These ocular complications had a significant impact on participants’ quality of life, leading to impaired vision (78.9%), difficulties in carrying out daily activities (62.2%), the need for caregiver assistance (50.3%), high levels of stress and anxiety (68.9%), regular medication intake (71.4%), adherence to a specific diet (55.9%), and frequent blood glucose monitoring (74.5%). Conclusion: This study highlights the major impact of diabetic ocular complications on patients’ quality of life.

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.

Ocular complications of diabetes mellitus

Diabetes mellitus(DM) is a important health problem that induces ernestful complications and it causes significant morbidity owing to specific microvascular complications such as, retinopathy, nephropathy and neuropathy, and macrovascular complications such as, ischaemic heart disease, and peripheral vasculopathy. It can affect children, young people and adults and isbecoming more common. Ocular complications associated with DM are progressive and rapidly becoming the world's most significant cause of morbidity and are preventable with early detection and timely treatment. This review provides an overview of five main ocular complications associated with DM, diabetic retinopathy and papillopathy, cataract, glaucoma, and ocular surface diseases.

Gastrointestinal complications of diabetes mellitus

Diabetes mellitus affects virtually every organ system in the body and the degree of organ involvement depends on the duration and severity of the disease,and other co-morbidities.Gastrointestinal(GI) involvement can present with esophageal dysmotility,gastro-esophageal reflux disease(GERD),gastroparesis,enteropathy,non alcoholic fatty liver disease(NAFLD) and glycogenic hepatopathy.Severity of GERD is inversely related to glycemic control and management is with prokinetics and proton pump inhibitors.Diabetic gastroparesis manifests as early satiety,bloating,vomiting,abdominal pain and erratic glycemic control.Gastric emptying scintigraphy is considered the gold standard test for diagnosis.Management includes dietary modifications,maintaining euglycemia,prokinetics,endoscopic and surgical treatments.Diabetic enteropathy is also common and management involves glycemic control and symptomatic measures.NAFLD is considered a hepatic manifestation of metabolic syndrome and treatment ismainly lifestyle measures,with diabetes and dyslipidemia management when coexistent.Glycogenic hepatopathy is a manifestation of poorly controlled type 1 diabetes and is managed by prompt insulin treatment.Though GI complications of diabetes are relatively common,awareness about its manifestations and treatment options are low among physicians.Optimal management of GI complications is important for appropriate metabolic control of diabetes and improvement in quality of life of the patient.This review is an update on the GI complications of diabetes,their pathophysiology,diagnostic evaluation and management.

Toxic stress,inflammation and symptomatology of chronic complications in diabetes

Diabetes affects at least 382 million people worldwide and the incidence is expected to reach 592 million by 2035.The incidence of diabetes in youth is skyrocketing as evidenced by a 21% increase in type 1 diabetes and a 30.5% increase in type 2 diabetes in the United States between 2001 and 2009.The effects of toxic stress,the culmination of biological and environmental interactions,on the development of diabetes complications is gaining attention.Stress impacts the hypothalamus-pituitaryadrenal axis and contributes to inflammation,a keybiological contributor to the pathogenesis of diabetes and its associated complications.This review provides an overview of common diabetic complications such as neuropathy,cognitive decline,depression,nephropathy and cardiovascular disease.The review also provides a discussion of the role of inflammation and stress in the development and progression of chronic complications of diabetes,associated symptomatology and importance of early identification of symptoms of depression,fatigue,exercise intolerance and pain.

Clinical Features and Microvascular Complications Risk Factors of Early-onset Type 2 Diabetes Mellitus

The aim of this research was to study the clinical features and microvascular complications risk factors of early-onset type 2 diabetes mellitus(T2DM).We analyzed the clinical data from 1421 T2DM inpatients at Wuhan Union Hospital.Subjects were divided into early-onset T2DM group(diagnostic age<40 years)and late-onset T2DM group(diagnostic age>40 years).All subjects underwent a standardized assessment of microvascular complications.Data were compared with independent-samples t test or Chi-square test.Multiple logistic regression was used to determine the risk factors of microvascular complications.Patients with early-onset T2DM were more inclined to have a lower systolic blood pressure(SBP),a longer duration of diabetes and higher levels of body mass index(BM1),uric acid(UA),fasting plasma glucose(FPG),total cholesterol(TC),triglyceride(TG)and glycosylated hemoglobin(HbAlc)than those with lateonset T2DM(P<0.05).The prevalence of diabetic retinopathy(DR)was significantly higher and that of diabetic peripheral neuropathy(DPN)was significantly lower in early-onset group than in late-onset group(P<0.05).For DN,UA was an independent risk factor in early-onset T2DM.SBP and TG were independent risk factors in late-onset T2DM.For DR,duration of diabetes and SBP were independent risk factors in early-onset T2DM.Duration of diabetes,SBP and HbAlc were independent risk factors in late-onset T2DM.This study demonstrated that the clinical characteristics of early-onset T2DM were metabolic disorders,including glucose metabolism,lipid metabolism and amino acid metabolism.Early-onset T2DM was more likely to be associated with DR.The potential pathogenesis of early and late-onset T2DM might be different.The management of metabolic risk factors especially HbA1c,SBP,TG and UA is advised to be performed in the early stage of diabetes.

Effects of intensive control of blood glucose and blood pressure on microvascular complications in patients with type Ⅱ diabetes mellitus

AIM: To evaluate the effects of intensive control of blood glucose and blood pressure on microvascular complications in patients with type Ⅱ diabetes by comparing the therapeutic effects of intensive and standard treatment in patients with type Ⅱ diabetes. METHODS: A total of 107 patients with type Ⅱ diabetes were randomly assigned into intensive and standard treatment groups. Patients in the intensive treatment group received preterax (perindopril/ indapamide) to control blood pressure, and gliclazide (diamicron) MR to control blood glucose. Patients in the standard treatment group received routine medications or placebo. Urinary microalbumin (UMA), urinary creatinine (UCR), the UMA/ UCR ratio, and visual acuity were monitored according to the study design of the ADVANCE trial. Direct ophthalmoscopy and seven-field stereoscopic retinal photography were used to examine the fundi at baseline,and repeated after 5 years of treatment. RESULTS: The characteristics of patients in both groups were well balanced at baseline. After 5 years of treatment, visual acuity was found to be decreased in the standard group (P=0.04), but remained stable in the intensive group. The severity of diabetic retinopathy had not progressed in patients in the intensive group, but had deteriorated in the standard group (P=0.0006). The UMA/UCR ratio was not obviously changed in patients in the intensive group, whereas it was significantly increased in the standard group (P=0.00). CONCLUSION: Intensive control of blood glucose and blood pressure can decrease the incidence or slow the progression of microvascular complications in patients with type Ⅱ diabetes, and maintain stable vision.

Phenolic composition and inhibitory activity of Mangifera indica and Mucuna urens seeds extracts against key enzymes linked to the pathology and complications of type 2 diabetes

Objective:To investigate the phenolic compounds composition and the inhibitory activity of Mangifera indica(M.indica) and Mucuna urens(M.urens) seeds extracts against some key enzymes(-amylase,-glucosidasc and aldose reductase) implicated in the pathology and complications of type 2 diabetes in vitro.Methods:Reverse phase chromatographic quantification of the major flavonoids and phenolic acids in the seeds extracts was carried out using high performance liquid chromatography coupled with diode array detection.The inhibitory activities of the seeds extracts against-amylase and-glucosidase were estimated using soluble starch and p-nitrophenylglucopyranosidc as their respective substrates.Inhibition of aldose reductase activity by the extracts was assayed using partially purified lens homogenate of normal male rat as source of enzyme;inhibition of Fe^(2+)-induced lipid peroxidation by extracts was tested in rat pancreas homogenate.Results:The chromatography result revealed that extracts of both seeds had appreciable levels of some major flavonoids and phenolic acids of pharmacological importance,including gallic acid,chlorogenic acid,caffeic acid,ellagic acid,catechin,rutin,quercitrin.quercetin and kaempferol.Extracts of both seeds effectively inhibited-amylase,-glucosidase and aldose reductase activities in a dose-dependent manner,having inhibitory preference for these enzymes in the order of aldose reductase>-glucosidase>-amylase.With lower half-maximal inhibitory concentrations(IC50)against-amylase,-glucosidase,and aldose reductase,M.indica had stronger inhibitory potency against these enzymes than M.urens.Extracts of both seeds also inhibited Fe2+-induced lipid peroxidation in a dose-dependent pattern,with M.indica being more potent than M.urens.Conclusions:The results obtained provide support for a possible use of M.indica and M.urens seeds in managing hyperglycemia and preventing the complications associated with it in type 2diabetes.

Asymmetric dimethylarginine, a biomarker of cardiovascular complications in diabetes mellitus

Cardiovascular(CV) complications are an essential causal element of prospect in diabetes mellitus(DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or cerebral infarction in DM subjects. From another point of view, asymmetric dimethylarginine(ADMA) has been established as an inhibitor of endogenous nitric oxide synthesis and the relationship between ADMA and arteriosclerosis has been reported. In our study with 87 type 2 DM(T2DM) patients, we have examined whether ADMA and other CV risk factors are the useful predictors of DMCV complications. After the measurement of the respective CV risk factors, we have followed the enrolled T2 DM patients for 5 years. We have finally analyzed 77 patients. DMCV complications developed in 15 cases newly within 5 years, and 4 cases recurred. The concentrations of ADMA in plasma were markedly more elevated in 19 DM patients with CV complications than in 58 DM patients without CV complications. Urinary albumin(U-Alb), mean intimal-medial thickness(IMT) and ankle brachial index(ABI) were also higher in patients with CV complications. Multiple regression analyses showed that U-Alb had an influence on the high level of ADMA(standardized β = 6.59, P = 0.00014) independently of age, systolic BP, fibrinogen, mean IMT, plaque score, and ABI. The review indicates what is presently known regarding plasma ADMA that might be a new and meaningful biomarker of CV complications in DM subjects.

Relationship between lipoprotein （a） and micro/macro complications in type 2 diabetes mellitus： a forgotten target

Objectives Increased lipoprotein （a） serum concentration seems to be a cardiovascular risk factor; this has not been confirmed in extracoronary atherosclerosis complications. We therefore wished to gain a deeper insight into relationship between the plasma concentrations of lipoprotein （a） and the micro- and macro-vascular complications of type 2 diabetes mellitus and to identify possible differences in this association. Methods This is a descriptive observational cross-sectional study. Two-hundred and seventeen elderly patients with type 2 diabetes mellitus were included from the internal medicine outclinic. Anthropometric data, analytical data （insulin reserve, basal and postprandial peptide C, glycosylated hemoglobin, renal parameters, lipid profile and clinical data as hypertension, obesity, micro and macrovascular complications were collected. Results Patients were grouped according to the type 2 diabetes mellitus time of evolution. The mean plasma concentration of lipoprotein （a） was 22.2± 17.3 mg/dL （22.1± 15.9 mg/dL for males, and 22.1 ± 18.4 mg/dL for females）. Patients with hypertension, coronary heart disease, cerebrovascular accident, microalbuminuria and proteinuria presented a statistically significant increased level of lipoprotein （a）. Similarly, the patients with hyperlipoprotein （a） （≥30 mg/dL） presented significantly increased levels of urea and total cholesterol. In the multivariate regression model, the level of lipoprotein （a） is positively correlated with coronary heart disease and diabetic nephropathy （P 〈 0.01 and P 〈 0.005, respectively）. Conclusions The elevation of plasma levels of lipoprotein （a） are associ- ated with the development of coronary heart disease and diabe tic nephropathy. Therefore, we consider that the determination of lipoprotein （a） may be a prognostic marker of vascular complications in patients with type 2 diabetes mellitus.

Prevention of macrovascular complications in patients with type 2 diabetes mellitus: Review of cardiovascular safety and efficacy of newer diabetes medications

Lack of conclusive beneficial effects of strict glycemic control on macrovascular complications has been very frustrating for clinicians involved in care of patients with diabetes mellitus (DM). Highly publicized controversy surrounding cardiovascular (CV) safety of rosiglitazone resulted in major changes in United States Food and Drug Administration policy in 2008 regarding approval process of new antidiabetic medications, which has resulted in revolutionary data from several large CV outcome trials over the last few years. All drugs in glucagon-like peptide-1 receptor agonist (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT-2) inhibitor classes have shown to be CV safe with heterogeneous results on CV efficacy. Given twofold higher CV disease mortality in patients with DM than without DM, GLP-1 RAs and SGLT-2-inhibitors are important additions to clinician’s armamentarium and should be second line-therapy particularly in patients with T2DM and established atherosclerotic CV disease or high risks for CV disease. Abundance of data and heterogeneity in CV outcome trials results can make it difficult for clinicians, particularly primary care physicians, to stay updated with all the recent evidence. The scope of this comprehensive review will focus on all major CV outcome studies evaluating CV safety and efficacy of GLP-1 RAs and SGLT-2 inhibitors.