Type 2 Diabetes Mellitus Cardiovascular Disease Research Articles

Indication of Hyperhomocysteinemia in Type 2 Diabetes Mellitus Patients with Cardiovascular Complications

Introduction Cardiovascular disease (CVD) is one of the prominent causes of mortality in cases of chronic Type 2 diabetes mellitus (T2DM) patients and necessitates improving risk categorization. There are few available biomarkers that can assess preceding or current glycemic and cardiac status, but not prognosis. Serum homocysteine (Hcy) has been indicated and reported to be a likely biomarker that can detect cardiovascular complication in patients with T2DM. Methodology Present study details the comparative analysis of several biochemical and metabolic biomarkers including Hcy in T2DM patients with and without CVD complications. A total of eighty patients, n = 40 each in T2DM with CVD and T2DM without CVD, were included in the study. Patient’s preparation, blood sample collection and analyses of all biochemical, metabolic markers including Hcy were performed as per standard protocols. One way ANOVA was used for independent measures including Tukey HSD with level of significance at P< 0.05. Results Indication of hyperhomocysteinemia, was significantly apparent in patients with T2DM who have CVD, as compared to those with T2DM without CVD. All other biochemical and metabolic parameters manifested marked significant (P< 0.00001) elevations, which was more perceptible in T2DM CVD as compared to T2DM non CVD. Clinical relevance of high Hcy in blood in patients with T2DM CVD thus suggested being prominent risk factor for proceeding renal and cardiac complications.

Impact of type 2 diabetes mellitus on low-grade inflammation in patients with ST-elevated myocardial infarction

Chronic low-grade inflammation has emerged as a hallmark of type 2 diabetes mellitus (T2DM), contributing significantly to the pathogenesis of various cardiovascular diseases, notably ST-elevated myocardial infarction (STEMI). The intricate interplay between inflammation and cardiovascular health in the context of T2DM has been a subject of intensive research in recent years. In particular, the development of various markers of inflammation has provided valuable tools for better understanding the complex relationship between low-grade inflammation and cardiovascular disease in T2DM. Elevated levels of these markers have been consistently associated with increased cardiovascular risk in patients with T2DM, indicating their potential as prognostic indicators. The aim of the study was to investigate the potential association between type 2 diabetes mellitus and low-grade inflammation markers in patients with ST-elevated myocardial infarction through a comparative analysis of systemic immune-inflammation indices, fibronectin, and soluble suppression of tumorogenesis-2 (sST2) levels in ST-elevated myocardial infarction patients with and without type 2 diabetes mellitus. We enrolled 158 patients diagnosed with STEMI who were admitted to the Ivano-Frankivsk Regional Clinical Cardiological Center. The study population was divided into three groups: 1 – consisting of 45 patients with both STEMI and T2DM, and the 2 – consisting of 34 patients with STEMI only, T2DM only group – 69 patients, Control group – 10 healthy patients. In summary, the findings from the study provide compelling evidence to support the notion that patients who suffer from both STEM and T2DM exhibit a more robust inflammatory response and higher platelet count, compared to those with STEMI alone. These results suggest that the presence of T2DM may exacerbate the pro-inflammatory and pro-thrombotic state that is typically associated with STEMI, thereby emphasizing the critical need for early intervention to prevent or mitigate inflammation and platelet activation in this particular patient population. Type 2 diabetes mellitus patients with ST-segment elevation myocardial infarction show higher levels of inflammation markers and fibronectin, indicating greater low-grade inflammation. Elevated levels of soluble suppression of tumorigenicity 2 suggest myocardial remodeling. Targeting low-grade inflammation could be a potential therapy for STEMI in T2DM patients.

Optimizing statin therapy for primary prevention of cardiovascular disease in type 2 diabetes mellitus patients: Exploring dose, class, and intensity.

To investigate the impact of statin use on primary prevention of cardiovascular disease (CVD) in patients with type 2 diabetes mellitus (T2DM) in a dose-, class-, and use intensity-dependent manner. We used an inverse probability treatment-weighted Cox hazards model, with statin use status as a time-dependent variable. Our results showed that statin use was associated with a significant reduction in CVD risk with an adjusted hazard ratio of 0.39. Pitavastatin was found to have the lowest CVD risk among the different classes of statins, followed by rosuvastatin, pravastatin, atorvastatin, simvastatin, fluvastatin, and lovastatin. Our analysis also revealed that a higher cumulative defined daily dose per year of statin was associated with a lower CVD risk. Additionally, a higher intensity of daily statin dose was associated with a lower CVD risk in patients with T2DM. This study highlights the importance of statin use in reducing the risk of CVD in patients with T2DM, and the significance of dose, class, and intensity of statin use, in particular, pitavastatin class of statins was found to be the most effective in primary prevention of CVD in T2DM.

Low expression of lncRNA UCA1 assists the diagnosis of type 2 diabetes mellitus and predicts an increased risk of cardiovascular complications

ABSTRACT Type 2 diabetes mellitus (T2DM) is a leading global health concern. The study estimated the lncRNA UCA1 expression in peripheral blood of T2DM patients and its clinical value for diagnosing T2DM and predicting cardiovascular disease (CVD) in T2DM. A total of 80 T2DM patients (37 cases with T2DM complicated with CVD) were selected, with another 70 healthy people as controls. UCA1 expression was measured, and its diagnostic efficacy for T2DM was assessed. Median UCA1 level divided T2DM patients into UCA1 low expression group and UCA1 high expression group, and its correlation with clinical indicators of T2DM patients was analyzed. Relevance between UCA1 and SADN, YKL-40 or CTRP-3 in T2DM complicated with CVD patients, and independent correlation between UCA1 and CVD in T2DM were evaluated. UCA1 was downregulated in T2DM patients, associated with clinical indicators, and assisted the diagnosis of T2DM. UCA1 was positively-correlated with SADN and CTRP-3, and negatively interrelated with YKL-40. UCA1 low expression was independently linked with and predicted an enhanced risk of CVD in T2DM patients. Briefly, UCA1 low expression assists the diagnosis of T2DM and predicts an increased risk of CVD in T2DM patients.

Comorbidity of Type 2 Diabetes Mellitus and Depression: Clinical Evidence and Rationale for the Exacerbation of Cardiovascular Disease.

Depression is a common comorbidity of type 2 diabetes mellitus (T2DM). T2DM with comorbid depression increases the risk of cardiovascular events and death. Depression and T2DM and its macrovascular complications exhibited a two-way relationship. Regarding treatment, antidepressants can affect the development of T2DM and cardiovascular events, and hypoglycemic drugs can also affect the development of depression and cardiovascular events. The combination of these two types of medications may increase the risk of the first myocardial infarction. Herein, we review the latest research progress in the exacerbation of cardiovascular disease due to T2DM with comorbid depression and provide a rationale and an outlook for the prevention and treatment of cardiovascular disease in T2DM with comorbid depression.

Cardiovascular Effects of Incretin-Based Therapies: Integrating Mechanisms With Cardiovascular Outcome Trials.

As the worldwide prevalence of diabetes and obesity continues to rise, so does the risk of debilitating cardiovascular complications. Given the significant association between diabetes and cardiovascular risk, the actions of glucose-lowering therapies within the cardiovascular system must be clearly defined. Incretin hormones, including GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic polypeptide), are gut hormones secreted in response to nutrient intake that maintain glycemic control by regulating insulin and glucagon release. GLP-1 receptor agonists (GLP-1Ras) and dipeptidyl peptidase 4 inhibitors (DPP-4is) represent two drug classes used for the treatment of type 2 diabetes mellitus (T2DM) that improve glucose regulation through stimulating the actions of gut-derived incretin hormones or inhibiting their degradation, respectively. Despite both classes acting to potentiate the incretin response, the potential cardioprotective benefits afforded by GLP-1Ras have not been recapitulated in cardiovascular outcome trials (CVOTs) evaluating DPP-4is. This review provides insights through discussion of clinical and preclinical studies to illuminate the physiological mechanisms that may underlie and reconcile observations from GLP-1Ra and DPP-4i CVOTs. Furthermore, critical knowledge gaps and areas for further investigation will be emphasized to guide future studies and, ultimately, facilitate improved clinical management of cardiovascular disease in T2DM.

1129-P: The Genetic Architecture of Cardiovascular Disease in Individuals with Type 2 Diabetes

Background: Type 2 diabetes mellitus (T2DM) is a known risk factor for cardiovascular disease including coronary heart disease (CHD), stroke, and peripheral vascular disease (PVD). However, the genetic underpinnings of cardiovascular disease in those with T2DM is not well understood. Methods: Using 15 studies from dbGaP and the UK Biobank, we conducted the largest to date genome-wide association studies (GWAS) for CHD, stroke and PVD in up to 61,880 individuals with T2DM including 47,140 of European, 8,891 of African, 2,622 of Hispanic, 2,120 of South Asian and 1,107 of East Asian ancestry. GWAS were combined via ancestry-specific and transethnic meta-analyses with fixed-effects. Additional transethnic analysis with MR-MEGA was conducted to account for heterogeneity in allelic effects correlated with ancestry. Results: We replicated previously reported CHD associated loci at genome-wide significance (GW, p≤5×10-8) including 9p21, LPA, and PSRC1. Combining our results with those of prior CHD GWAS in T2DM revealed additional GW significant signals in known CHD loci: PHACTR1, ADAMTS7, HHIPL1, and LPL. European ancestry specific analysis confirmed prior GW significant associations between LPA and PHACTR1 loci and PVD. MR-MEGA analysis of PVD identified novel GW significant loci in CNST and AVPI1. We found a significant genetic correlation of 0.74 (SE= .27) between CHD and PVD. Transethnic analysis of stroke GWAS yielded no GW significant loci. However, African ancestry specific analysis yielded two novel GW signals in the NKAIN2 and BRF1 loci. A significant association between interleukin-6 signaling and stroke was identified using pathway analysis. Conclusions: Ancestry-specific and transethnic analysis of cardiovascular disease in T2DM confirmed prior CHD GWAS findings and revealed novel associations with PVD and stroke that warrant further investigation. Disclosure E. L. Richard: None. S. Cao: None. A. Shadyab: None. R. Salem: None. Funding National Institutes of Health

Association of BMI with cardiovascular disease incidence and mortality in patients with type 2 diabetes mellitus: A systematic review and dose–response meta-analysis of cohort studies

AimsThe relation of body mass index (BMI) with cardiovascular disease (CVD) and mortality has been extensively investigated in the general population but is less clear in individuals with type 2 diabetes mellitus (T2DM). We performed a meta-analysis of cohort studies to quantitatively evaluate the association of BMI with CVD incidence and mortality in patients with T2DM. Data synthesisPubMed and Embase databases were searched for relevant cohort articles published up to June 8, 2020. Restricted cubic splines were used to evaluate the potential linear or non-linear dose–response associations. We identified 17 articles (21 studies) with 1,349,075 participants and 57,725 cases (49,354 CVD incidence and 8371 CVD mortality) in the meta-analysis. We found a linear association between BMI and risk of CVD incidence (Pnon-linearity = 0.182); the pooled RR for CVD incidence was 1.12 (95% CI, 1.04–1.20) with a 5-unit increase in BMI. We found an overall nonlinear relationship between BMI and CVD mortality (Pnon-linearity < 0.001). The lowest risk was at BMI about 28.4 kg/m2, with increased mortality risk for higher BMI values; the RR with a 5-unit increase in BMI was 0.87 (95% CI, 0.79–0.96) and 1.11 (95% CI, 1.04–1.18) for BMI ≤28.4 kg/m2 and BMI >28.4 kg/m2, respectively. ConclusionsIn individuals with T2DM, BMI may have a positive linear association with risk of CVD incidence but a nonlinear association with CVD mortality. Our results can provide evidence for weight control and lifestyle intervention for preventing and managing cardiovascular disease in T2DM.

Sodium-glucose co-transporter-2 inhibitors in patients with type 2 diabetes mellitus without established cardiovascular disease: Do they have a role in primary prevention?

Most guidelines and cardiovascular outcome trials (CVOTs) focus on secondary prevention of cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM). Patients with T2DM without established CVD (eCVD) also form a critical cohort, for whom primary prevention with timely pharmacological and non-pharmacological interventions can effectively prevent or delay the onset of CVD. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have demonstrated a promising role for primary prevention of CVD in CVOTs and real-world studies. The 2019 American College of Cardiology/American Heart Association guidelines on primary prevention of CVD recommend SGLT2i as one of the add-on treatment options to metformin for adults with T2DM and glycated hemoglobin >7% who have cardiovascular (CV) risk factors. The outcomes with maximal response to SGLT2i use in primary prevention are hospitalization for heart failure and chronic kidney disease. The cardiorenal benefits with SGLT2i are attributed to pleiotropic effects on CV risk factors, and interference with glucose and sodium handling in kidneys, independent of their glycemic benefits. Results therefore support a role for SGLT2i not only in patients with T2DM and eCVD but also in patients with T2DM without eCVD. This review examines the evidence for potential role of SGLT2i for primary prevention of CVD in T2DM.

Randomised, cOntrolled Multicentre trial of 26 weeks subcutaneous liraglutide (a glucagon-like peptide-1 receptor Agonist), with or without contiNuous positive airway pressure (CPAP), in patients with type 2 diabetes mellitus (T2DM) and obstructive sleep apnoEa (OSA) (ROMANCE): study protocol assessing the effects of weight loss on the apnea–hypnoea index (AHI)

IntroductionObstructive sleep apnoea (OSA) and type 2 diabetes mellitus (T2DM) often occur concurrently, and untreated OSA may potentially amplify the high risk of cardiovascular disease in T2DM. Compliance with continuous...

The Association Between Acylcarnitine Metabolites and Cardiovascular Disease in Chinese Patients With Type 2 Diabetes Mellitus.

Objective: The association between acylcarnitine metabolites and cardiovascular disease (CVD) in type 2 diabetes mellitus (T2DM) remains uncertain. This study aimed to investigate associations between acylcarnitines and CVD in Chinese patients with T2DM.Methods: A cross-sectional study was conducted from May 2015 to August 2016. Medical records of 741 patients with T2DM were retrieved from the main electronic database of Liaoning Medical University First Affiliated Hospital. CVD was defined as having either coronary artery disease (CAD) or heart failure (HF) or stroke. Mass Spectrometry was utilized to measure levels of 25 acylcarnitine metabolites in fasting plasma. Factor analysis was used to reduce the dimensions and extracted factors of the 25 acylcarnitine metabolites. Multivariable binary logistic regression was used to obtain odds ratios (OR) of the factors extracted from the 25 acylcarnitine metabolites and their 95% confidence intervals (CI) for CVD.Results: Of the 741 patients with T2DM, 288 had CVD. Five factors were extracted from the 25 acylcarnitines and they accounted for 65.9% of the total variance. Factor 1 consisted of acetylcarnitine, butyrylcarnitine, hydroxylbutyrylcarnitine, glutarylcarnitine, hexanoylcarnitine, octanoylcarnitine, and tetradecanoyldiacylcarnitine. Factor 2 consisted of decanoylcarnitine, lauroylcarnitine, myristoylcarnitine, 3-hydroxyl-tetradecanoylcarnitine, tetradecenoylcarnitine, and 3-hydroxypalmitoylcarnitine. After adjusting for potential confounders, increased factor 1 and 2 were associated with increased risks of CVD in T2DM (OR of factor 1: 1.45, 95% CI: 1.03–2.03; OR of factor 2: 1.23, 95% CI: 1.02–1.50).Conclusions: Elevated plasma levels of some acylcarnitine metabolites, i.e., those extracted into factor 1 and 2, were associated with CVD risk in T2DM.

Pharmacological Management of Cardiac Disease in Patients with Type 2 Diabetes: Insights into Clinical Practice.

Type 2 Diabetes Mellitus (T2DM) has emerged as a growing pandemic. Cardiovascular disease (CVD) constitutes another major health problem, with coronary heart disease being the leading cause of cardiovascular death. Patients with T2DM require a multilevel therapeutic approach, both for primary and secondary prevention of CVD. To present and summarize the most recent, highest level evidence retrieved from literature, relevant to the pharmaceutical management of CVD in T2DM. We conducted a comprehensive search of the literature on MEDLINE from its inception till today, primarily for relevant systematic reviews, meta-analyses and randomized controlled trials. There is a trend towards more intensified therapeutic interventions in T2DM, concerning glycemic, lipid and blood pressure control. New drugs, such as sodium-glucose co-transporter 2 (SGLT-2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs) and proprotein convertase subtilisin/ kexin type 9 (PCSK9) inhibitors might evolve as key players in the management of diabetes and its complications within the next years. Classic drugs, such as those targeting the renin-angiotensinaldosterone system, statins and aspirin remain first-line treatment options, both for primary and secondary prevention of CVD. Lifestyle interventions should always be integrated into a complete therapeutic strategy in diabetic patients. Novel drugs, such as finerenone and LCZ696 have provided significant results in cardiovascular outcome studies; however, their role in T2DM has to be further elucidated. Pharmaceutical approach of CVD in T2DM is multilevel and complex. Drug classes featuring pleiotropic effects may boost our armamentarium in the fight against CVD.

Interaction between endothelial nitric oxide synthase rs1799983, cholesteryl ester-transfer protein rs708272 and angiopoietin-like protein 8 rs2278426 gene variants highly elevates the risk of type 2 diabetes mellitus and cardiovascular disease

BackgroundThe aim of the present study was to examine the association of angiopoietin-like proteins-8 (ANGPTL8) rs2278426, cholesteryl ester-transfer protein (CETP) rs708272 and endothelial nitric oxide synthase (NOS3) rs1799983 variants with type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD), and to investigate the effect of the potential interaction between these variants on disease risk.MethodsOur study included 272 subjects classified into 68 patients with T2DM, 68 patients with T2DM complicated with CVD and 136 control subjects. ANGPTL8 c194C>T, CETP Taq1B and NOS3 G894T polymorphisms were genotyped using TaqMan® SNP Genotyping Assay.ResultsThe presence of NOS3, ANGPTL8, and homozygous CETP B1 variants were associated with increased risk of T2DM by 3.07-, 2.33- and 1.75-fold, respectively. NOS3 variant was associated with 3.08-fold increased risk of CVD (95% CI 1.70–5.60), while ANGPTL8 C allele was associated with 2.8-fold increased risk of CVD in T2DM patients (95% CI 1.13–6.97). Concomitant presence of both, CETP B1 and NOS3 T allele, associated with increased risk of T2DM, CVD and CVD in T2DM by 8.36-, 6.33- and 7.87-fold, respectively, while concomitant presence of ANGPTL8 variant with either CETP B1 or NOS3 T allele was not associated with increased risk of T2DM or CVD. However, concomitant presence of the three variants together elevated the risk of T2DM by 13.22-fold (p = 0.004), CVD risk by 8.86-fold (p = 0.03) and highly elevated the risk of CVD in T2DM patients by 13.8-fold (p = 0.008).ConclusionsConcomitant presence of CETP B1, NOS3 T and ANGPTL8 T alleles augments the risk of CVD and T2DM. Further studies to clarify the mechanism of gene–gene interaction in the pathogenesis of CVD and T2DM are needed.

Assessment of gender-related differences in vitamin D levels and cardiovascular risk factors in Saudi patients with type 2 diabetes mellitus.

Diabetes is a major risk factor for cardiovascular disease (CVD) including stroke, coronary heart disease, and peripheral artery disease. It remains a leading cause of mortality throughout the world, affecting both women and men. This investigation was aimed to study gender based differences in cardiovascular risk factors of adult population with type-2 diabetes mellitus (T2DM) and to check the correlation between serum HbA1C, lipid profile and serum vitamin D levels, in T2DM patients of Riyadh, Saudi Arabia. This hospital-based cross-sectional study involving subjects was divided into two gender based groups; normal male (800), diabetic male (800) and normal female (800) and T2DM females (800). Blood samples were analyzed for fasting glucose (FBG), HbA1c, total cholesterol (TC), triglycerides (Tg), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and serum levels of 25(OH)-vitamin D in all groups. All the glycemic control parameters and lipid profile parameters were found to be significantly different in diabetic vs non-diabetic group (p < 0.001) in both genders. The results also show that vitamin D concentration decreased significantly (p < 0.001) in diabetic patients than the healthy individuals in both the genders. Vitamin-D and HbA1C were negatively correlated in both males and females in T2DM patients and significant at P < 0.05. Our study reveals that dyslipidemia remains one of the major risk factors of CVD in T2DM. In addition to dyslipidemia, decreased levels of vitamin-D associated with increased HbA1C alarms the early diagnosis of Type 2 Diabetes.

Abstract 14: The Anti-atherosclerosis ABCA1 Agonist CS6253 Confer Glucose Control by Improved Pancreas Beta-cell Insulin Secretion and Enhanced Peripheral Insulin Utility

Background: Type 2 Diabetes Mellitus (T2DM) is associated with high cardiovascular disease (CVD) risk. Addressing the underlying atherogenesis and diabetes causing CVD in T2DM is important. CS6253 is an ABCA1 agonist peptide derived from the C-terminal of apoE that has shown macrophage specific reverse cholesterol transport, anti-atherosclerosis and anti-diabetic properties. Further studies were carried out to characterize metabolic effects. Methods: CS6253 was incubated with a) INS-1 823/13 cells to assess effects on insulin secretion and b) with L6-Glut4myc rat myoblasts to assess glucose uptake properties. Diet Induced Obesity (DIO) mice, i.e. C57BL/6 mice that had been fed 60% high-fat diet for 6 weeks, were treated with CS6253 and Glucose Tolerance Tests (GTT) performed after overnights fasting administering glucose 1g/kg ip. Results: CS6253 1mg/mL incubated for 2 hours under standard conditions with 3mM glucose showed a 3-fold increase in insulin secretion compared to control, i.e. 232(32) vs. 79(7) ng/M cells, p&lt;0.001. 3 H-glucose uptake by CS6253 peptide in L6-Glut4myc rat myoblasts increased insulin’s glucose uptake capacity from 3800 to 4619 DPM/well, p&lt;0.001 . CS6253 alone had no effect on 3 H-glucose uptake compared to control. DIO mice were treated with CS6253 30mg/kg sc alternate days or PBS control for 16 weeks. GTTs were performed after 2, 6 and 15 weeks treatment showing 39%, 45% and 57% reductions in the glucose-AUC compared to control, respectively, p&lt;0.01 for all time points. Insulin response to GTT after 5 weeks treatment showed a strong improvement of the insulin-curve by CS6253, p&lt;0.05 vs. placebo. CS6253 treated DIO mice showed a non-significant body weight decrease and a 17% reduction in liver weight, 5.28g vs. 4.36g, p&lt;0.01. Discussion: CS6253 shows potent, sustained and increased anti-diabetic actions over the 16 weeks treatment period in DIO mice. In vivo and in vitro studies show improved pancreas β-cell function with increased glucose-mediated insulin secretion and also insulin sensitizing properties. CS6253’s combined anti-diabetic and anti-atherosclerosis properties suggest utility in the treatment of CVD and T2DM.

Mechanisms of Cardiovascular Injury in Type 2 Diabetes and Potential Effects of Dipeptidyl Peptidase-4 Inhibition.

Cardiovascular (CV) disease is the major cause of mortality and morbidity in patients with type 2 diabetes mellitus (T2DM). The pathogenesis of CV disease in T2DM is complex and multifactorial and involves direct and indirect injury to the vasculature and heart. The impact of intensive glucose-lowering therapy with antihyperglycemic agents on CV outcomes is not clear, and questions remain as to which glucose-lowering agents may be beneficial to CV health in patients with T2DM. This review discusses findings regarding the known mechanisms of CV injury in T2DM and current knowledge regarding the potential cardioprotective effects of dipeptidyl peptidase-4 (DPP-4) inhibitors. Dipeptidyl peptidase-4 inhibitors are relatively new antihyperglycemic agents. Their main mechanism of action is to inhibit the degradation of the incretin hormones glucagon-like peptide-1 and glucose-dependent insulinotropic peptide by DPP-4. By increasing levels of glucagon-like peptide-1, glucose-dependent insulin secretion is enhanced, glucagon secretion is suppressed, and the rate of gastric emptying is decreased. Dipeptidyl peptidase-4 also degrades other substances that are important in the regulation of CV function and inflammation. Animal studies, small observational studies in humans, and analyses of clinical trial data suggest that DPP-4 inhibitors may have beneficial CV effects. Recent prospectively designed CV outcomes trials with saxagliptin and alogliptin in patients with T2DM and high CV risk presented evidence that these DPP-4 inhibitors neither increased nor decreased adverse CV outcomes in this select patient population. Dipeptidyl peptidase-4 inhibitors are promising therapies for the treatment of T2DM. Able to improve glycemic control without the risk of weight gain or hypoglycemia, they provide a safe alternative to sulfonylureas and are an effective adjunct to metformin. To date, this class of drugs seems to be at least neutral in terms of CV effects. Time will tell if these findings translate into a benefit for our patients.

Lp-PLA2, a Novel Potential Biomarker Predicting Cardiovascular Disease in Type 2 Diabetes Mellitus

Cardiovascular disease (CVD) is the fatal complication of diabetes mellitus and it is a large economic burden of the world. Although there are a few biomarkers in predicting the cardiovascular disease, the disease is still far from being diagnosed and evaluated precisely in type 2 diabetes mellitus (T2DM) patients. Lp-PLA2 takes part in several links of the pathological mechanism in the diabetic cardiovascular disease. Researches have implied that the Lp-PLA2 has positive association with CVD severity in T2DM. Lp-PLA2 may be a novel biomarker diagnosing and evaluating CVD in T2DM.

Impact of glucose-lowering drugs on cardiovascular disease in type 2 diabetes

Type 2 diabetes mellitus (T2DM) is characterized by multiple pathophysiologic abnormalities. With time, multiple glucose-lowering medications are commonly required to reduce and maintain plasma glucose concentrations within the normal range. Type 2 diabetes mellitus individuals also are at a very high risk for microvascular complications and the incidence of heart attack and stroke is increased two- to three-fold compared with non-diabetic individuals. Therefore, when selecting medications to normalize glucose levels in T2DM patients, it is important that the agent not aggravate, and ideally even improve, cardiovascular risk factors (CVRFs) and reduce cardiovascular morbidity and mortality. In this review, we examine the effect of oral (metformin, sulfonylureas, meglitinides, thiazolidinediones, DPP4 inhibitors, SGLT2 inhibitors, and α-glucosidase inhibitors) and injectable (glucagon-like peptide-1 receptor agonists and insulin) glucose-lowering drugs on established CVRFs and long-term studies of cardiovascular outcomes. Firm evidence that in T2DM cardiovascular disease can be reversed or prevented by improving glycaemic control is still incomplete and must await large, long-term clinical trials in patients at low risk using modern treatment strategies, i.e., drug combinations designed to maximize HbA1c reduction while minimizing hypoglycaemia and excessive weight gain.

Profile of liver enzymes in non-alcoholic fatty liver disease in patients with impaired glucose tolerance and newly detected untreated type 2 diabetes.

Context:The perception of non-alcoholic fatty liver disease (NAFLD) as an uncommon and benign condition is rapidly changing. Approximately, 70% type 2 diabetes mellitus (T2DM) patients have a fatty liver, which may follow an aggressive course with necroinflammation and fibrosis.Aims:To assess the profile of liver enzymes in subjects with impaired glucose tolerance (IGT), new onset treatment naive T2DM and normal glucose tolerance (NGT) with and without NAFLD.Settings and Design:Cross-sectional clinic-based study.Subjects and Methods:152 IGT and 158 recently detected T2DM subjects aged between 30 and 69 years, along with 160 age and gender matched controls with NGT. An ultrasonography scan of the upper abdomen was done in all patients in order to examine presence of fatty liver. Anthropometry, lipid profile, liver enzymes were also analyzed in all patients.Statistical Analysis Used:Unpaired t-test, Chi-square/Fisher Exact test (for categorical variables), Pearson/Spearmen correlation test to find significant difference, association and correlation between two or more groups respectively.Results:NAFLD was significantly associated with higher alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) but not ALP levels in IGT and T2DM patients. ALT, GGT significant correlated with waist circumference, body mass index, fasting insulin, homeostatic model assessment- insulin resistance, fasting blood glucose, high density lipoprotein cholesterol, triglyceride. 57% of NAFLD patients had normal ALT between 25 and 40 U/L, 53% of NAFLD subjects had normal GGT between 15 and 30 U/L. ALT <25 U/L and GGT <15 U/L had highest negative predictivity whereas ALT >40 U/L and GGT > 30 U/L had highest positive predictivity for presence of NAFLD in our study sample.Conclusions:Mild elevations of liver enzymes in the upper normal range are associated with features of metabolic syndrome and NAFLD even in IGT and recently detected T2DM patients. Novel cut-offs for liver enzymes are warranted in order to prevent unnecessary diagnostic work-ups and early detection of NAFLD to reduce the risk of cirrhosis, hepatocellular carcinoma and classical cardiovascular disease in T2DM and IGT patients.

Potential Impact of Dipeptidyl Peptidase-4 Inhibitors on Cardiovascular Pathophysiology in Type 2 Diabetes Mellitus

Cardiovascular (CV) disease remains the major cause of mortality and morbidity in patients with type 2 diabetes mellitus (T2DM). The pathogenesis of CV disease in T2DM is complex and multifactorial, and includes abnormalities in endothelial cells, vascular smooth muscle cells, myocardium, platelets, and the coagulation cascade. Dipeptidyl peptidase-4 (DPP-4) inhibitors are a newer class of agents that act by potentiating the action of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide. This review summarizes CV disease pathophysiology in T2DM and the potential effect of DPP-4 inhibitors on CV risk in patients with T2DM. Preclinical and small observational studies and post hoc analyses of clinical trial data suggest that DPP-4 inhibitors may have beneficial CV effects. Some effects of DPP-4 inhibitors are GLP-1 dependent, whereas others may be due to GLP-1–independent actions of DPP-4 inhibitors. Analyses of major adverse CV events occurring during clinical development of DPP-4 inhibitors found no increased risk of CV events or mortality and even a potential reduction in CV events. Two large CV outcome trials have been completed and report that saxagliptin and alogliptin did not increase or decrease adverse CV outcomes in patients with T2DM and CV disease or at high risk for adverse CV events. More patients in the saxagliptin group than in the placebo group were hospitalized for heart failure, and there was a similar numerically increased risk of hospitalization for heart failure with alogliptin; however, the risk was not significantly greater compared with placebo. Dipeptidyl peptidase-4 inhibitors may affect some of the pathologic processes involved in the increased CV risk inherent in T2DM.