scholarly journals Molecular biomarker profile of heart failure with mid-range and preserved ejection fraction in patients with type 2 diabetes

2020 ◽  
Vol 25 (10) ◽  
pp. 3967
Author(s):  
D. A. Lebedev ◽  
E. A. Lyasnikova ◽  
A. A. Vasilyeva ◽  
E. Yu. Vasilyeva ◽  
A. Yu. Babenko ◽  
...  

Aim. To study molecular biomarkers in patients with type 2 diabetes (T2D) in combination with heart failure with preserved (HFpEF) and mid-range ejection fraction (HFmrEF) and compare the data obtained with clinical characteristics of myocardial remodeling.Material and methods. The study included 42 patients with T2D (men — 53%, mean age — 60 years) with clinical manifestations of class II HF: 29 patients with HFpEF (group 1) and 13 patients with HFmrEF (group 2). The control group consisted of 13 healthy people, which were comparable in sex and age and had a normal body mass index (BMI). Patients received stable glucose-lowering and optimal drug therapy for HF for 3 months prior to enrollment in the study. Patients with HFpEF and HFmrEF were comparable in clinical and demographic parameters, had glycated hemoglobin (HbA ) of 8,5% and 8,8%, respectively (p>0,05), increased BMI or grade I-II obesity.We studied following biomarkers: NT-proBNP, highly sensitive C-reactive protein (hsCRP), sST2, galectin-3, procollagen type I C-terminal propeptide (PICP), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1).Results. Volumetric parameters of the left ventricle (LV),LV mass indexed to growth and NT-proBNP were higher in the group of HFpEF patients (p<0,05 for all). The concentrations of galectin-3, PICP were higher, and the MMP-9/TIMP-1 ratio decreased in patients with T2D compared with the control group (p<0,05 for all). PICP values were higher in patients with HFmrEF compared with patients with HFpEF (106,4 (85,4; 140,4) ng/ml vs 46,8 (12,6; 98,6 ng/ml), respectively, p=0,043). In patients with T2D and HF, a relationship was found between TIMP-1 andLV end-diastolic volume (r=-0,68; p=0,042).Conclusion. Patients with HFmrEF and T2D have higherLV volume and mass, higher concentrations of NT-proBNP and PICP in comparison with patients with HFpEF. The direction of MMP-9/TIMP-1 changes may reflect a decrease in antifibrotic processes. Further prospective studies on large samples using a multiple biomarker model are required in T2D and various HF phenotypes.

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
D. A. Lebedev ◽  
E. A. Lyasnikova ◽  
E. Yu Vasilyeva ◽  
A. Yu Babenko ◽  
E. V. Shlyakhto

As myocardial fibrosis might be an important contributor to the association of diabetes mellitus with left ventricular (LV) dysfunction and chronic heart failure (HF), we investigated the profile of some proinflammatory, profibrotic biomarkers in patients with type 2 diabetes mellitus (T2DM) at various stages of the cardiovascular disease continuum from absence of clinic since and symptoms to HF with preserved (HFpEF) and midrange ejection fraction (HFmrEF). Material and Methods. Sixty-two patients with T2DM (age 60 [55; 61]), 20 patients without clinical manifestations of HF and 2 groups with clinical manifestations of stable HF, 29 patients with HFpEF, and 13 patients with HFmrEF, were included in the study. The control group consisted of 13 healthy subjects and normal BMI. All patients underwent transthoracic echocardiography, laboratory assessment of N-terminal fragment of the brain natriuretic peptide (Nt-proBNP), highly sensitive C-reactive protein (hsCRP), soluble suppression of tumorigenesis-2 (sST2), galectin-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). Results. Patients with HFmrEF had higher values of LV volumetric parameters, indexed parameters of LV myocardial mass (LVMM), and higher concentrations of Nt-proBNP (all p < 0.05 ). The concentrations of galectin-3 were greater in patients with HFpEF and HFmrEF compared to patients without HF ( p = 0.01 and p = 0.03 , respectively). PICP and PICP/PIIINP ratio were greater in patients with HFmrEF compared to patients with HFpEF ( p = 0.043 and p = 0.033 , respectively). In patients with T2DM and HF, a relationship was found between galectin-3 and LVMM/body surface area ( r = − 0.58 , p = 0.001 ), PIIINP, TIMP-1, and LV end-diastolic volume ( r = − 0.68 and p = 0.042 and r = 0.38 and p = 0.02 , respectively). Conclusion. The dynamics at various stages of the cardiovascular disease continuum in the serum fibrosis markers may reflect an increase in fibrotic and decrease in antifibrotic processes already at the preclinical stage of HF. At the same time, the changes found in the circulating procollagen levels may indicate a shift in balance towards type I collagen synthesis in HFmrEF compared with HFpEF.


2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
E Martin Dorado ◽  
R Gonzalez Manzanares ◽  
J.C Castillo Dominguez ◽  
J Lopez Aguilera ◽  
J Perea ◽  
...  

Abstract Background Sodium-glucose cotransporter 2 (SGLT2) inhibitors have demonstrated to reduce the risk of hospitalization for heart failure (HF) in patients with type 2 diabetes mellitus (T2D). We aimed to assess the changes in N-terminal pro-B-type natriuretic peptide (NT-ProBNP) concentrations in a cohort of patients hospitalized for HF according to whether or not they received canagliflozin at discharge. Methods This cohort study included all patients with T2D admitted for HF from January 2017 to December 2019 in a single center. We excluded patients whose treatment with SGLT2 inhibitors were contraindicated (eGFR ≤45 ml/min/1.73 m2) and those who had other SGLT2 inhibitors than canagliflozin in their treatment at discharged. All patients had received a primary diagnosis of acute decompensated heart failure, including signs and symptoms of fluid overload and a concentration of NT-ProBNP of 1400 pg/mL at least. NT-ProBNP concentrations were collected at 3 months, 6 months, and 1 year after hospitalization with laboratory records if available. The aim of this study is to compare mean NT-ProBNP levels at hospital discharge and 3, 6 and 12 moths of follow-up in patients treated with and without canagliflozin. Results We included a total of 102 patients, 45 patients (44.1%) were prescribed canagliflozin and the remaining 57 (55.9%) were not prescribed any SGLT2 inhibitors (control group). There were no significant differences in clinical and comorbidities in both groups, except for age; slightly younger in the canagliflozin group (69,2±10,3 vs 73,2±11,1; p=0,04). Treatment at discharge was also similar, patients in the control group received more dipeptidyl peptidase-4 (DPP-4) inhibitors (21.1% vs 6.7%; p=0.04). Low rate of patients received sacubitril-valsartan (15,6%) in the canagliflozin group and 14% in the control group. More than a half of patients in both groups have HF with reduced ejection fraction. Mean levels of peptides were similar in both groups at hospital admission and discharge. During the first period of 3 months, we observed a decreased of NT-ProBNP concentration in both groups, but significantly inferior in canagliflozin group (p&lt;0,001). At 6 and 12 months, NT-ProBNP levels were practically maintained in patients treated with canagliflozin, whereas levels in patients in the control group were increased. Difference in both groups at a 12 month-period was significantly superior (p=0,004), with a median reduction of concentration levels at discharge of 64.3% in the canagliflozin group and 15,8% in control group. There were no differences in patients with HF from those with reduced ejection fraction and preserved. Conclusions Canagliflozin therapy at discharge was associated with a significant reduction in NT-ProBNP concentration in patients with diabetes after hospitalization for HF. FUNDunding Acknowledgement Type of funding sources: None. NT-ProBNP according to canagliflozin


EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
T Rudenko ◽  
O V Bilchenko ◽  
M O Khvysiuk ◽  
D Y Karami Saliba

Abstract Background Myocardial dyssynchrony  leads to heart remodeling and the progression of heart failure (HF) in patients with type 2 diabetes mellitus. Studying the mechanisms of the development of myocardial dyssynchrony can help in timely diagnosis and treatment. Aims To study the association of the level of galectin-3 and matrix metalloproteinase 1 (MMP-1) and the type of myocardial dyssynchrony in patients with heart failure and concomitant type 2 diabetes mellitus. Methods 98 patients with heart failure and concomitant type 2 diabetes mellitus were examined, average age (67.45 + 10.32) years. Patients were divided into two groups due to the presence or absence of myocardial dyssynchrony: the first group: with myocardial dyssynchrony (n = 56), the second group: patients without myocardial dyssynchrony ( n = 42). All patients were examined for electrical (enhanced QRS ≥ 120 ms) and mechanical myocardial dyssynchrony using echocardiographic and electrocardiographic methods for assessing intraventricular, interventricular, atrioventricular and combined myocardial dyssynchrony, as well as serum concentration of fibrosis markers - galectin-3 and MMP-1. The determination of percentage of interstitial collagen volume fraction (CVF) was performed in both groups. Results To determine the levels of fibrosis markers depending on the presence of diabetes, the results of patients with myocardial dyssynchrony (n = 56) were compared with the results of the control group without myocardial dyssynchrony (n = 42). In patients with myocardial dyssynchrony, there was an increase in the levels of galectin-3 (7.49 + 0.6 ng / ml) and CVF (7.6 ± 4.03%), a decrease in MMP-1 (0.46 + 0.2 ng / ml ) compared with the group without myocardial dyssynchrony (p &lt;0.05). An increase in galectin-3 levels was observed in the presence of combined forms of myocardial dyssynchrony. In patients with a combination of intraventricular, interventricular, or atrioventricular myocardial dyssynchrony (n = 28), the levels of galectin-3 (9.03 + 0.3 ng / ml) and CVF (8.04 + 1.6%) were the highest; in patients with isolated forms of myocardial dyssynchrony, the levels of galectin-3 (6.67 + 0.2 ng / ml) and CVF (6,93 + 1,4%) were significantly lower. MMP-1 was greater in patients with isolated forms of myocardial dyssynchrony (0.78 + 0.2 ng / ml), compared with patients with combined forms of myocardial dyssynchrony (0.2 + 0.01 ng / ml) (p &lt;0.05 ). Conclusions An association is observed between myocardial dyssynchrony and the levels of galectin-3 and MMP-1 in the blood. These findings are important for prognostic implications and require further research.


Diagnostics ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1577
Author(s):  
Raluca D. Ianoș ◽  
Călin Pop ◽  
Mihaela Iancu ◽  
Rodica Rahaian ◽  
Angela Cozma ◽  
...  

More than half of the patients with heart failure have preserved ejection fraction (HFpEF), however evidence shows a mortality rate comparable to those with reduced ejection fraction. The aim of this study was to evaluate whether FGF21, galectin-3 and copeptin can be used as biomarkers to identify HFpEF in patients with confirmed type 2 diabetes mellitus (DM). Sixty-nine diabetic patients were enrolled and divided into two groups: patients with HFpEF (n = 40) and those without HFpEF (n = 29). The ability of the studied biomarkers to discriminate HFpEF cases from non-HFpEF subjects were evaluated by the area under the Receiver Operating Characteristics (ROC) curve and the 95% confidence interval (CI). Compared to patients without heart failure, those with HFpEF had significantly higher levels of FGF21 (mean 146.79 pg/mL vs. 298.98 pg/mL). The AUC value of FGF21 was 0.88, 95% CI: [0.80, 0.96], Se = 85% [70.2, 94.3], Sp = 79.3% [60.3, 92.0], at an optimal cut-off value of 217.40 pg/mL. There was no statistical significance associated with galectin-3 and copeptin between patient cohorts. In conclusion, galectin-3 and copeptin levels were not effective for detecting HFpEF, while FGF21 is a promising biomarker for diagnosing HFpEF in DM patients.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Lorenzo-Almoros ◽  
A Pello ◽  
A Acena ◽  
J Martinez-Milla ◽  
N Tarin ◽  
...  

Abstract Introduction Type-2 diabetes mellitus (T2DM) is associated with early and severe atherosclerosis. However, few biomarkers can predict cardiovascular events in this population. Methods We followed 964 patients with coronary artery disease (CAD), assessing at baseline galectin-3, monocyte chemoattractant protein-1 (MCP-1) and N-terminal fragment of brain natriuretic peptide (NT-proBNP) plasma levels. Secondary outcomes were acute ischemia and heart failure or death. Primary outcome was the combination of the secondary outcomes. Results Male patients were 75.0% in T2DM and 76.6% in the non-T2DM subgroup (p=0.609). Age was 61.0 (54–72) and 60.0 (51–71) years, respectively (p=0.092). 232 patients had T2DM. Patients with T2DM showed higher MCP-1 [144 (113–195) vs. 133 (105–173) pg/ml, p=0.006] and galectin-3 [8.3 (6.5–10.5) vs. 7.8 (5.9–9.8) ng/ml, p=0.049] levels. Median follow-up was 5.39 years (2.81- 6.92). Galectin-3 levels were associated with increased risk of the primary outcome in T2DM patients [HR 1.57 (1.07–2.30); p=0.022], along with a history of cerebrovascular events. Treatment with clopidogrel was associated with lower risk. In contrast, NT-proBNP and MCP-1, but not galectin-3, were related to increased risk of the event in non-diabetic patients [HR 1.21 (1.04–1.42); p=0.017 and HR 1.23 (1.05–1.44); p=0.012, respectively], along with male sex and age. Galectin-3 was also the only biomarker that predicted the development of acute ischemic events and heart failure or death in T2DM patients, while in non-diabetics MCP-1 and NT-proBNP, respectively, predicted these events. Conclusion In CAD patients, cardiovascular events are predicted by galectin-3 plasma levels in patients with T2DM, and by MCP-1 and NT-proBNP in those without T2DM. Effect of Gal-3 on the primary endpoint Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Insituto de Salud Carlos III


Author(s):  
М.А. Быковская ◽  
А.А. Раскуражев ◽  
А.А. Шабалина ◽  
К.В. Антонова ◽  
М.М. Танашян

Введение. Сосудистые осложнения сахарного диабета (СД) являются одной из ведущих причин повышения смертности пациентов трудоспособного возраста. Предполагается, что индуцированный гипергликемией окислительный стресс и нарушение антиоксидантной защиты играют роль в патологическом механизме повреждения сосудов, частично за счет влияния оксида азота (NО). Цель исследования: уточнение взаимосвязей в системах асимметричного диметиларгинина (АДМА) и NO у пациентов с цереброваскулярными заболеваниями (ЦВЗ) на фоне СД 2-го типа (СД-2). Материалы и методы. Обследованы 72 пациента с ЦВЗ со стенозирующим поражением внутренней сонной артерии вне острого периода: группу 1 составили 39 пациентов (18 мужчин и 21 женщина) с СД-2 в возрасте 65 [58; 72] лет; в группу 2 вошли 33 больных (15 мужчин и 18 женщин) без СД-2 в возрасте 66 [56; 74] лет. Контрольную группу составили 30 добровольцев (16 мужчин и 14 женщин) без проявлений церебральной ишемии и нарушений углеводного обмена, с нормальными значениями индекса массы тела, некурящие, в возрасте 62 [50; 66] лет. Проводилось клиническое обследование, нейро- и ангиовизуализационное исследование, спектр биохимических исследований крови, в том числе определение содержания АДМА и показателей системы NO. Результаты. В группе 1 содержание нитрата, нитрита и NO составило 62,1 [56; 68] мкмоль/л, 48,5 [26; 52] мкмоль/л и 13,6 [9; 23] мкмоль/л соответственно, что достоверно отличалось от значений этих показателей в группе 2 — 58,3 [45; 64] мкмоль/л, 39,6 [26,0; 42,3] мкмоль/л и 18,7 [16,1; 24,7] мкмоль/л соответственно. Отмечен также более высокий уровень AДМА в крови у пациентов с ЦВЗ в сочетании с СД-2 — 0,42 [0,21; 0,53] ммоль/л. Заключение. Обнаружена взаимосвязь между уровнями AДМА и NO при ЦВЗ на фоне СД-2. Это требует продолжения исследований биомаркеров повреждения сосудистой стенки для определения их места в патогенезе ишемических церебральных осложнений СД-2. Background. Vascular complications of diabetes mellitus (DM) are one of the leading causes of increased mortality in patients of employable age. Hyperglycemia-induced oxidative stress and impaired antioxidant protection have been suggested to play a role in the pathological mechanism of vascular damage, in part due to the effects of nitric oxide (NO). Objectives: clarification of relationships in the systems of asymmetric dimethylarginine (ADMA) and NO in patients with cerebrovascular diseases (CVD) and type 2 diabetes (DM-2). Patients/Methods. We examined 72 CVD patients with stenosing lesions of the internal carotid artery outside the acute period: group 1 consisted of 39 patients (18 men and 21 women; 65 [58; 72] years old) with DM-2; group 2 consisted of 33 patients (15 men and 18 women; 66 [56; 74] years old) without DM-2. The control group consisted of 30 volunteers (16 men and 14 women; 62 [50; 66] years old) without manifestations of cerebral ischemia and carbohydrate metabolism disorders, with normal body mass index, non-smokers. A clinical examination, neuro- and angio-imaging study, a spectrum of biochemical blood tests, including the concentration of asymmetric dimethylarginine (ADMA) and indicators of NO system were carried out. Results. In group 1, the content of nitrate, nitrite and NO was 62.1 [56; 68] μmol/l, 48.5 [26; 52] μmol/l and 13.6 [9; 23] μmol/l, respectively, that significantly differed from the content of these parameters in group 2 — 58.3 [45; 64] μmol/l, 39.6 [26.0; 42.3] μmol/l and 18.7 [16.1; 24.7] μmol/l, respectively. Noted also a higher blood level of ADMA in patients with CVD combined with DM-2 — 0.42 [0.21; 0.53] mmol/l. Conclusions. A relationship was found between ADMA and NO levels in CVD patients with DM-2. This requires further studies of biomarkers of vascular wall damage to determine their place in the pathogenesis of ischemic cerebral complications of DM-2.


Diabetes ◽  
2021 ◽  
Vol 70 (Supplement 1) ◽  
pp. 223-OR
Author(s):  
ANDREA LUK ◽  
XINGE ZHANG ◽  
ERIK FUNG ◽  
HONGJIANG WU ◽  
ERIC S. LAU ◽  
...  

2021 ◽  
Vol 22 (1) ◽  
pp. 60-71
Author(s):  
I.A. Lapik ◽  
◽  
K.M. Gapparova ◽  
A.V. Galchenko ◽  
◽  
...  

Low caloric diet is used in the complex treatment of patients with diabetes mellitus and obesity. However, the reduced caloric food can inadvertently lead to decreased intake of micronutrients. The main goal of the research was to assess the necessity and effectiveness of the vitamin-mineral complex in the treatment of type 2 diabetes with obesity. Methods: 80 females suffering from type 2 diabetes and obesity, ranging from 40 to 65 years old participated in the study. The total patients were divided into two groups, each containing 40 patients. All patients were given a personalized diet and 1000mg of metformin every day. The experimental group, besides that, received vitamin-mineral complex. The biochemical analysis of the blood, composition of the body, and the complaint on micronutrient deficiency were taken before the experiment and after 14 days of the therapy. Results: Supplementation of the vitamin-mineral complex was associated with higher blood serum levels of vitamins B6, B12, B9, C, D, potassium, calcium, magnesium and zinc, and lower levels of glucose. Clinical manifestations, associated with micronutrient deficiency, were significantly decreased in patients who were given vitamin-mineral complex. All these changes were valid both in relation to the initial level in the study group and to the indicators after treatment in the control group. Conclusion: Micronutrient supplements may be a very important part of the combined therapy of patients with diabetes mellitus and obesity.


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