scholarly journals Linagliptin Effects on Heart Failure and Related Outcomes in Individuals With Type 2 Diabetes Mellitus at High Cardiovascular and Renal Risk in CARMELINA

Circulation ◽  
2019 ◽  
Vol 139 (3) ◽  
pp. 351-361 ◽  
Author(s):  
Darren K. McGuire ◽  
John H. Alexander ◽  
Odd Erik Johansen ◽  
Vlado Perkovic ◽  
Julio Rosenstock ◽  
...  

Background: Individuals with type 2 diabetes mellitus are at increased risk for heart failure (HF), particularly those with coexisting atherosclerotic cardiovascular disease and/or kidney disease. Some but not all dipeptidyl peptidase-4 inhibitors have been associated with increased HF risk. We performed secondary analyses of HF and related outcomes with the dipeptidyl peptidase-4 inhibitor linagliptin versus placebo in CARMELINA (The Cardiovascular and Renal Microvascular Outcome Study With Linagliptin), a cardiovascular outcomes trial that enrolled participants with type 2 diabetes mellitus and atherosclerotic cardiovascular disease and/or kidney disease. Methods: Participants in 27 countries with type 2 diabetes mellitus and concomitant atherosclerotic cardiovascular disease and/or kidney disease were randomized 1:1 to receive once daily oral linagliptin 5 mg or placebo, on top of standard of care. All hospitalization for HF (hHF), cardiovascular outcomes, and deaths were prospectively captured and centrally adjudicated. In prespecified and post hoc analyses of HF and related events, Cox proportional hazards models adjusting for region and baseline history of HF were used. Recurrent hHF events were analyzed using a negative binomial model. In a subset of participants with left ventricular ejection fraction captured within the year before randomization, HF-related outcomes were assessed in subgroups stratified by left ventricular ejection fraction > or ≤50%. Results: CARMELINA enrolled 6979 participants (mean age, 65.9 years; estimated glomerular filtration rate, mL/min per 1.73m 2 ; hemoglobin A1c, 8.0%; 62.9% men; diabetes mellitus duration, 14.8 years), including 1873 (26.8%) with a history of HF at baseline. Median follow-up was 2.2 years. Linagliptin versus placebo did not affect the incidence of hHF (209/3494 [6.0%] versus 226/3485 [6.5%], respectively; hazard ratio [HR], 0.90; 95% CI, 0.74–1.08), the composite of cardiovascular death/hHF (HR, 0.94; 95% CI, 0.82–1.08), or risk for recurrent hHF events (326 versus 359 events, respectively; rate ratio, 0.94; 95% CI, 0.75–1.20). There was no heterogeneity of linagliptin effects on hHF by history of HF at baseline, baseline estimated glomerular filtration rate or urine albumin-creatinine ratio, or prerandomization left ventricular ejection fraction. Conclusions: In a large, international cardiovascular outcome trial in participants with type 2 diabetes mellitus and concomitant atherosclerotic cardiovascular disease and/or kidney disease, linagliptin did not affect the risk of hHF or other selected HF-related outcomes, including among participants with and without a history of HF, across the spectrum of kidney disease, and independent of previous left ventricular ejection fraction. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01897532.

2015 ◽  
Vol 61 (2) ◽  
pp. 21-27
Author(s):  
I P Tatarchenko ◽  
N V Pozdnyakova ◽  
A G Denisova ◽  
O I Morozova

The present study was focused on the assessment of electrophysiological, structural, and functional characteristics of the heart associated with ventricular rhythm disturbances in the patients with type 2 diabetes mellitus (DM2) suffering from diastolic cardiac insufficiency. The study involved a total of 128 patients with DM2 and coronary heart disease (CHD) exhibiting signs of functional class I-III chronic cardiac insufficiency and left ventricular ejection fraction over 50%. The patients were divided into three groups. Group 1 (n=55) included patients presenting with left ventricular relaxation. Group 2 (n=44) was comprised of the patients with the pseudo-normal type of diastolic dysfunction. Group 3 (n=29) consisted of the patients with restrictive diastolic dysfunction. The patients of the latter group were characterized by the high frequency of complicated forms of ventricular arrhythmia, such as Grade IV-V ventricular extrasystole (48.3%) and Grade III ventricular extrasystole (34.5%). Restrictive type of diastolic dysfunction was associated with the delayed fragmented activity in the end part of the ventricular complex in 72.4% of the patients. The close correlation between the left ventricular diastolic function and parameters of myocardial electrical remodeling was documented.


2020 ◽  
Vol 27 (5) ◽  
pp. 60-70
Author(s):  
L. G. Voronkov ◽  
N. A. Tkach ◽  
O. L. Filatova ◽  
T. I. Gavrilenko ◽  
G. Ye. Dudnik ◽  
...  

The aim – to compare clinical and instrumental parameters and cumulative survival of women and men with chronic heart failure (CHF) and reduced left ventricular ejection fraction (LV EF), depending on the presence of type II diabetes mellitus.Materials and methods. A retrospective analysis of 490 case histories of patients observed in the heart failure department in the period from 2011 to 2018, with CHF, II–IV NYHA functional class, LVEF ≤ 40 %, 40–80 years of age (median (quartiles)) – 64 (56.00; 69.00) years). The study group included mainly patients with coronary heart disease in combination with hypertension – 403 (82.2 %) patients, with isolated coronary heart disease – 55 (11.2 %) and with isolated hypertension – 32 (6.6 %). Most patients (278 (56.7 %)) had a permanent form of atrial fibrillation. Among the subjects were 373 (76.1 %) men and 117 (23.9 %) women. Comparisons were performed in populations of men and women depending on the presence of type 2 diabetes. Patients were included in the study in the phase of clinical compensation, in the euvolemic state.Results and discussion. The analysis revealed that the prevalence of type 2 diabetes mellitus in the population of men with CHF and reduced LV EF is significantly lower than in the female population. There were no significant differences between the study groups by etiology, the NYHA class, as well as the structure of comorbid conditions. Also there were no significant differences in age, mean daily heart rate, systolic and diastolic blood pressure. Despite expectations, insulin levels in both male and female cohorts did not differ significantly in patients with and without concomitant diabetes. In the cohort of men with CHF and reduced LV EF with concomitant diabetes the body mass index, anteroposterior left atrial size, GFR values were significantly higher, whereas the level of circulating citrulline and urea nitrogen were significantly lower compared to women. Women with CHF with reduced LV EF and concomitant diabetes compared to women without diabetes had lower LV EF and left atrial size, higher circulating citrulline levels, and E/е´ ratios. Analysis of the kidneys functional state showed deterioration of nitrogen excretory function in all study groups in the presence of type 2 diabetes mellitus. The five-year survival of men with CHF and reduced LV EF did not differ depending on the presence of type 2 diabetes mellitus. Instead, when analyzing the effect of type 2 diabetes mellitus on life expectancy in women with CHF and reduced LV EF, we observed a significantly worse prognosis.Conclusions. Woman with CHF and reduced LV EF with concomitant type 2 diabetes mellitus is characterized by a worse clinical course of the disease, which is combined with signs of more pronounced damage to target organs (heart, kidneys). At the same time, in women with diabetes, compared with men, the nitrogen-excreting renal function is significantly lower. Cumulative 5-year survival in the male cohort depending on presence of diabetes did not differ, while women with diabetes were characterized by significantly lower 5-year survival compared to women without diabetes.


2019 ◽  
Vol 8 ◽  
Author(s):  
Andrea Muñoz Lara ◽  
Jorge García Vega ◽  
Juan Pablo Moncada Patiño ◽  
Alma Rosa Tovar ◽  
Patricia Isolina del Socorro Gómez Aguilar

Introduction: The complications of type 2 diabetes mellitus (T2DM), such as chronic kidney disease (CKD), are the second leading cause of death in Oxcutzcab municipality of Yacatan, Mexico. The objective of the study was to estimate the burden of chronic kidney disease in a sample of patients with T2DM from Oxcutzcab municipality of Yacatan, Mexico, region characterized by high amound of poverty and vulnerabidity.Methods: This is a descriptive study involving 108 adult patients between 26 and 79 years old with T2DM who attended the PROSPERA, social protection program under the direction of Ministry of Social Development of Mexico (88% female and 12% male). Weight, height, BMI, and years of post T2DM diagnosis were measured. Estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault formula. Results: We found that 39.81% of participants had stage one kidney damage, 34.26% stage two, 24.07% stage three, one case of stage four, and one of stage five. BMI measurements indicated that 40.74% of participants were obese (≥30kg/m2), 35.19% were overweight, and 1.85% were underweight. In terms of years since diagnosis, 37.04% of the participants were diagnosed five years ago and less, 29.63% of participants were diagnosed 6-10 years ago, 22.22% between 11-15 years ago, 8.33% between 16-20 years ago, and 2.78% of participants over 20 years ago.Conclusions: Most participants were in stages one to three of kidney damage, where the main objective of the medical team was medical treatment of T2DM and comorbidities, as well as nutritional support to prevent further complications. There was only one case in stage four and five each, where dialysis and kidney transplantation became necessary. Both cases presented had a history of T2DM for over 20 years. It is important to identify early kidney damage to improve quality of life, reduce the treatment costs, and lower mortality.


2021 ◽  
Vol 4 (2) ◽  
Author(s):  
Tri Damayanti Simanjuntak ◽  
Tri Yunis Miko Wahyono

In 2010, the Global Burden of Disease research revealed that cases of chronic kidney disease had increased and became a serious health problem. Indonesia Basic Health Research data in 2013 revealed that the proportion of patients with chronic kidney failure aged ≥ 15 years old based on doctor's diagnosis was 0,2% and 0,6% kidney stones. Therefore the aim of the study is to analyze the relationship between type 2 diabetes mellitus and chronic kidney disease in the population of Indonesia in 2014-2015. This type of research is observational with a cross-sectional design. The study used secondary data from the Indonesia Family Life Survey (IFLS) 5 in 2014-2015. The sampling technique used total sampling, which found 34,012 people who met the inclusion and exclusion criteria. The independent variables of this study are type 2 diabetes mellitus and chronic kidney disease as the dependent variable. Covariate variables are age, sex, smoking status, history of hypertension, and history of high cholesterol. Analysis bivariate of the relationship between type 2 diabetes mellitus and chronic kidney disease in this study using chi square and multivariate analysis using logistic regression test. The magnitude of the effect expressed in the prevalence odds ratio (POR) with confident interval (CI: 95%.) This study shows the prevalence of chronic kidney disease in Indonesia population in 2014 – 2015 is 1%. The result of chi-square test of the relationship between type 2 diabetes mellitus and chronic kidney disease in the Indonesian population showed POR=2.48 (p-value =0.0002; 95%CI 1.422-4.071). Multivariate analysis with logistic regression tests shows that smoking status, history of high cholesterol, and history of hypertension influence the relationship of type 2 diabetes mellitus and chronic kidney disease.


2013 ◽  
Vol 16 (2) ◽  
pp. 17-25 ◽  
Author(s):  
Tatiana Nikolaevna Kochegura ◽  
P I Makarevich ◽  
A G Ovchinnikov ◽  
L V Zhigunova ◽  
Elena Leonidovna Lahova ◽  
...  

AIM: To evaluate the plasma level of circulating heptocyte growth factor (HGF) in patients with comorbidity of post-infarction chronic heart failure (CHF), type 2 diabetes mellitus (T2DM) and obesity. We also aimed to assess possible correlations between HGF levels and parameters of carbohydrate and lipid metabolism, as well as myocardial functional characteristics and classic biochemical severity markers for CHF.17Сахар ный диабет КардиологияСахарный диабет. 2013;(2):17-25 MATERIALS AND METHODS: We enrolled 100 patients for participation in this study, including the following subgroups: 20 individuals with- out cardiovascular and glycemic disorders, 30 patients with CHF, 25 patients with CHF/T2DM comorbidity and 25 diabetic patients with no signs of heart failure. Quantitative plasma HGF analysis was performed with enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma HGF was elevated both in patients with CHF and T2DM as measured against healthy control group. The elevation was most prominent in patients with CHF/T2DM comorbidity and was found to correlate with HbA1c level (r=0.52, p=0.03). Plasma HGF also correlated with BMI (r=0.42, p=0007) in a unified study group, though we observed no statistically significant difference between subgroups with a trend toward higher HGF in obese patients with CHF/T2DM comorbidity (626.1?254.1 pg/ml vs 742.0?210.7 pg/ml respectively; p 0.05). Interestingly, plasma HGF was also significantly higher in controls with BMI 30 km/m2 (324.1?107.7 pg/ml vs 436.9?112.3 pg/ml, p=0.03).Circulating HGF correlated with plasma levels of N-terminal fragment of B-type natriuretic peptide (NT-proBNP) and such structural and functional myocardial characteristics as left atrial size and maximum volume along with left ventricular ejection fraction (EF), end-diastolic volume (EDV) and end-diastolic dimension (EDD). CONCLUSION: These findings suggest that HGF may potentially serve as a prediction marker for unfavorable myocardial remodeling and poor prognosis in CHF patients with T2DM and obesity, though this possibility should be further investigated in follow-up studies.


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