scholarly journals Plasma COOH-Terminal Proendothelin-1: A marker of fatal cardiovascular events, all-cause mortality, and new-onset albuminuria in type 2 diabetes? (ZODIAC-29)

Diabetes Care ◽  
2012 ◽  
Vol 35 (11) ◽  
pp. 2354-2358 ◽  
Author(s):  
I. Drion ◽  
N. Kleefstra ◽  
G. W. D. Landman ◽  
A. Alkhalaf ◽  
J. Struck ◽  
...  
2021 ◽  
Author(s):  
Sharen Lee ◽  
Jiandong Zhou ◽  
Carlin Chang ◽  
Tong Liu ◽  
Dong Chang ◽  
...  

AbstractBackgroundSGLT2I and DPP4I are medications prescribed for type 2 diabetes mellitus patients. However, there are few population-based studies comparing their effects on incident atrial fibrillation or ischemic stroke.MethodsThis was a territory-wide cohort study of type 2 diabetes mellitus patients prescribed SGLT2I or DPP4I between January 1st, 2015 to December 31st, 2019 in Hong Kong. Patients with both DPP4I and SGLT2I use and patients with drug discontinuation were excluded. Patients with prior AF or stroke were excluded for the respective analysis. 1:2 propensity-score matching was conducted for demographics, past comorbidities and medications using nearest-neighbor matching method. Cox models were used to identify significant predictors for new onset heart failure (HF) or myocardial infarction (MI), cardiovascular and all-cause mortality.ResultsThe AF-free cohort included 49108 patients (mean age: 66.48 years old [SD: 12.89], 55.32% males) and the stroke-free cohort included 49563 patients (27244 males [54.96%], mean baseline age: 66.7 years old [SD: 12.97, max: 104.6 years old]). After propensity score matching, SGLT2i use was associated with a lower risk of new onset AF (HR: 0.43[0.28, 0.66]), cardiovascular mortality (HR: 0.79[0.58, 1.09]) and all-cause mortality (HR: 0.69[0.60, 0.79]) in the AF-free cohort. It was also associated with a lower risk of new onset stroke (0.46[0.33, 0.64]), cardiovascular mortality (HR: 0.74[0.55, 1.00]) and all-cause mortality (HR: 0.64[0.56, 0.74]) in the stroke-free cohort.ConclusionsThe novelty of our work si that SGLT2 inhibitors are protective against atrial fibrillation and stroke development for the first time. These findings should be validated in other cohorts.


2020 ◽  
Author(s):  
Anne Gedebjerg ◽  
Mette Bjerre ◽  
Alisa Devedzic Kjaergaard ◽  
Rudi Steffensen ◽  
Jens Steen Nielsen ◽  
...  

<b>Objective</b>: Mannose-binding lectin (MBL) is linked to risk of cardiovascular disease in diabetes, but the nature of the association is unclear. We investigated the association between MBL and risk of cardiovascular events (CVE) and all-cause mortality in type 2 diabetes. <p><b>Research Design and Methods</b>: In a cohort study of 7588 patients with type 2 diabetes, we measured serum MBL in 7305 and performed MBL expression genotyping in 3043. We grouped serum MBL and MBL expression genotypes into three categories: low, intermediate, and high. Outcomes were CVE (myocardial infarction, stroke, coronary revascularization, unstable angina, and cardiovascular death) and all-cause mortality. The association with outcomes was examined by spline and Cox regression analyses. </p> <p><b>Results</b>: Serum MBL and CVE showed a U-shaped association. Compared to the intermediate serum MBL category, the adjusted hazard ratio (HR) for CVE was 1.82 (95% CI, 1.34 to 2.46) for the low-MBL category and 1.48 (95% CI, 1.14 to 1.92) for the high-MBL category. We found a similar U-shaped association for all-cause mortality, but with lower risk estimates. Compared to the intermediate MBL expression genotype, the adjusted HR for CVE was 1.40 (95% CI, 0.87 to 2.25) for the low-expression genotype and 1.44 (95% CI, 1.01 to 2.06) for the high-expression genotype. MBL expression genotype was not associated with all-cause mortality. </p> <p><b>Conclusions:</b> Both serum MBL and MBL expression genotype showed a U-shaped association with CVE risk in individuals with type 2 diabetes. Our findings suggest that serum MBL is a risk factor for cardiovascular disease in this population.</p>


2020 ◽  
Author(s):  
Anne Gedebjerg ◽  
Mette Bjerre ◽  
Alisa Devedzic Kjaergaard ◽  
Rudi Steffensen ◽  
Jens Steen Nielsen ◽  
...  

<b>Objective</b>: Mannose-binding lectin (MBL) is linked to risk of cardiovascular disease in diabetes, but the nature of the association is unclear. We investigated the association between MBL and risk of cardiovascular events (CVE) and all-cause mortality in type 2 diabetes. <p><b>Research Design and Methods</b>: In a cohort study of 7588 patients with type 2 diabetes, we measured serum MBL in 7305 and performed MBL expression genotyping in 3043. We grouped serum MBL and MBL expression genotypes into three categories: low, intermediate, and high. Outcomes were CVE (myocardial infarction, stroke, coronary revascularization, unstable angina, and cardiovascular death) and all-cause mortality. The association with outcomes was examined by spline and Cox regression analyses. </p> <p><b>Results</b>: Serum MBL and CVE showed a U-shaped association. Compared to the intermediate serum MBL category, the adjusted hazard ratio (HR) for CVE was 1.82 (95% CI, 1.34 to 2.46) for the low-MBL category and 1.48 (95% CI, 1.14 to 1.92) for the high-MBL category. We found a similar U-shaped association for all-cause mortality, but with lower risk estimates. Compared to the intermediate MBL expression genotype, the adjusted HR for CVE was 1.40 (95% CI, 0.87 to 2.25) for the low-expression genotype and 1.44 (95% CI, 1.01 to 2.06) for the high-expression genotype. MBL expression genotype was not associated with all-cause mortality. </p> <p><b>Conclusions:</b> Both serum MBL and MBL expression genotype showed a U-shaped association with CVE risk in individuals with type 2 diabetes. Our findings suggest that serum MBL is a risk factor for cardiovascular disease in this population.</p>


2019 ◽  
Vol 21 (8) ◽  
pp. 1935-1943 ◽  
Author(s):  
Shahnam Sharif ◽  
Rolf H. H. Groenwold ◽  
Yolanda Graaf ◽  
Gijs F. N. Berkelmans ◽  
Maarten J. Cramer ◽  
...  

2020 ◽  
Vol 105 (7) ◽  
pp. 2371-2380 ◽  
Author(s):  
Mikael Croyal ◽  
Pierre-Jean Saulnier ◽  
Audrey Aguesse ◽  
Elise Gand ◽  
Stéphanie Ragot ◽  
...  

Abstract Objective Even though trimethylamine N-oxide (TMAO) has been demonstrated to interfere with atherosclerosis and diabetes pathophysiology, the association between TMAO and major adverse cardiovascular events (MACE) has not been specifically established in type 2 diabetes (T2D). Research Design and Methods We examined the association of plasma TMAO concentrations with MACE and all-cause mortality in a single-center prospective cohort of consecutively recruited patients with T2D. Results The study population consisted in 1463 SURDIENE participants (58% men), aged 65 ± 10 years. TMAO concentrations were significantly associated with diabetes duration, renal function, high-density lipoprotein cholesterol, soluble tumor necrosis factor receptor 1 (sTNFR1) concentrations (R2 = 0.27) and were significantly higher in patients on metformin, even after adjustment for estimated glomerular filtration rate (eGFR): 6.7 (8.5) vs 8.5 (13.6) µmol/L, respectively (PeGFR-adjusted = 0.0207). During follow-up (median duration [interquartile range], 85 [75] months), 403 MACE and 538 deaths were registered. MACE-free survival and all-cause mortality were significantly associated with the quartile distribution of TMAO concentrations, patients with the highest TMAO levels displaying the greatest risk of outcomes (P &lt; 0.0001). In multivariate Cox models, compared with patients from the first 3 quartiles, those from the fourth quartile of TMAO concentration had an independently increased risk for MACE: adjusted hazard ratio (adjHR) 1.32 (1.02-1.70); P = 0.0325. Similarly, TMAO was significantly associated with mortality in multivariate analysis: adjHR 1.75 (1.17-2.09); P = 0.0124, but not when sTNFR1 and angiopoietin like 2 were considered: adjHR 1.16 (0.95-1.42); P = 0.1514. Conclusions We revealed an association between higher TMAO concentrations and increased risk of MACE and all-cause mortality, thereby opening some avenues on the role of dysbiosis in cardiovascular risk, in T2D patients.


Diabetologia ◽  
2021 ◽  
Author(s):  
Simon R. Heller ◽  
Milan S. Geybels ◽  
Ahmed Iqbal ◽  
Lei Liu ◽  
Lily Wagner ◽  
...  

Abstract Aims/hypothesis Hypoglycaemia is a common side effect of insulin and some other antihyperglycaemic agents used to treat diabetes. Severe hypoglycaemia has been associated with adverse cardiovascular events in trials of intensive glycaemic control in type 2 diabetes. The relationship between non-severe hypoglycaemic episodes (NSHEs) and severe hypoglycaemia in type 2 diabetes has been documented. However, an association between more frequent NSHEs and cardiovascular events has not been verified. This post hoc analysis of the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results) trial aimed to confirm whether there is an association between NSHEs and severe hypoglycaemic episodes in individuals with type 2 diabetes. In addition, the possible association between NSHEs and major adverse cardiac events (MACE), cardiovascular death and all-cause mortality was investigated. Methods LEADER was a double-blind, multicentre, placebo-controlled trial that found that liraglutide significantly reduced the risk of MACE compared with the placebo. In this post hoc analysis, we explored, in all LEADER participants, whether the annual rate of NSHEs (defined as self-measured plasma glucose <3.1 mmol/l [56 mg/dl]) was associated with time to first severe hypoglycaemic episode (defined as an episode requiring the assistance of another person), time to first MACE, time to cardiovascular death and time to all-cause mortality. Participants with <2 NSHEs per year were used as reference for HR estimates. Cox regression with a time-varying covariate was used. Results We demonstrate that there is an association between NSHEs (2–11 NSHEs per year and ≥12 NSHEs per year) and severe hypoglycaemic episodes (unadjusted HRs 1.98 [95% CI 1.43, 2.75] and 5.01 [95% CI 2.84, 8.84], respectively), which was consistent when baseline characteristics were accounted for. Additionally, while no association was found between participants with 2–11 NSHEs per year and adverse cardiovascular outcomes, higher rates of NSHEs (≥12 episodes per year) were associated with higher risk of MACE (HR 1.50 [95% CI 1.01, 2.23]), cardiovascular death (HR 2.08 [95% CI 1.17, 3.70]) and overall death (HR 1.80 [95% CI 1.11, 2.92]). Conclusions/interpretation The analysis of data from the LEADER trial demonstrated that higher rates of NSHEs were associated with both a higher risk of severe hypoglycaemia and adverse cardiovascular outcomes in individuals with type 2 diabetes. Therefore, irrespective of the cause of this association, it is important that individuals with high rates of hypoglycaemia are identified so that the potentially increased risk of cardiovascular events can be managed and steps can be taken to reduce NSHEs. Trial registration ClinicalTrials.gov (NCT01179048). Graphical abstract


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