Diabetes Mellitus and Heart Failure.
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ABSTRACT:
SUBMITTER: Tousoulis D
PROVIDER: S-EPMC6159396 | biostudies-other | 2014 Jul
REPOSITORIES: biostudies-other
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Project description:Diabetes and heart failure are closely related: patients with diabetes have an increased risk of developing heart failure and those with heart failure are at higher risk of developing diabetes. Furthermore, antidiabetic medications increase the risk of mortality and hospitalisation for heart failure in patients with and without pre-existing heart failure. When the two diseases are considered individually, heart failure has a much poorer prognosis than diabetes mellitus; therefore heart failure has to be a priority for treatment in patients presenting with the two conditions, and the diabetic patient with heart failure should be managed by the heart failure team. No specific randomised clinical trials have been conducted to test the effect of cardiovascular drugs in diabetic patients with heart failure, but a wealth of evidence suggests that all interventions effective at improving prognosis in patients with heart failure are equally beneficial in patients with and without diabetes. The negative effect of glucose-lowering agents in patients with heart failure or at increased risk of heart failure has become evident after the withdrawal of rosiglitazone, a thiazolidinedione, from the EU market due to evidence of increased risk of cardiovascular events and hospitalisations for heart failure. An important issue that remains unresolved is the optimal target level of glycated haemoglobin, as recent studies have demonstrated significant reductions in total mortality, morbidity and risk of heart failure despite achieving HbA1c levels similar to those observed in the UKPDS study conducted some decades ago. Meta-analyses showed that intensive glucose lowering is not associated with any significant reduction in cardiovascular risk but conversely results in a significant increase in heart failure risk. Different medications have different risk: benefit ratios in diabetic patients with heart failure; therefore, the heart failure team must judge the required intensity of glycaemic control, the type and dose of glucose lowering agents and any change in glucose-lowering therapy, according to the clinical conditions present.
| S-EPMC5494155 | biostudies-other
Project description:Type 2 diabetes mellitus (T2DM) is a metabolic disease associated with several comorbidities, including cardiac dysfunction leading to heart failure with preserved ejection fraction (HFpEF), in turn resulting in T2DM-induced cardiomyopathy (T2DM-CM). However, the molecular mechanisms underlying the development of T2DM-CM are poorly understood. It is hypothesized that molecular alterations in myopathic genes induced by diabetes promote the development of HFpEF, whereas cardiac myosin inhibitors can rescue the resultant T2DM-induced cardiomyopathy. To test this hypothesis, a Leptin receptor-deficient db/db homozygous (Lepr db/db) mouse model was used to define the pathogenesis of T2DM-CM. Echocardiographic studies at 4 and 6 months revealed that Lepr db/db hearts started developing cardiac dysfunction by four months, and left ventricular hypertrophy with diastolic dysfunction was evident at 6 months. Strikingly, the level of cardiac myosin binding protein-C phosphorylation was significantly increased in Lepr db/db mouse hearts. RNA-seq data analysis, followed by functional enrichment, revealed the differential regulation of genes related to cardiac dysfunction in Lepr db/db heart tissues. Finally, using isolated skinned papillary muscles and freshly isolated cardiomyocytes, CAMZYOS (mavacamten, which is a prescription heart medicine used for symptomatic obstructive hypertrophic cardiomyopathy treatment (herein after denotes as MYK-461), was tested for its ability to rescue T2DM-CM. Compared with controls, MYK-461 significantly reduced force generation in papillary muscle fibers and cardiomyocyte contractility in the db/db group. This line of evidence shows that 1) T2DM-CM is associated with hyperphosphorylation of cardiac myosin binding protein-C and 2) MYK-461 significantly lessened disease progression, suggesting its promise as a therapeutic treatment for HFpEF.
2024-08-01 | GSE235934 | GEO
Project description:Epidemiological data on the association between body mass index (BMI) and heart failure (HF) risk among diabetic patients are rare.We performed a prospective cohort study of risk for HF among 31 155 patients with type 2 diabetes mellitus (11 468 men and 19 687 women). Cox proportional hazards regression models were used to estimate the association of different levels of BMI with HF risk. During a mean follow-up of 7.8 years, 5834 subjects developed HF (2379 men and 3455 women). The multivariable-adjusted (age, race, smoking, income, and type of insurance) hazard ratios of HF associated with BMI levels (18.5-22.9, 23-24.9, 25-29.9 [reference group], 30-34.9, 35-39.9, and ?40 kg/m(2)) at baseline were 0.95, 1.00, 1.00, 1.16, 1.64, and 2.02 (Ptrend<0.001) for men and 1.16, 1.16, 1.00, 1.23, 1.55, and 2.01 (Pnonlinear<0.001) for women, respectively. When we used an updated mean value of BMI, the association of HF risk with BMI did not change. When stratified by age, race, smoking status, and use of antidiabetic drugs, the positive associations among men and the J-shaped associations among women were still present.Our study suggests a positive association between BMI and HF risk among men and a J-shaped association between BMI and HF risk among women with type 2 diabetes mellitus.
| S-EPMC4586150 | biostudies-literature
Project description:AIMS:Sarcolipin (SLN) is a key regulator of sarcoplasmic reticulum calcium-ATPase (SERCA)2a, which handles intracellular calcium re-uptake. This study was aimed to investigate the involvement of SLN in post-myocardial infarction (MI) heart failure (HF) in diabetes. METHODS AND RESULTS:Diabetes/MI rat models were established. Altered SLN expression in diabetic hearts was screened out by microarray. A myocardiotropic viral vector was used to deliver siRNA to silence SLN. DNA methylation was evaluated by bisulfite sequencing. Cardiac functions were evaluated by invasive haemodynamic examinations. The SERCA2a activity, cytoplasmic calcium concentration ([Ca2+ ]i ), calcium spark, and myocyte contraction were detected. Correlation between HF and diabetes was analysed in a cohort consisted of 101 ST-segment elevated myocardial infarction (STEMI) patients between 2017 and 2019 [53.54 ± 4.64 years old; 61.4% male gender; HbA1c% 6.15 ± 2.00; and left ventricular ejection fraction (LVEF%) 40.64 ± 3.20%]. SLN expression was evaluated in left ventricular tissue sample from six STEMI patients complicated with diabetes and six STEMI patients without diabetes. Expressions of DNA methyltransferase 1a and DNA methyltransferase 3 were reduced in diabetic hearts, leading to down-regulation of SLN promoter methylation, resulting in increased SLN expression in rats. Impaired heart systolic functions were found in experimental diabetic MI rats, which were attenuated by SLN silencing. SERCA2a activity reduction and [Ca2+ ]i elevation were attenuated by SLN silencing in diabetic animal hearts and high-glucose incubated primary myocytes. SLN silencing suppressed calcium sparks and improved contraction and sarcoplasmic reticulum calcium re-uptake in high-glucose incubated primary myocytes. Expression of SLN was up-regulated in LV sampled from STEMI patients complicated with diabetes compared with non-diabetic ones (P < 0.05). LVEF% was reduced in STEMI patients complicated with diabetes compared with non-diabetic ones (P < 0.01). HbA1c% and LVEF% was related (r = -0.218, P = 0.028). Increased HbA1c% was correlated with reduced LVEF% after adjustment for age, sex, body mass index, cigarette smoking, creatinine, UA, low density lipoprotein, K+ , Na+ , and troponin I (adjusted odds ration = 0.75, 95% confidence interval 0.62-0.90, P = 0.002). CONCLUSIONS:Diabetes increases the vulnerability of STEMI patients to post-MI HF by down-regulating SLN promoter methylation, which further regulates SERCA2a activity via increasing cardiac SLN expression.
| S-EPMC7373908 | biostudies-literature
Project description:Diabetes mellitus (DM) is associated with a higher risk of heart failure hospitalization and mortality in patients with heart failure with preserved ejection fraction (HFpEF). Using SomaScan assays and proteomics analysis of plasma from participants in the TOPCAT (Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist) trial and the Penn Heart Failure Study, this study identified 10 proteins with significantly different expression in patients with HFpEF and DM. Of these, apolipoprotein M was found to mediate 72% (95% CI: 36% to 100%; p < 0.001) of the association between DM and the risk of cardiovascular death, aborted cardiac arrest, and heart failure hospitalization.
| S-EPMC7907637 | biostudies-literature
Project description:Background Microvascular disease (MVD) is a potential contributor to the pathogenesis of diabetes mellitus-related cardiac dysfunction. However, there is a paucity of data on the link between MVD and incident heart failure (HF) in type 2 diabetes mellitus. We examined the association of MVD with incident HF in adults with type 2 diabetes mellitus. Methods and Results A total of 4095 participants with type 2 diabetes mellitus and free of HF were assessed for diabetes mellitus-related MVD including nephropathy, retinopathy, or neuropathy at baseline in the Look AHEAD (Action for Health in Diabetes) study. Incident HF events were prospectively assessed and adjudicated using hospital and death records. Cox models were used to generate hazard ratios and 95% CIs for HF. Of 4095 participants, 34.8% (n=1424) had MVD, defined as the presence of ≥1 of nephropathy, retinopathy, or neuropathy at baseline. Over a median of 9.7 years, there were 117 HF events. After adjusting for relevant confounders, participants with MVD had a 2.5-fold higher risk of incident HF than those without MVD (hazard ratio, 2.54; 95% CI, 1.73-3.75). This association remained significant after additional adjustment for interval development of coronary artery disease (hazard ratio, 2.42; 95% CI, 1.64-3.57). The hazard ratios for HF by type of MVD were 2.22 (95% CI, 1.51-3.27), 1.30 (95% CI, 0.72-2.36), and 1.33 (95% CI, 0.86-2.07) for nephropathy, retinopathy, and neuropathy, respectively. CONCLUSIONS MVD is associated with an excess HF risk in individuals with type 2 diabetes mellitus after adjusting for other known risk factors. Our findings underscore the contribution of MVD to the development of diabetes mellitus-related HF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00017953.
| S-EPMC8477890 | biostudies-literature
Project description:BackgroundAntidiabetic therapies have shown disparate effects on hospitalization for heart failure (HHF) in clinical trials. This study developed a prediction model for HHF in type 2 diabetes mellitus (T2DM) using real world data to identify patients at high risk for HHF.HypothesisType 2 diabetics at high risk for HHF can be identified using information generated during usual clinical care.MethodsThis electronic medical record- (EMR-) based retrospective cohort study included patients with T2DM free of HF receiving healthcare through a single, large integrated healthcare system. The primary endpoint was HHF, defined as a hospital admission with HF as the primary diagnosis. Cox regression identified the strongest predictors of HHF from 80 candidate predictors derived from EMRs. High risk patients were defined according to the 90th percentile of estimated risk.ResultsAmong 54,452 T2DM patients followed on average 6.6 years, estimated HHF rates at 1, 3, and 5 years were 0.3%, 1.1%, and 2.0%. The final 9-variable model included: age, coronary artery disease, blood urea nitrogen, atrial fibrillation, hemoglobin A1c, blood albumin, systolic blood pressure, chronic kidney disease, and smoking history (c = 0.782). High risk patients identified by the model had a >5% probability of HHF within 5 years.ConclusionsThe proposed model for HHF among T2DM demonstrated strong predictive capacity and may help guide therapeutic decisions.
| S-EPMC7068070 | biostudies-literature
Project description:Background: Three sodium-glucose cotransporter-2 inhibitors (SGLT2i), canagliflozin, dapagliflozin and empagliflozin, successfully reduced hospitalization for heart failure (HF) in patients with type 2 diabetes mellitus (T2DM). It remains unclear, however, whether the efficacy of the 3 SGLT2i for HF in T2DM patients is similar. Methods and Results: Eighty-one T2DM patients hospitalized due to decompensated HF were enrolled. After treatment for HF, one of the 3 SGLT2i was non-randomly used, and clinical parameters for HF and T2DM were followed for 7 days. The attending physician was allowed to adjust the dose of furosemide. No differences were observed between the 3 groups in the increase of glycosuria, or in the decreases of body weight and blood pressure 7 days after SGLT2i (interaction P>0.05). Urine volume was similarly increased on day 1, and returned to the baseline on day 7 in each group. Decrease in B-type natriuretic peptide and increase in plasma renin activity were significant in each group. Plasma aldosterone concentration, however, was significantly increased in the empagliflozin and canagliflozin groups (P<0.01, respectively), but not in the dapagliflozin group. Additionally, plasma noradrenaline was significantly increased in the empagliflozin group (P<0.01), but not in the canagliflozin and dapagliflozin groups. Conclusions: The neurohumoral responses to the 3 SGLT2i are different under similar volume correction in HF patients with T2DM.
| S-EPMC7897568 | biostudies-literature
Project description:Type 2 diabetes mellitus is an independent risk factor for heart failure development, but the relationship between incident heart failure and antecedent glycemia has not been evaluated.The Genetics of Diabetes Audit and Research in Tayside Study study holds data for 8683 individuals with type 2 diabetes mellitus. Dispensed prescribing, hospital admission data, and echocardiography reports were linked to extract incident heart failure cases from December 1998 to August 2011. All available HbA1c measures until heart failure development or end of study were used to model HbA1c time-dependently. Individuals were observed from study enrolment until heart failure development or end of study. Proportional hazard regression calculated heart failure development risk associated with specific HbA1c ranges accounting for comorbidities associated with heart failure, including blood pressure, body mass index, and coronary artery disease. Seven hundred and one individuals with type 2 diabetes mellitus (8%) developed heart failure during follow up (mean 5.5 years, ±2.8 years). Time-updated analysis with longitudinal HbA1c showed that both HbA1c <6% (hazard ratio =1.60; 95% confidence interval, 1.38-1.86; P value <0.0001) and HbA1c >10% (hazard ratio =1.80; 95% confidence interval, 1.60-2.16; P value <0.0001) were independently associated with the risk of heart failure.Both high and low HbA1c predicted heart failure development in our cohort, forming a U-shaped relationship.
| S-EPMC4366571 | biostudies-literature
Project description:Heart failure is the most common comorbidity of diabetes. The incidence of heart failure in patients with diabetes is about 9%-22%, which is four times higher Than that in patients without diabetes. Heart failure and diabetes are collectively associated with increased morbidity and mortality compared to either condition alone. Several epidemiological studies have demonstrated an increased risk of heart failure in patients with diabetes; moreover, poor glycemic control accounts for the increased risk of heart failure. At present, several oral (metformin, sulfonylureas, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, etc.) as well as injectable (insulins, glucagon-like peptide 1 receptor agonists) antidiabetic agents are available. However, optimal treatment strategy to achieve adequate glycemic control in patients with type 2 diabetes mellitus (T2DM) and heart failure has not been well studied. In the view of rising prevalence of heart failure in patients with diabetes mellitus, clinicians need to understand the potential implications of antidiabetic agents in patients with heart failure. A group of experts from across India were involved in a consensus meeting in Pondicherry during the National Insulin Summit in November 2015. They evaluated agents currently available for the treatment of diabetes looking at existing scientific evidence relevant to each class of therapy. In addition, the existing guidelines and prescribing literature available with all these agents were also reviewed. Findings from the expert evaluations were then factored into the national context incorporating personal experience and common clinical practices in India. The purpose of this consensus document is to assist the clinicians while treating patients with T2DM and heart failure.
| S-EPMC5477452 | biostudies-other