Non-diabetic Chronic Heart Failure Patients Research Articles

Relationship between fasting serum C-peptide level and heart function in patients with or without diabetes mellitus and chronic heart failure

Objective To evaluate the relationships between admission fasting serum C-peptide concentration and cardiac function status in chronic heart failure (CHF) patients with or without diabetes. Methods From July 2017 to December 2018, 262 CHF patients with or without diabetes in the Department of Cardiology of Pudong hospital in Shanghai were analyzed.Their cardiac function was classified as New York Heart Association (NYHA) grade Ⅱ to Ⅳ, and they were divided into diabetes group (80 cases) and non diabetes group (182 cases). At the same time, 62 subjects without diabetes and heart disease were randomly selected as the control group.To analyze the relationship between fasting serum C-peptide level and cardiac function in diabetic and nondiabetic CHF patients. Results (1)The fasting plasma glucose and serum C-peptide concentrations of diabetes group paitents were(8.7±2.9) mmol/L and(0.78±0.67) nmol/L respectively, the nondiabetes group paitents were(5.8±1.67) mmol/L and(0.56±0.61)nmol/L respectively, the control group were(5.1±0.69) mmol/L and(0.16±0.12)nmol/L respectively.The difference in the three groups was statistically significant(all P 0.05). (2) In all patients with heart failure, diabetes mellitus and non diabetes heart failure, the levels of serum C-peptide were (1.05±0.85), (1.17±0.82), (0.99±0.86) nmol/L in NYHA Ⅳ group, and (0.53±0.22), (0.52±0.20), (0.54±0.23) nmol/L in NYHA Ⅲ group, and (0.32±0.09), (0.32±0.11), (0.31±0.09) nmol/L in NYHA Ⅱ group.After adjustment of age, gender, smoking, insulin secretion and hypoglycemic drugs, body mass index, blood pressure, total bilirubin (TBIL), alanine aminotransferase (ALT), creatinine, blood glucose, blood lipid, white blood cell count (WBC) and hemoglobin level by covariance analysis, all patients with heart failure The level of serum C-peptide in NYHA Ⅳ group was significantly higher than that in Ⅲ group (all P 0.05) (3) Using multiple linear regression analysis, the adjustment factors included age, gender, smoking, BMI, blood pressure, TBIL, alt, creatinine, blood glucose, blood lipid, WBC and hemoglobin levels.The results showed that the serum C-peptide level was positively correlated with pro-BNP in all patients with heart failure, diabetes and non diabetes heart failure (β: 0.006, 95%CI -0.016-0.028 , P=0.007; β: 0.117, 95%CI-0.042-0.277 , P=0.006; β: 0.411, 95%CI-0.149-0.971 , P=0.023), negatively correlated with LVEF(β: -0.122, 95%CI-0.285-0.041, P=0.004; β: -0.008, 95%CI-0.032-0.016, P=0.010; β: -0.065, 95%CI-0.139-0.011, P=0.036). Conclusion The level of fasting serum C-peptide was significantly increased in patients with CHF and non-diabetic patients, and was related to the severity of heart failure. Key words: Chronic heart failure; Diabetes mellitus; Serum C-peptide; N-terminal B-type natriuretic peptide; Cardiac function

Effect of liraglutide on myocardial glucose uptake and blood flow in stable chronic heart failure patients: A double-blind, randomized, placebo-controlled LIVE sub-study

BackgroundThe glucagon-like peptide-1 analog liraglutide increases heart rate and may be associated with more cardiac events in chronic heart failure (CHF) patients. We studied whether this could be ascribed to effects on myocardial glucose uptake (MGU), myocardial blood flow (MBF) and MBF reserve (MFR). Methods and ResultsCHF patients with left ventricular ejection fraction ≤45% and without type 2 diabetes were randomized to liraglutide (N = 18) 1.8 mg once daily or placebo (N = 18) for 24 weeks in a double-blinded design. Changes in MGU during an oral glucose tolerance test (OGTT) and changes in MBF and MFR from baseline to follow-up were measured quantitatively by 18F-FDG and 15O-H2O positron emission tomography. Compared with placebo, liraglutide reduced weight (P = 0.03), HbA1c (P = 0.03) and the 2-hour glucose value during the OGTT (P = 0.004). Despite this, changes in MGU (P = 0.98), MBF (P = 0.76) and MFR (P = 0.89) from baseline to follow-up did not differ between groups. Furthermore, there was no association between the level of insulin resistance at baseline and changes in MGU in patients treated with liraglutide. ConclusionLiraglutide did not affect MGU, MBF, or MFR in non-diabetic CHF patients. Any potential increase in cardiac events in these patients seems not to involve changes in MGU, MBF, or MFR. Trial RegistrationTrial registry: http://www.ClinicalTrials.org. Identifier: NCT01472640. Url: https://clinicaltrials.gov/ct2/show/NCT01472640?term=NCT01472640&rank=1

Interdisciplinary approach to compensation of hypoglycemia in diabetic patients with chronic heart failure.

Diabetes mellitus is a chronic disease requiring lifelong control with hypoglycemic agents that must demonstrate excellent efficacy and safety profiles. In patients taking glucose-lowering drugs, hypoglycemia is a common cause of death associated with arrhythmias, increased thrombus formation, and specific effects of catecholamines due to sympathoadrenal activation. Focus is now shifting from merely glycemic control to multifactorial approach. In the context of individual drugs and classes, this article reviews interdisciplinary strategies evaluating metabolic effects of drugs for treatment of chronic heart failure (CHF) which can mask characteristic hypoglycemia symptoms. Hypoglycemia unawareness and cardiac autonomic neuropathy are discussed. Data suggesting that hypoglycemia modulates immune response are reviewed. The potential role of gut microbiota in improving health of patients with diabetes and CHF is emphasized. Reports stating that nondiabetic CHF patients can have life-threatening hypoglycemia associated with imbalance of thyroid hormones are discussed. Regular glycemic control based on HbA1c measurements and adequate pharmacotherapy remain the priorities in diabetes management. New antihyperglycemic drugs with safer profiles should be preferred in vulnerable CHF patients. Multidrug interactions must be considered. Emerging therapies with reduced hypoglycemia risk, telemedicine, sensor technologies, and genetic testing predicting hypoglycemia risk may help solving the challenges of hypoglycemia in CHF patients with diabetes. Interdisciplinary work may involve cardiologists, diabetologists/endocrinologists, immunologists, gastroenterologists, microbiologists, nutritionists, imaging specialists, geneticists, telemedicine experts, and other relevant specialists. This review emphasizes that systematic knowledge on pathophysiology of hypoglycemia in diabetic patients with CHF is largely lacking and the gaps in our understanding require further discoveries.

Circulating endothelial-derived apoptotic microparticles and insulin resistance in non-diabetic patients with chronic heart failure.

The objective of this study was to assess the relationship between insulin resistance and apoptotic endothelial-derived microparticles (EMPs) in patients with chronic heart failure (CHF). The study involved 300 CHF patients (186 males) aged 48-62 years with angiographically proven coronary artery disease and/or previously defined myocardial infarction. Insulin resistance was assessed by the homeostasis model assessment for insulin resistance (HOMA-IR). EMPs phenotype was determined by flow cytofluorometry. Depending on HOMA-IR cut-off point (over and <2.77 mmol/L×μU/mL) all patients were divided into two cohorts with (n=171) or without (n=129) IR, respectively. Circulating EMPs were higher in CHF patients with IR than in patients without IR. Interestingly, EMPs were directly related to NYHA functional class of CHF, HOMA-IR, NT-pro-BNP, hs-CRP and BMI. There was a significant association between the level of EMPs and HbA1c, gender (r=0.318, p<0.001 for male), age and smoking. On univariate and multivariate regression analysis we found that the NYHA class of CHF,NT-pro-BNP, hs-CRP, and left ventricular ejection fraction (LVEF) appeared to be independent predictors of increased circulatory apoptotic EMPs. The addition of HOMA-IR to the standard model (NYHA class CHF) improved the relative IDI by 19.9% for increased EMPs. For category-free NRI, 10% of events and 24% of non-events were correctly reclassified by the addition of HOMA-IR to the standard model for increased circulating EMPs. IR may be a contributing factor increasing circulating levels of apoptotic EMPs in non-diabetic CHF patients.

Relationship between circulating endothelial progenitor cells and insulin resistance in non-diabetic patients with ischemic chronic heart failure

AimThe objective of this study was to assess a relationship between insulin resistance (IR) and counts of CD45−CD34+, CD14+CD309+, and CD14+CD309+Tie2+ phenotyped circulating endothelial progenitor cells (EPCs) in patients with ischemic chronic heart failure (CHF). MethodsThe study involved 300 CHF patients (186 males) aged 48–62 years with angiografically proven coronary artery disease and/or previously defined myocardial infarction. Insulin resistance was assessed by the homeostasis model assessment for insulin resistance (HOMA-IR). EPC populations were phenotyped by flow cytofluorimetry. ResultsCirculating EPCs counts were statistically significantly lower in CHF patients with IR than in patients without IR. We found that the most valuable multivariable predictors of the depletion of the CD45+CD34+ EPCs were NT-pro-brain natriuretic peptide (BNP) (1.32; 95% CI=1.19–2.77; P=0.001), left ventricular ejection fraction (OR=1.30; 95% CI=1.09–1.60; P=0.002), NYHA class (OR=1.12; 95% CI=1.02–1.19; P=0.001). NT-pro-BNP (OR=1.45; 95% CI=1.15–2.90; P=0.003), left ventricular ejection fraction (OR=1.32; 95% CI=1.11–1.65; P=0.001) were found as powerful predictors for depletion in CD45−CD34+ EPCs. We also identified six independent variables with high predictive value for depletion of CD14+CD309+ EPCs: NT-pro-BNP (OR=1.41; 95% CI=1.15–2.90; P=0.003), left ventricular ejection fraction (OR=1.18; 95% CI=1.10–1.76; P=0.036), NYHA class (OR=1.15; 95% CI=1.07–1.22; P=0.001), hs-C reactive protein (OR=1.02; 95% CI=1.01–1.05; P=0.012). As independent multivariable predictors for depletion in CD14+CD309+Tie2+ EPCs were selected five variables: NT-pro-BNP (OR=1.65; 95% CI=1.44–4.70; P=0.006), left ventricular ejection fraction (OR=1.07; 95% CI=1.02–1.12; P=0.018), NYHA class (OR=1.13; 95% CI=1.06–1.21; P=0.001), hs-C-reactive protein (OR=1.08; 95% CI=1.03–1.16; P=0.002). ConclusionIR may be an additional factor contributing decreased circulating level of proangiogenic EPCs in non-diabetic CHF patients.

Prevalence of cachexia in chronic heart failure and characteristics of body composition and metabolic status

The prevalence of cardiac cachexia has previously been estimated to 8-42 %. However, novel treatment strategies for chronic heart failure (CHF) have improved and decreased morbidity and mortality. Therefore, we aimed to reassess the prevalence of cachexia in an outpatient CHF clinic and to characterize a CHF population with and without cachexia with respect to body composition and related biomarkers. From 2008 to 2011, we screened 238 optimally treated, non-diabetic CHF patients for cardiac cachexia, defined as unintentional non-oedematous weight loss of >5 % over ≥6 months. CHF patients (LVEF <45 %) with cachexia (n = 19) and without (n = 19) were compared to controls with prior myocardial infarction and left ventricular ejection fraction (LVEF) >45 % (n = 19). The groups were matched for age, sex, and kidney function. Body composition was assessed by dual energy X-ray absorptiometry. The prevalence of cachexia was 10.5 %. Abdominal fat ± SD (%) was reduced in cachectic CHF: 27.4 ± 10.0 versus 37.5 ± 10.6 % (CHF, no cachexia) and 40.6 ± 8.0 % (controls), (P < 0.001). NT-proBNP levels were inversely correlated to abdominal fat in a multivariate linear regression analysis adjusted for known predictors of NT-proBNP (LVEF and NYHA); (β = -0.28; P = 0.018). Myostatin levels were reduced in cachectic CHF compared to controls (P = 0.013). The prevalence of cachexia in stable CHF, treated according to recent guidelines, is lower than previously anticipated. Body alterations in cachexia consist mainly of reduced abdominal fat mass, and its inverse correlation to NT-proBNP suggests involvement of abdominal lipolysis. Our data do not support a role of circulating myostatin as a biomarker for muscle wasting.

The effect of metformin on insulin resistance and exercise parameters in patients with heart failure

Chronic heart failure (CHF) is an insulin-resistant state. The degree of insulin resistance (IR) correlates with disease severity and is associated with reduced exercise capacity. In this proof of concept study, we have examined the effect of metformin on IR and exercise capacity in non-diabetic CHF patients identified to have IR. In a double-blind, placebo-controlled study, 62 non-diabetic IR CHF patients (mean age, 65.2 ± 8.0 years; male, 90%; left ventricular ejection fraction, 32.6 ± 8.3%; New York Heart Association class I/II/III/IV, 11/45/6/0) were randomized to receive either 4 months of metformin (n = 39, 2 g/day) or matching placebo (n = 23). IR was defined by a fasting insulin resistance index (FIRI) ≥2.7. Cardiopulmonary exercise testing and FIRI were assessed at baseline and after 4 months of intervention. Compared with placebo, metformin decreased FIRI (from 5.8 ± 3.8 to 4.0 ± 2.5, P < 0.001) and resulted in a weight loss of 1.9 kg (P < 0.001). The primary endpoint of the study, peak oxygen uptake (VO(2)), did not differ between treatment groups. However, metformin improved the secondary endpoint of the slope of the ratio of minute ventilation to carbon dioxide production (VE/VCO(2) slope), from 32.9 ± 15.9 to 28.1 ± 8.8 (P = 0.034). In the metformin-treated group, FIRI was significantly related to the reduction of the VE/VCO(2) slope (R = 0.41, P = 0.036). Metformin treatment significantly improved IR but had no effect on peak VO(2), the primary endpoint of our study. However, metformin treatment did result in a significant improvement in VE/VCO(2) slope. NCT00473876.

Insulin Resistance Is Highly Prevalent and Is Associated With Reduced Exercise Tolerance in Nondiabetic Patients With Heart Failure

The purpose of this study was to establish the prevalence of insulin resistance (IR) among nondiabetic chronic heart failure (CHF) patients and to seek factors associated with IR in CHF, including the relationship of IR to functional class, exercise capacity, and disease severity in CHF. Several lines of evidence suggest that CHF is an IR state. The prevalence of IR in CHF and its relation to CHF have not been fully defined. Fasting insulin resistance index (FIRI) was assessed in a cohort of 129 consecutive CHF patients (mean age 69.2 +/- 10.4 years; 76% males; body mass index 27.4 +/- 4.4 kg/m(2)). Patients underwent cardiopulmonary exercise testing and peripheral endothelial function testing by reactive hyperemia peripheral arterial tonometry (RH-PAT). Prevalence of IR as defined by FIRI > or =2.7 was 61% in our cohort of CHF patients. There was a significant correlation between IR and waist circumference (r = 0.37; p < 0.01), serum triglycerides (r = 0.34; p < 0.01), high-density lipoprotein cholesterol (r = -0.22; p = 0.02), and serum leptin (r = 0.39; p = 0.03). Insulin resistance increased significantly with worsening New York Heart Association functional class (p < 0.01). The CHF patients with IR had a significantly lower exercise capacity and peak oxygen consumption than patients with an FIRI <2.7. The RH-PAT ratio was significantly lower in CHF patients with IR compared with CHF patients with an FIRI <2.7 (1.6 +/- 0.3 vs. 2.0 +/- 0.5; p < 0.05). Insulin resistance is highly prevalent among nondiabetic CHF patients and is associated with decreased exercise capacity in patients with CHF. (Insulin Resistance: Heart Failure; NCT00486967).

Reduced glucose transporter GLUT4 in skeletal muscle predicts insulin resistance in non-diabetic chronic heart failure patients independently of body composition

Background In chronic heart failure (CHF) skeletal muscle insulin resistance occurs independently of etiology and contributes to impaired energy metabolism. GLUT4, the predominant glucose transporter in the skeletal muscle promotes the rate-limiting step of glucose utilization in skeletal muscle. The significance of skeletal muscle GLUT4 in patients with CHF has not been studied in detail. Methods In patients with CHF and free of diabetes mellitus ( n = 29; mean NYHA class 2.3 ± 0.1, peak VO 2 18.8 ± 1.1 mL/kg/min) and healthy control subjects of similar age ( n = 7), GLUT4 protein was assessed from percutaneous skeletal muscle biopsies. Skeletal muscle insulin sensitivity was assessed by intravenous glucose tolerance testing using a minimal modeling technique. Body composition was analyzed by dual energy X-ray absorptiometry (DEXA) scanning. Results Skeletal muscle GLUT4 was lower in CHF patients than in controls (0.75 ± 0.07 vs 1.24 ± 0.19 density units, P < 0.01) and decreased in parallel to severity of CHF, being lowest in NYHA III/IV (0.596 ± 0.08, ANOVA P < 0.01 vs controls). GLUT4 was lower in patients with an ischemic etiology compared to dilated cardiomyopathy and controls (ANOVA P < 0.01). Patients and controls were similar for global parameters of body composition (weight: 78 ± 4 vs 76 ± 4 kg, BMI 25.5 ± 0.8 vs 25.8 ± 1.5 kg/m 2), and total tissue amount and regional distribution of fat and lean tissue (all P > 0.2). Low GLUT4 predicted impaired insulin sensitivity, i.e. insulin resistance ( r = 0.55, P < 0.01). In multivariate analysis, GLUT4 levels predicted insulin sensitivity independently of age and parameters of body composition (including weight, BMI, and total and regional fat and lean tissue distribution). Conclusion In non-diabetic patients with CHF, skeletal muscle GLUT4 transport protein is reduced in parallel to disease severity, independently of body composition. Low skeletal muscle GLUT4 contributes to insulin resistance in CHF.

Abstract 3144: Prevalence Of Insulin Resistance Among Non-diabetic Chronic Heart Failure Patients And Its Relation To Disease Severity

Body: Background Purpose- There is increasing evidence of a reciprocal interrelationship between chronic heart failure (CHF) and insulin resistance (IR) such that IR may be pathophysiologically linked to the evolution of the disease in CHF. However, the prevalence of IR in the CHF population has not been fully defined. The purpose of this study was to establish the prevalence of IR among non-diabetic CHF patients and to assess its relation to disease severity. Methods- The homeostatic model of insulin resistance (HOMA-IR) was assessed in a cohort of 129 CHF patients; mean age (69.2±10.4 yrs) [range 30 –90 yrs], males 76%, CHF of ischemic etiology 82.2% and BMI (27.4±4.4kg/m2). All were on regular CHF medication. Patients underwent cardiopulmonary exercise testing and peripheral endothelial function testing by reactive hyperemia peripheral arterial tonometry (RH-PAT). Results- Prevalence of IR as defined by Fasting Insulin Resistance Index &gt;2.7 was 61% in CHF and was significantly higher than in the 23 subjects who were coronary artery disease controls without HF(P&lt;0.05). The degree of IR was not related to the etiology of CHF. There was a significant correlation between IR and serum triglyceride (r = 0.333, P&lt;0.01), HDL cholesterol (r = − 0.275, p&lt;0.05), impaired fasting glucose (r = 0.358, P&lt;0.01) and central obesity (r = 0.232, p&lt;0.01). The degree of IR was related to the exercise capacity and peak oxygen consumption (VO 2 ). Mean of IR increased significantly with worsening functional NYHA Classes I, II, III and IV [2.1, 2.9, 4.8, 8.9], (r = 0.437, p&lt;0.01). The IR patients had a significantly lower exercise duration (340 ±168.3 vs. 601 ±265.9 s, p&lt; 0.01) and peak VO 2 (6.4 ± 2.3 vs. 14.5 ±1.7 ml/kg per min, p&lt; 0.05). Exercise peak cardiac output determined by the inert gas re-breathing method was lower in patients with IR (5.2 ±1.2 vs. 9.2 ± 0.89 l/min, p&lt;0.05). Endothelial function as measured by RH-PAT decreased significantly in patients with IR compared to the patients with normal insulin sensitivity (1.64 ± 0.36 vs. 2.0 ± 0.53, p&lt;0.05I). Conclusion - These findings suggest that IR is highly prevalent among CHF patients and is associated with decreased exercise effort and capacity in patients with CHF. Targeting IR might represent a new strategy in the treatment of CHF.

Insulin Resistance in Heart Failure: Prevalence and Relation to Disease Severity

Insulin Resistance in Heart Failure: Prevalence and Relation to Disease Severity

Does Carvedilol Impair Insulin Sensitivity in Heart Failure Patients Without Diabetes?

Background An increased risk for impaired glucose tolerance or diabetes was shown in patients on β-blockers, whereas alpha1 blockers seem to have favorable effects on glycemic profile. In this study, the metabolic effect of carvedilol in nondiabetic patients with chronic heart failure (CHF) was evaluated. Methods and Results Twenty-eight nondiabetic CHF patients were enrolled. Before being started on carvedilol and on the highest tolerated dose, each patient underwent an oral glucose tolerance test and fasting insulin, glycohemoglobin, lipid concentrations were measured and insulin sensitivity indices (HOMA, ISI-gly, and ISI-composite) were calculated. An impaired glucose tolerance was found (2-hour glycemia 144 ± 42 mg/dL), with a fasting glycemia at upper limits of normal (108 ± 13 mg/dL) and no significant differences between basal and carvedilol treatment measurements. Fasting insulinemia significantly decreased during carvedilol treatment (13.6 ± 7.3 versus 9.8 ± 5.1 μU/mL; P = .022), with a reduction of the HOMA index (3.75 ± 1.95 versus 2.73 ± 1.47; P = 034) and an increase of the ISI-gly index (0.85 ± 0.22 versus 1.03 ± 0.31; P = .025). The lipoprotein profile did not significantly change. Conclusion Carvedilol might have some positive metabolic effects on increasing insulin sensitivity that would make it suitable for diabetic patients that have a worse prognosis than non diabetic patients with CHF.