scholarly journals Risk of Major Adverse Cardiovascular Events, Severe Hypoglycemia, and All-Cause Mortality for Widely Used Antihyperglycemic Dual and Triple Therapies for Type 2 Diabetes Management: A Cohort Study of All Danish Users

Diabetes Care ◽  
2020 ◽  
Vol 43 (6) ◽  
pp. 1209-1218
Author(s):  
Morten Hasselstrøm Jensen ◽  
Mads Kjolby ◽  
Ole Hejlesen ◽  
Poul Erik Jakobsen ◽  
Peter Vestergaard
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>


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.


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