scholarly journals Association of Plasma Leucine-Rich α-2 Glycoprotein 1, a Modulator of Transforming Growth Factor-β Signaling Pathway, With Incident Heart Failure in Individuals With Type 2 Diabetes

2020 ◽  
Author(s):  
Jian-Jun Liu ◽  
Sharon LT Pek ◽  
Jiexun Wang ◽  
Sylvia Liu ◽  
Keven Ang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Transforming Growth Factor ◽  
Cox Regression ◽  
Transforming Growth Factor Β ◽  
Continuous Variable ◽  
Clinical Variable ◽  
Adjusted Risk ◽  
Increased Risk

<b>Objective: </b>Leucine-rich alpha-2 glycoprotein 1 (LRG1) is a circulating protein which potentially involves in several pathways related with pathogenesis of heart failure (HF). We aim to study whether plasma LRG1 is associated with risk of incident HF and hospitalization attributable to HF (HHF) in individuals with type 2 diabetes. <p><b>Design and Methods</b>: 1978 individuals with type 2 diabetes were followed for a median of 7.1 (IQR 6.1-7.6) years. Association of LRG1 with HF was studied by cause-specific Cox regression models. </p> <p><b>Results</b>: 191 incident HF and 119 HHF events were identified in follow-up. As compared to quartile 1, participants with LRG1 in quartile 3 and 4 had 3.60 (95% CI 1.63- 7.99) and 5.99 (95% CI 2.21-16.20) folds increased risk for incident HF, and 5.88 (95% CI 1.83-18.85) and 10.44 (95% CI 2.37- 45.98) folds increased risk for HHF after adjustment for multiple known cardio-renal risk factors. As a continuous variable, 1- SD increment in natural log-transformed LRG1 was associated with 1.78 (95% CI 1.33-2.38) folds adjusted risk for incident HF and 1.92 (95% CI 1.27- 2.92) folds adjusted risk for HHF. Adding LRG1 onto clinical variable- based model improved risk discrimination for incident HF (AUC 0.79 to 0.81, P=0.02) and HHF (AUC 0.81 to 0.84, P=0.02).</p> <p><b>Conclusion</b>: Plasma LRG1 is associated with risk of incident HF and HHF, suggesting that it may potentially involve in pathogenesis of HF in individuals with type 2 diabetes. Further studies are warranted to determine whether LRG1 may be a novel biomarker for HF risk-stratification.</p>

scholarly journals Association of Plasma Leucine-Rich α-2 Glycoprotein 1, a Modulator of Transforming Growth Factor-β Signaling Pathway, With Incident Heart Failure in Individuals With Type 2 Diabetes

2020 ◽  
Author(s):  
Jian-Jun Liu ◽  
Sharon LT Pek ◽  
Jiexun Wang ◽  
Sylvia Liu ◽  
Keven Ang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Transforming Growth Factor ◽  
Cox Regression ◽  
Transforming Growth Factor Β ◽  
Continuous Variable ◽  
Clinical Variable ◽  
Adjusted Risk ◽  
Increased Risk

<b>Objective: </b>Leucine-rich alpha-2 glycoprotein 1 (LRG1) is a circulating protein which potentially involves in several pathways related with pathogenesis of heart failure (HF). We aim to study whether plasma LRG1 is associated with risk of incident HF and hospitalization attributable to HF (HHF) in individuals with type 2 diabetes. <p><b>Design and Methods</b>: 1978 individuals with type 2 diabetes were followed for a median of 7.1 (IQR 6.1-7.6) years. Association of LRG1 with HF was studied by cause-specific Cox regression models. </p> <p><b>Results</b>: 191 incident HF and 119 HHF events were identified in follow-up. As compared to quartile 1, participants with LRG1 in quartile 3 and 4 had 3.60 (95% CI 1.63- 7.99) and 5.99 (95% CI 2.21-16.20) folds increased risk for incident HF, and 5.88 (95% CI 1.83-18.85) and 10.44 (95% CI 2.37- 45.98) folds increased risk for HHF after adjustment for multiple known cardio-renal risk factors. As a continuous variable, 1- SD increment in natural log-transformed LRG1 was associated with 1.78 (95% CI 1.33-2.38) folds adjusted risk for incident HF and 1.92 (95% CI 1.27- 2.92) folds adjusted risk for HHF. Adding LRG1 onto clinical variable- based model improved risk discrimination for incident HF (AUC 0.79 to 0.81, P=0.02) and HHF (AUC 0.81 to 0.84, P=0.02).</p> <p><b>Conclusion</b>: Plasma LRG1 is associated with risk of incident HF and HHF, suggesting that it may potentially involve in pathogenesis of HF in individuals with type 2 diabetes. Further studies are warranted to determine whether LRG1 may be a novel biomarker for HF risk-stratification.</p>

scholarly journals MR-proANP and incident cardiovascular disease in patients with type 2 diabetes with and without heart failure with preserved ejection fraction

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Jesper Jensen ◽  
Morten Schou ◽  
Caroline Kistorp ◽  
Jens Faber ◽  
Tine W. Hansen ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Ejection Fraction ◽  
Natriuretic Peptides ◽  
Continuous Variable ◽  
Preserved Ejection Fraction ◽  
Reduced Ejection Fraction ◽  
Increased Risk ◽  
Definition Of

Abstract Background Mid-regional pro-atrial natriuretic peptide (MR-proANP) is a useful biomarker in outpatients with type 2 diabetes (T2D) to diagnose heart failure (HF). Elevated B-type natriuretic peptides are included in the definition of HF with preserved ejection fraction (HFpEF) but little is known about the prognostic value of including A-type natriuretic peptides (MR-proANP) in the evaluation of patients with T2D. Methods We prospectively evaluated the risk of incident cardiovascular (CV) events in outpatients with T2D (n = 806, mean ± standard deviation age 64 ± 10 years, 65% male, median [interquartile range] duration of diabetes 12 [6–17] years, 17.5% with symptomatic HFpEF) according to MR-proANP levels and stratified according to HF-status including further stratification according to a prespecified cut-off level of MR-proANP. Results A total of 126 CV events occurred (median follow-up 4.8 [4.1–5.3] years). An elevated MR-proANP, with a cut-off of 60 pmol/l or as a continuous variable, was associated with incident CV events (p < 0.001). Compared to patients without HF, patients with HFpEF and high MR-proANP (≥ 60 pmol/l; median 124 [89–202] pmol/l) and patients with HF and reduced ejection fraction (HFrEF) had a higher risk of CV events (multivariable model; hazard ratio (HR) 2.56 [95% CI 1.64–4.00] and 3.32 [1.64–6.74], respectively). Conversely, patients with HFpEF and low MR-proANP (< 60 pmol/l; median 46 [32–56] pmol/l) did not have an increased risk (HR 2.18 [0.78–6.14]). Conclusions Patients with T2D and HFpEF with high MR-proANP levels had an increased risk for CV events compared to patients with HFpEF without elevated MR-proANP and compared to patients without HF, supporting the use of MR-proANP in the definition of HFpEF from a prognostic point-of-view.

P2629Early benefits of empagliflozin in patients with type 2 diabetes with heart failure are not offset by increased adverse events: results from the EMPA-REG OUTCOME trial

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P Pellicori ◽  
A Pernille Ofstad ◽  
D Fitchett ◽  
C Zeller ◽  
C Wanner ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Adverse Events ◽  
Repeated Measures ◽  
Cox Regression ◽  
Sglt2 Inhibitor ◽  
Safety Data ◽  
Increased Risk ◽  
Outcome Trial

Abstract Background The cardiovascular (CV) benefits of sodium-glucose co-transporter-2 (SGLT2) inhibitors in patients with type 2 diabetes (T2D) have been demonstrated in long-term clinical trials. In the EMPA-REG OUTCOME trial, the SGLT2 inhibitor empagliflozin (EMPA), compared with placebo (PBO), significantly reduced the risk of CV death and hospitalisation for heart failure (HHF) in patients with T2D and established CV disease, with a median follow-up time of 3.1 years. Purpose To investigate the early benefits and safety associated with use of EMPA in patients enrolled in the EMPA-REG OUTCOME trial according to heart failure (HF) status at baseline. Methods We evaluated the effects of treatments on glycated haemoglobin (HbA1c) levels and on the clinical endpoints of HHF, HHF or CV death, and HHF or all-cause mortality (ACM), as well as the occurrence of adverse events (AEs), at 12 weeks, 6 months, and 1 year after randomisation. Outcomes data were explored descriptively at 12 weeks, and assessed by Cox regression models adjusting for baseline risk factors at 6 months, and 1 year, whereas safety data were explored descriptively. Effects on HbA1c were evaluated using a Mixed Model Repeated Measures (MMRM) model. Results A total of 7020 participants, 706 (10%) with investigator-reported HF at baseline, were randomised to PBO, or two different doses of EMPA (10 mg or 25 mg once daily). In patients with HF at baseline, the adjusted mean differences in HbA1c between pooled EMPA and PBO at 12 weeks, 6 months, and 1 year after randomisation were −0.55, −0.54 and −0.53%-point, respectively, p<0.001 vs PBO for all, with similar results in those without HF (p for interactions 0.822, 0.939 and 0.539 at 12 weeks, 6 months and 1 year, respectively). Already at 12 weeks, patients assigned to EMPA had a lower frequency of all evaluated clinical outcome events (HHF, HHF or CV death, HHF or ACM) compared with PBO, regardless of HF status. This effect was sustained and significant at 6 months and 1 year in those with and without HF (see Figure). During the same time frame, the rates of AEs were generally higher in those with HF than without HF, but were not increased by the use of EMPA. At 1 year, any AE occurred in 206 (84.4%) and 1694 (81.1%) patients with and without HF, respectively, on PBO vs 363 (78.6%) and 3246 (76.8%) patients with and without HF on EMPA; any serious AE at 1 year occurred in 79 (32.4%) and 447 (21.4%) patients with and without HF on PBO vs 105 (22.7%) and 764 (18.1%) of those with and without HF on EMPA. Conclusions In the EMPA-REG OUTCOME trial, EMPA led to early beneficial effects on morbidity and mortality outcomes in patients with T2D with or without HF, which were not offset by an increased risk of AEs.

scholarly journals Circulating Trimethylamine N-Oxide Is Associated with Increased Risk of Cardiovascular Mortality in Type-2 Diabetes: Results from a Dutch Diabetes Cohort (ZODIAC-59)

2021 ◽  
Vol 10 (11) ◽  
pp. 2269
Author(s):  
Jose L. Flores-Guerrero ◽  
Peter R. van Dijk ◽  
Margery A. Connelly ◽  
Erwin Garcia ◽  
Henk J. G. Bilo ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Mortality Risk ◽  
Cox Regression ◽  
Plasma Concentrations ◽  
Continuous Variable ◽  
Resonance Spectroscopy ◽  
Increased Risk ◽  
Branched Chain ◽  
Cv Disease

Trimethylamine N-oxide (TMAO), a novel cardiovascular (CV) disease and mortality risk marker, is a gut microbiota-derived metabolite as well. Recently, plasma concentrations of branched-chain amino acids (BCAA) have been reported to be affected by microbiota. The association of plasma TMAO with CV mortality in Type 2 Diabetes (T2D) and its determinants are still incompletely described. We evaluated the association between plasma BCAA and TMAO, and the association of TMAO with CV mortality in T2D individuals. We used data of 595 participants (mean age 69.5 years) from the Zwolle Outpatient Diabetes project Integrating Available Care (ZODIAC) cohort were analyzed. Plasma TMAO and BCAA were measured with nuclear magnetic resonance spectroscopy. CV mortality risk was estimated using multivariable-adjusted Cox regression models. Cross-sectionally, TMAO was independently associated with BCAA standardized (Std) β = 0.18 (95% Confidence Interval (CI) 0.09; 0.27), p <0.001. During a median follow-up of 10 years, 113 CV deaths were recorded. In Cox regression analyses, adjusted for multiple clinical and laboratory variables including BCAA, TMAO was independently associated with CV mortality: adjusted hazard ratio (adjHR) 1.93 (95% CI 1.11; 3.34), p = 0.02 (for the highest vs. the lowest tertile of the TMAO distribution). The same was true for analyses with TMAO as continuous variable: adjHR 1.32 (95% CI 1.07; 1.63), p = 0.01 (per 1 SD increase). In contrast, BCAAs were not associated with increased CV mortality. In conclusion, higher plasma TMAO but not BCAA concentrations are associated with an increased risk of CV mortality in individuals with T2D, independent of clinical and biochemical risk markers.

New-onset type 2 diabetes in heart failure: impact of heart failure and death versus ischemic events – a Danish nationwide cohort study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
B Zareini ◽  
P.B Blanche ◽  
A.H Holt ◽  
M.M Malik ◽  
D.P Rajan ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Risk Ratio ◽  
Real Life ◽  
Ischemic Event ◽  
Increased Risk ◽  
The Absolute ◽  
Ischemic Events ◽  
New Onset

Abstract Background Development of type 2 diabetes (T2D) is common in patients with heart failure (HF), but knowledge of future cardiovascular events is lacking. Purpose We compared risk of heart failure hospitalization (HFH) or death versus ischemic events in real-life HF patients with new-onset T2D, prevalent T2D and no T2D. Methods Using the Danish nationwide registers, we identified all patients with HF between 1998–2016. The patients were separated in two different HF cohorts based on the status of T2D. One cohort consisted of HF patients with either prevalent or absent T2D at the time of HF diagnosis. The other cohort consisted of HF patients, who developed new-onset T2D, included at time of diagnosis. The two HF cohorts were analyzed separately. Outcomes for both cohorts were analyzed as time-to-first event as either an ischemic event (i.e. composite outcome of fatal and non-fatal myocardial infarction, stroke, and peripheral artery disease), HFH, or event-free death (not related to HFH or the ischemic event). For each cohort, we estimated the five-year absolute risk of ischemic event, HFH and event-free death, along with five-year risk ratio of HFH or event-free death versus ischemic events. Effects among subgroups were investigated by stratifying both cohorts based on age, gender and comorbidities present at inclusion. Results A total of 139,264 HF patients were included between 1998 and 2016, of which 29,078 (21%) patients had prevalent T2D at baseline. A total of 11,819 (8%) developed new-onset T2D and were included in the second cohort. The median duration of time between HF diagnosis and new-onset T2D diagnosis was: 4.1 years (IQR:1.5; 5.8). The absolute five-year risk of an ischemic event in patients with new-onset T2D, prevalent T2D and no T2D was: 17.9% (95% confidence interval (CI): 17.2; 18.6), 26.1% (95% CI: 25.6; 26.7), and 18.8% (95% CI:18.6; 19.0). Corresponding estimates for HFH were: 31.5% (95% CI: 30.6; 32.3), 33.6% (95% CI: 33.0; 34.2), and 30,7% (95% CI: 30.5; 31.0). The absolute five-year risk of event-free death among patients with new-onset T2D, prevalent T2D and no T2D was: 20.9% (95% CI: 20.2; 21.7), 18.9% (95% CI:18.4; 19.3), and 18.6% (95% CI: 18.4; 18.8) (see Figure). The five-year risk ratio of experiencing HFH or event-free death versus an ischemic event was: 2.9 (95% CI: 2.8; 3.1), 2.0 (95% CI:2.0; 2.1), and 2.6 (95% CI: 2.6; 2.7) for patients with new-onset T2D, prevalent T2D and no T2D, respectively. Similar results of absolute and relative risk were present across all subgroups. Conclusion In our population of HF patients, 8% developed new-onset diabetes. Development of T2D in patients with HF increases the risk of HFH and mortality three-fold. The increased risk of new-onset T2D is higher than the importance of prevalent T2D in patients with HF. Funding Acknowledgement Type of funding source: None

Galectin-3 predicts cardiovascular events in patients with type-2 diabetes

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Lorenzo-Almoros ◽  
A Pello ◽  
A Acena ◽  
J Martinez-Milla ◽  
N Tarin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Type 2 Diabetes ◽  
Plasma Levels ◽  
Cardiovascular Events ◽  
Primary Outcome ◽  
Funding Source ◽  
Increased Risk ◽  
Galectin 3 ◽  
Secondary Outcomes

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

Myopia and Early Onset Type 2 Diabetes: A Nationwide Cohort Study

2021 ◽  
Author(s):  
Alon Peled ◽  
Itamar Raz ◽  
Inbar Zucker ◽  
Estela Derazne ◽  
Jacob Megreli ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cohort Study ◽  
Young Adulthood ◽  
Military Service ◽  
High Myopia ◽  
Continuous Variable ◽  
Dependent Manner ◽  
Increased Risk

Abstract Objective A correlation between myopia and insulin-resistance has been suggested. We investigated the association between myopia in adolescence and type 2 diabetes (T2D) incidence in young adulthood. Design Population-based, retrospective, cohort study. Methods 1,329,705 adolescents (579,543 women, 43.6%) aged 16-19 years, medically examined before mandatory military service during 1993-2012; and whose data were linked to the Israel National Diabetes Registry. Myopia was defined based on right eye refractive data. Cox proportional models were applied, separately for women and men, to estimate hazard ratios (HRs) for T2D incidence per person-years of follow-up. Results There was an interaction between myopia and sex with T2D (P&lt;0.001). For women, T2D incidence rates (per 100,000 person-years) were 16.6, 19.2, and 25.1 for those without myopia, and with mild-to-moderate and high myopia, respectively. These corresponded to HRs of 1.29 (95%CI 1.14-1.45) and 1.63 (1.21-2.18) for women with mild-to-moderate and high myopia, respectively, compared to those without myopia, after adjustment for age at study entry, birth year, adolescent BMI, cognitive performance, socioeconomic status, and immigration status. Results persisted in extensive sensitivity and subgroup analyses. When managed as a continuous variable, every 1 diopter lower spherical equivalent yielded a 6.5% higher adjusted HR for T2D incidence (P= 0.003). There was no significant association among men. Conclusions For women, myopia in adolescence was associated with a significantly increased risk for incident T2D in young adulthood, in a severity-dependent manner. This finding may support the role of insulin resistance in myopia pathogenesis.

scholarly journals Correlation between markers of renal function and sight-threatening diabetic retinopathy in type 2 diabetes: a longitudinal study in an Indian clinic population

2020 ◽  
Vol 8 (1) ◽  
pp. e001325 ◽  
Author(s):  
Ramachandran Rajalakshmi ◽  
Coimbatore Subramanian Shanthi Rani ◽  
Ulagamathesan Venkatesan ◽  
Ranjit Unnikrishnan ◽  
Ranjit Mohan Anjana ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Retinopathy ◽  
Serum Creatinine ◽  
Cox Regression ◽  
Tertiary Care ◽  
Cox Regression Analysis ◽  
Increased Risk ◽  
New Onset

IntroductionPrevious epidemiological studies have reported on the prevalence of diabetic kidney disease (DKD) and diabetic retinopathy (DR) from India. The aim of this study is to evaluate the effect of DKD on the development of new-onset DR and sight-threatening diabetic retinopathy (STDR) in Asian Indians with type 2 diabetes (T2D).Research design and methodsThe study was done on anonymized electronic medical record data of people with T2D who had undergone screening for DR and renal work-up as part of routine follow-up at a tertiary care diabetes center in Chennai, South India. The baseline data retrieved included clinical and biochemical parameters including renal profiles (serum creatinine, estimated glomerular filtration rate (eGFR) and albuminuria). Grading of DR was performed using the modified Early Treatment Diabetic Retinopathy Study grading system. STDR was defined as the presence of proliferative diabetic retinopathy (PDR) and/or diabetic macular edema. DKD was defined by the presence of albuminuria (≥30 µg/mg) and/or reduction in eGFR (<60 mL/min/1.73 m2). Cox regression analysis was used to evaluate the hazard ratio (HR) for DR and STDR.ResultsData of 19 909 individuals with T2D (mean age 59.6±10.2 years, mean duration of diabetes 11.1±12.1 years, 66.1% male) were analyzed. At baseline, DR was present in 7818 individuals (39.3%), of whom 2249 (11.3%) had STDR. During the mean follow-up period of 3.9±1.9 years, 2140 (17.7%) developed new-onset DR and 980 individuals with non-proliferative DR (NPDR) at baseline progressed to STDR. Higher serum creatinine (HR 1.5, 95% CI 1.3 to 1.7; p<0.0001), eGFR <30 mL/min/1.73 m2 (HR 4.9, 95% CI 2.9 to 8.2; p<0.0001) and presence of macroalbuminuria >300 µg/mg (HR 3.0, 95% CI 2.4 to 3.8; p<0.0001) at baseline were associated with increased risk of progression to STDR.ConclusionsDKD at baseline is a risk factor for progression to STDR. Physicians should promptly refer their patients with DKD to ophthalmologists for timely detection and management of STDR.

Sign in / Sign up

Export Citation Format

Share Document