Mechanisms underlying heart failure in type 2 diabetes mellitus

2019 ◽  
pp. 37-39
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Experimental Studies ◽  
Vascular Complications ◽  
Molecular Alterations ◽  
Increased Risk ◽  
Cardioprotective Effects ◽  
Underlying Mechanisms ◽  
Cardio Vascular

The prevalence of heart failure is markedly increased in individuals with diabetes mellitus. Numerous observational studies suggest that this increased risk for heart failure can be attributed to exacerbated vascular complications and the presence of increased risk factors in diabetic subjects. In addition, experimental studies revealed the presence of a number of distinct molecular alterations in the myocardium that occur independently of vascular disease and hypertension. Many of these molecular alterations are similarly observed in failing hearts of nondiabetic patients and have thus been proposed to contribute to the increased risk for heart failure in diabetes. The interest in understanding the underlying mechanisms of impaired cardio- vascular outcomes in diabetic individuals has much increased since the demonstration of cardioprotective effects of SGLT-2 inhibitors and GLP-1 receptor agonists in recent clinical trials. The current review therefore summarizes the distinct mechanisms that have been proposed to increase the risk for heart failure in diabetes mellitus.

scholarly journals Plasminogen activator inhibitor-1 gene polymorphism as a risk factor for vascular complications in type 2 diabetes mellitus

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Fatma A. Khalaf ◽  
Hatem R. Ibrahim ◽  
Hanan M. Bedair ◽  
Maha M. Allam ◽  
Amr A. Elshormilisy ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gene Polymorphism ◽  
Vascular Complications ◽  
Plasminogen Activator Inhibitor ◽  
Diabetic Patients ◽  
Plasminogen Activator Inhibitor 1 ◽  
Increased Risk ◽  
Activator Inhibitor ◽  
Pai 1

Abstract Background Diabetes mellitus (DM) can lead to microvascular and macrovascular damages through hyperglycemia that is the main cause of diabetic complications. Other factors such as hypertension, obesity, and hyperlipidemia may worsen or accelerate the others. Several studies have revealed definitive genetic predispositions to the development of type 2 diabetes mellitus (T2DM) and development of vascular complications. This study aimed to address the association between plasminogen activator inhibitor-1 (PAI-1) gene polymorphism and T2DM, and if this gene polymorphism may have a possible role in the development of vascular complications in T2DM. This study is a case control; it included 200 patients with T2DM, 117 patients had no vascular complications, and 83 had previous vascular complications (VCs). One hundred eighty volunteer blood donors were selected as a healthy control group. All patients and controls were subjected to clinical examination, and laboratory investigations included lipid profile, fasting and 2 h blood glucose, complete blood cell count, d-dimer, PAI-1, thrombin activatable fibrinolysis inhibitor (TAFI), and detection of PAI-1 gene polymorphism by real-time polymerase chain reaction (PCR). Results The most prevalent genotype of PAI-1 gene polymorphism in all studied groups, including controls, was 4G/5G with the highest allele frequency as 4G. The 4G/5G and 4G/4G genotypes were associated with increased risk of DM development as compared to 5G/5G genotype. The 4G/5G and 4G/4G genotypes also had a highly significant increased risk of VCs among diabetic patients, as compared to 5G/5G. The 4G allele also was highly associated with DM with VCs. The d-dimer TAFI, PAI-1 showed the highest levels in 4G/5G genotype followed by 4G/4G genotype. The lowest level was expressed in 5G/5G genotype in diabetic patients with and without VCs. The univariable analysis showed that genotypes 4G/5G and 4G/4G were potentially risk factors for development of VCs with T2DM patients. Conclusion This study concludes that the PAI-1 4G/5G polymorphism may be associated with T2DM and may be considered as a risk factor for development of thrombotic events. It may also help in selection and dosing of patients being treated with anticoagulant and fibrinolytic agents. Further large-scale studies are recommended to assess the possible role of environmental factors and gene interactions in the development of T2DM vascular risks.

scholarly journals Association between Markers of Fibrosis and Heart Failure Incidence in Patients with Type 2 Diabetes Mellitus

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Denis A. Lebedev ◽  
Elena A. Lyasnikova ◽  
Elena Yu. Vasilyeva ◽  
Nikolai P. Likhonosov ◽  
Maria Yu. Sitnikova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Type I ◽  
Procollagen Type ◽  
Sodium Glucose Cotransporter ◽  
Increased Risk

Type 2 diabetes mellitus (T2DM) and chronic heart failure (HF) have close association, and several biomarkers have been studied to better understand this association and improve prediction of HF in T2DM. Furthermore, in recent clinical trials, sodium glucose cotransporter 2 inhibitors (SGLT2i), glucose-lowering drugs, improved HF outcomes. The objective of the present study was to evaluate association between circulating biomarkers of fibrosis and incidence of HF with preserved ejection fraction (HFpEF) in patients with T2DM receiving sodium glucose cotransporter 2 inhibitors (SGLT2i). Materials and Methods. At baseline, transthoracic echocardiography and laboratory assessment of N-terminal fragment of the brain natriuretic peptide (Nt-proBNP), soluble suppression of tumorigenesis-2 (sST2), galectin-3 (Gal-3), C-terminal propeptide of procollagen type I (PICP), N-terminal propeptide of procollagen type III (PIIINP), matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix proteinase-1 (TIMP-1) were done. After 3 years of follow-up, information about HF events (hospitalization for HF, established HF in outpatient department by a cardiologist) was obtained. Results. Seventy-two patients were included in the study. The mean age was 57 (49.7; 63.2) years; 44% were female. Most patients had T2DM for more than 4 years. All patients were overweight or had obesity, and 93% patients had arterial hypertension (AH). After 3 years of follow-up, HFpEF was established in 21% patients. Patients were divided into two groups according to the presence of HFpEF, and baseline characteristics were compared. Patients with HF were older and had longer diabetes and AH duration and higher Nt-proBNP, Gal-3, PIIINP, and PICP levels at baseline than patients without HF (all p < 0.05 ). Gal − 3 > 10  ng/ml ( OR = 2.25 ; 95% CI, 1.88–5.66; p = 0.01 ) and NT − pro − BNP > 80  pg/ml ( OR = 2.64 ; 95% CI, 1.56–4.44; p = 0.001 ) were associated with increased risk of HF incidence. Age > 60 years, diabetes duration > 10 years, and presence of abdominal obesity were independent predictors of HFpEF as well. Conclusions. T2DM patients treated with SLGT2i, who developed HFpEF after 3 years of follow-up, had higher PICP, PIIINP, Gal-3, and NT-proBNP serum concentrations at baseline, and Gal-3 level was an independent predictor of HFpEF.

scholarly journals Economic evaluation of type 2 diabetes mellitus burden and its main cardiovascular complications in the Russian Federation

2016 ◽  
Vol 19 (6) ◽  
pp. 518-527 ◽  
Author(s):  
Ivan I. Dedov ◽  
Anna V. Koncevaya ◽  
Marina V. Shestakova ◽  
Yuriy B. Belousov ◽  
Julia A. Balanova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Russian Federation ◽  
Complex Analysis ◽  
Vascular Complications ◽  
Cardiovascular Complications ◽  
Permanent Disability ◽  
Clinical Investigations ◽  
The Russian Federation ◽  
Cardio Vascular

Background. Diabetes Mellitus Type 2 (DMT2) is a complex medical and social problem in the world and in the Russian Federation also due to prevalence and probability of cardio-vascular complications (CVC).Aim. Economic burden evaluation of DMT2 in the Russian Federation.Methods. Complex analysis of expenditures (direct and non-direct costs) based on epidemiological, pharmacoeconomics and clinical investigations, population and medical statistics data.Results. Calculated expenditures for DMT2 are 569 bln RUR per year, that is correspond to 1% of the Russian GDP, and 34,7% of that are expenditures for main CVC (ischemic heart disease, cardiac infarction, stroke). Main part of expenses are non-medical (losses GDP) due to temporary and permanent disability, untimely mortality – 426,7 bln RUR per year. Expenditures in estimated group of patients with non-diagnosed DMT2 but with already having CVC were at least 107 bln per year (18,8% from total cost). Relationship between cost of DMT2 and degree of it’s control was found in the Russian conditions. Estimated cost for compensated patient (HbA1c6,5%) per year was 88 982 RUR, in the same time cost of non-control patient (HbA1c9,5%) was in 2,8 times higher due to more often main CVC in this group.Conclusion. DMT2 diagnosis improvement as well as effective treatment of early stages of illness can decrease probability of CVC and social economic expenditures. 

scholarly journals GRB10 rs1800504 Polymorphism Is Associated With the Risk of Coronary Heart Disease in Patients With Type 2 Diabetes Mellitus

2021 ◽  
Vol 8 ◽  
Author(s):  
Yang Yang ◽  
Wentao Qiu ◽  
Qian Meng ◽  
Mouze Liu ◽  
Weijie Lin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Coronary Heart Disease ◽  
Type 2 Diabetes Mellitus ◽  
Heart Disease ◽  
Vascular Complications ◽  
Nucleotide Polymorphisms ◽  
Diabetic Vascular Complications ◽  
Increased Risk

Diabetic vascular complications are one of the main causes of death and disability. Previous studies have reported that genetic variation is associated with diabetic vascular complications. In this study, we aimed to investigate the association between GRB10 polymorphisms and susceptibility to type 2 diabetes mellitus (T2DM) vascular complications. Eight single nucleotide polymorphisms (SNPs) in the GRB10 gene were genotyped by MassARRAY system and 934 patients with type 2 diabetes mellitus (T2DM) were included for investigation. We found that GRB10 rs1800504 CC+CT genotypes were significantly associated with increased risk of coronary heart disease (CHD) compared with TT genotype (OR = 2.24; 95%CI: 1.36–3.70, p = 0.002). Consistently, levels of cholesterol (CHOL) (CC+CT vs. TT, 4.44 ± 1.25 vs. 4.10 ± 1.00 mmol/L; p = 0.009) and low density lipoprotein cholesterin (LDL-CH) (CC+CT vs. TT, 2.81 ± 1.07 vs. 2.53 ± 0.82 mmol/L; p = 0.01) in T2DM patients with TT genotype were significant lower than those of CC+CT genotypes. We further validated in MIHA cell that the total cholesterol (TC) level in GRB10-Mut was significantly reduced compared with GRB10-WT; p = 0.0005. Likewise, the reversed palmitic acid (PA) induced lipid droplet formation in GRB10-Mut was more effective than in GRB10-WT. These results suggest that rs1800504 of GRB10 variant may be associated with the blood lipids and then may also related to the risk of CHD in patients with T2DM.

scholarly journals Vitamin D Deficiency in Patients with Type 2 Diabetes Mellitus Leads to Vascular Complications

2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Salimah Navaz Gangji
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Vitamin D ◽  
Type 2 Diabetes Mellitus ◽  
Vascular Complications ◽  
Vitamin D Supplementation ◽  
Systemic Complications ◽  
Organ Systems ◽  
Increased Risk

The presence of hyperglycemia in individuals with Type 2 Diabetes Mellitus (T2DM) is associated with systemic complications within multiple organ systems. Specifically, patients with T2DM have an increased risk of developing vascular endothelial damage. Interestingly, patients with T2DM are often found to be deficient in vitamin D, a fat-soluble vitamin that not only plays a role in bone growth and gastrointestinal nutrient absorption, but insulin resistance as well. Thus, the purpose of this review is to summarize the literature that associates vitamin D deficiencies with vascular complications in both human and animal models with T2DM. This review will also summarize developments in genetic testing for VDR mutations and their potential role in diabetes progression, as well as the effects of vitamin D supplementation in patients with T2DM. Since T2DM is an increasingly prevalent disease, it is important to continue evaluating current research that investigates not only genetic causal factors for the disease, but also preventative options (such as vitamin D supplementation) that could potentially be used alongside pharmacological treatments.

scholarly journals Evaluation of the oxidative stress–related genes ALOX5, ALOX5AP, GPX1, GPX3 and MPO for contribution to the risk of type 2 diabetes mellitus in the Han Chinese population

2018 ◽  
Vol 15 (4) ◽  
pp. 336-339 ◽  
Author(s):  
Ding Liu ◽  
Lei Liu ◽  
Zhongyang Hu ◽  
Zhi Song ◽  
Yaqin Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Vascular Complications ◽  
Chinese Han ◽  
Carotid Plaques ◽  
Increased Risk ◽  
Stress Related Genes

Aim: Type 2 diabetes mellitus is a polygenic metabolic disorder resulting from oxidative stress, the root cause of insulin resistance, β-cell dysfunction and impaired glucose tolerance. The aim of this study was to investigate the role of oxidative stress–related genes ALOX5, ALOX5AP, GPX1, GPX3 and MPO in type 2 diabetes mellitus susceptibility in the Chinese Han population. Methods: A total of 396 type 2 diabetes mellitus patients and 678 controls were recruited. The ALOX5 rs10900213, ALOX5AP rs4293222, GPX1 rs1050450, GPX3 rs3828599 and MPO rs2107545 gene polymorphisms were genotyped. Results: We found one single-nucleotide polymorphism in the MPO gene was associated with type 2 diabetes mellitus susceptibility [rs2107545: odds ratio = 1.563 (1.166–2.096); p = 0.003], after adjusting for covariates. Furthermore, we also considered the likely complexity of effects of genetic and conventional risk factors in type 2 diabetes mellitus–related vascular complications, such as carotid plaques. Our analysis revealed that the GPX1 rs1050450 and MPO rs2107545 were significantly associated with increased risk of carotid plaques in type 2 diabetes mellitus patients. Conclusion: Our study presents novel evidence for main effects of MPO gene on type 2 diabetes mellitus susceptibility. Furthermore, our study supported the association between variants of oxidative stress–related genes ( GPX1 and MPO) and carotid plaques in type 2 diabetes mellitus patients, which indicated a modulation of type 2 diabetes mellitus–related vascular complication susceptibility by genetic predisposition.

scholarly journals Effect of Metformin on C-reactive Protein in Type 2 Diabetes Mellitus Patients

2021 ◽  
pp. 53-61
Author(s):  
P Selvi ◽  
Arul Amutha Elizabeth
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Vascular Complications ◽  
Diabetic Patients ◽  
C Reactive Protein ◽  
Metformin Therapy ◽  
Reactive Protein ◽  
Increased Risk ◽  
Hs Crp

Diabetes mellitus (DM) is a complex endocrinology disease which requires a meticulous understanding of its pathogenesis and its complications to subdue it. It has been riddled with extensive micro and macro vascular complications which by itself has its own set of pathogenesis. There is a link between DM and cardiovascular disease (CVD), which is the most important cause of morbidity and mortality in diabetic patients. Cardiovascular risk factors such as obesity, hypertension and dyslipidemia are more common in patients with DM, placing them at increased risk for cardiac events.  In addition, they have found biological mechanisms associated with DM that independently increases the risk of CVD in diabetic patients.Metformin is the most commonly used antidiabetic agent derived from Gallegaofficinalis. Metformin provided greater protection against macro vascular complications than would be expected from its effects upon glycemic control alone. Hence this study evaluated the anti-inflammatory effect of metformin on C Reactive Protein (CRP) in patients. In this study fifty type 2 diabetes patients were enrolled in the study including 23 males and 27 females with mean age 40±4.33. FBS and PPBS baseline values expressed as Mean ± SD were 138.06±17.12 mg/dl and 223.12±30.63 mg/dl respectively. After 6 months of metformin therapy, FBS and PPBS were 91.64±10.55 mg/dl and 133.88±7.99 mg/dl respectively. HBA1C baseline value expressed as Mean ± SD was 7.966±0.85 %. After 6 months of metformin therapy, HBA1C improved to 6.8±0.93.hs-CRP baseline value expressed as Mean±SD was 3.4±1.16 mg/L. After 6 months of metformin therapy, hs - CRP effectively reduced to 1.7±0.81 mg/L. Prompt treatment intensification in such cases may thus be sensible. Further studies are needed to identify predictors of metformin treatment response, especially focusing on hs-CRP levels, lipid levels and genetic factors.

scholarly journals Heart failure in diabetes: From an increased risk to a treatment target

2018 ◽  
Vol 21 (5) ◽  
pp. 399-403 ◽  
Author(s):  
Eberhard Standl
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cardiovascular Risk ◽  
Glycaemic Control ◽  
Treatment Target ◽  
Poor Glycaemic Control ◽  
Increased Risk

Heart failure (HF) is one of the most common comorbidities of type 2 diabetes mellitus (T2DM) and poor glycaemic control can worsen the HF outcomes and increase the risk of hospitalisations. With the entry of several antihyperglycaemic agents for the management of T2DM over the last decade, there has been an increasing concern regarding the cardiovascular (CV) safety profile of these agents. In view of this, FDA mandated the demonstration of cardiovascular risk-benefit profile of these agents through specifically designed CV outcome trials. Although we have several findings from these trials, none of them included HF as a primary endpoint indicating the need of trials focusing on HF. Here, we briefly discuss the results of the CV outcome trials in the context of HF.

Abstract 15516: Predicting Heart Failure Hospitalization in Type 2 Diabetes Mellitus: Validation of the TRS-HFDM Score in the ACCORD Trial

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Malik Elharram ◽  
Thao Huynh ◽  
Jiayi Ni ◽  
João P Ferreira ◽  
Abhinav Sharma
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Risk Score ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Event Rates

Background: Patients with type 2 diabetes mellitus (T2DM) are at an increased risk for developing heart failure (HF), and clinical models are needed to identify patients with a greater risk for HF hospitalization (HHF). The Thrombolysis in Myocardial Infarction Risk Score for Heart Failure in Diabetes (TRS-HFDM) was recently developed and validated to predict HHF in patients with T2DM in two large clinical trials (SAVOR-TIMI 53 and DECLARE-TIMI 58). We aimed to validate the TRS-HFDM in another cohort of patients with T2DM. Methods: We validated the TRS-HFDM score in 5,123 patients with T2DM for fatal or non-fatal HHF in the placebo arm of the ACCORD (Action to Control Cardiovascular Risk in Diabetes Study Group). The TRS-HFDM included: prior HF, history of atrial fibrillation, coronary artery disease, estimated glomerular filtration rate, and urine albumin-to-creatinine ratio. We evaluated discrimination with the Harrell C index, and calibration by comparing observed event rates for HHF with predicted risk, and the Nam-D’Agostino statistic. Results: During a mean follow up of 4.8 years, 212 patients (4.14%) experienced at least one HHF. The mean age was 63 ±6.7 years, and 38% were female. The baseline hemoglobin A1C was 8.3%, and 36% were on insulin. The ACCORD patients had less comorbidities with a lower proportion of patients with renal dysfunction (8% vs. 16% vs. 17%), established cardiovascular disease (35% vs.79% vs. 41%) and pre-existing HF (5% vs. 13% vs. 10%) compared to patients enrolled in the SAVOR-TIMI 53 and DECLARE TIMI-58 trials respectively. In our cohort, the TRS-HFDM score predicted well HHF events with a Harrel C index of 0.78. The integer-based score was well calibrated, with the observed Kaplan-Meier HHF rates closely predicting the Kaplan-Meier event rates at the end follow up (Nam D`Agostino test: 65.39 (p<0.0001). Discussion: Our findings confirm the applicability of the TRS-HFDM in a large cohort of patients with T2DM with less high-risk features than the SAVOR-TIMI 53 and DECLARE-TIMI 58 populations. Future validation of this risk score in observational cohort studies is needed to evaluate its external validity in a general clinical setting.

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