Abstract P274: Kidney Filtration Markers and the Risk of Clinical Outcomes in Individuals With Type 2 Diabetes in the Advance Trial

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Hyunju Kim ◽  
Dan Wang ◽  
John Chalmers ◽  
Mark Woodward ◽  
Elizabeth Selvin ◽  
...  

Introduction: Creatinine-based estimated glomerular filtration rate (eGFR) is biased in the setting of obesity and other conditions. Alternative kidney filtration markers may be particularly useful in adults with diabetes, but few studies examined the risk of clinical outcomes associated with filtration markers in adults with type 2 diabetes. Objective: We evaluated whether baseline levels and change in eGFR based on creatinine (Cr), cystatin C (Cys), and B 2 -microglobulin (B2M) were associated with the risk of clinical outcomes among individuals with type 2 diabetes. Methods: In the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, Cr, Cys, and B2M were measured in 7,217 participants at baseline and a random sample of 640 participants at the 1 year visit. We categorized baseline eGFR Cr , eGFR Cys , eGFR B2M , and the average across the 3 eGFR estimates (eGFR avg ) into quarters, and examined associations with major macrovascular and microvascular events together, and separately, and all-cause mortality using Cox regression models, adjusting for established risk factors. We also examined associations with continuous eGFR decline and increase (per 30%). Results: Over a median follow-up of 5 years, 1,313 combined major macrovascular (n=748) and microvascular events (n=637), and 743 deaths occurred. Lower levels of eGFR based on all three filtration markers individually and combined were associated with 1.5 to 2.2 times higher risk of combined major macrovascular and microvascular events, with similar patterns for other outcomes ( Table ). Per 30% decline in eGFR Cys and eGFR avg were associated with a >2-fold higher risk of all clinical outcomes, after additional adjustment of baseline eGFR. Conclusions: In adults with type 2 diabetes, baseline levels of eGFR based on alternative filtration markers and per 30% decline in eGFR Cys and eGFR avg were consistently associated with all clinical outcomes.

2016 ◽  
Vol 209 (2) ◽  
pp. 142-149 ◽  
Author(s):  
Giesje Nefs ◽  
Victor J. M. Pop ◽  
Johan Denollet ◽  
François Pouwer

BackgroundDepression has been associated with increased all-cause mortality in people with type 2 diabetes.AimsTo test whether anhedonia, dysphoria and anxiety are differentially associated with all-cause mortality and examine symptom-specific behavioural or pathophysiological mechanisms.MethodA total of 1465 people completed the Edinburgh Postnatal Depression Scale in 2005 and were followed until death or 31 December 2010. Cox regression analyses compared survival time for people with a low v. high baseline dysphoria/anhedonia/anxiety score and identified mediating mechanisms.ResultsAfter a mean follow-up of 1878 days (s.d. = 306), 139 participants had died. At all time points, people with anhedonia had an almost twofold increased mortality risk compared with those without anhedonia. Physical activity met criteria for mediation. Symptoms of dysphoria and anxiety were not associated with survival time.ConclusionsSymptoms of anhedonia predicted shorter survival time, whereas dysphoria/anxiety did not. Mechanistic pathways, in particular physical activity, should be explored further.


2021 ◽  
Author(s):  
Maoxiang Zhao ◽  
Lulu Song ◽  
Lan Sun ◽  
Miao Wang ◽  
Chi Wang ◽  
...  

<b>Objective</b><b></b> <p>We aimed to explore the associations between type 2 diabetes onset age and cardiovascular disease (CVD) and all-cause mortality in Chinese population.</p> <p><b>Research design and methods</b></p> <p>This study included 101,080 participants free of prevalent diabetes and CVD at baseline from the Kailuan study. All participants were followed biennially until December 31, 2017. A total of 11,384 participants were diagnosed as type 2 diabetes during follow-up. For each case, one control was randomly selected matched for age (±1 years) and sex. The final analysis comprised 10,777 case-control pairs. Weighted Cox regression models were used to evaluate the average hazard ratios (AHRs) and 95% confidence intervals (CIs) of incident CVD and all-cause mortality among patients with new-onset type 2 diabetes <i>versus </i>controls across age groups.</p> <p><b>Results</b><b></b></p> <p>During a median follow-up of 5.57 years, 1794 incident events (907 CVD events, of which were 725 strokes, and 887 deaths) occurred. After adjustment for potential confounders, participants with type 2 diabetes diagnosed at age < 45 years had the highest risks of CVD and all-cause mortality relative to the matched controls, with AHRs of 3.21 (95% CI 1.18–8.72) for CVD, 2.99 (95% CI 1.01–9.17) for stroke, and 4.79 (95% CI 1.95–11.76) for all-cause mortality. The risks gradually attenuated with each decade increase in type 2 diabetes onset age. </p> <p><b>Conclusions</b><b></b></p> <p>The relative risks of CVD and all-cause mortality differed across type 2 diabetes onset age groups, and the associations were more evident in younger-onset type 2 diabetes. </p>


Obesity Facts ◽  
2021 ◽  
pp. 1-10
Author(s):  
Britt W. Jensen ◽  
Charlotte Watson ◽  
Nophar Geifman ◽  
Jennifer L. Baker ◽  
Ellena Badrick ◽  
...  

<b><i>Introduction:</i></b> Body mass index (BMI) is often elevated at type 2 diabetes (T2D) diagnosis. Using latent class trajectory modelling (LCTM) of BMI, we examined whether weight loss after diagnosis influenced cancer incidence and all-cause mortality. <b><i>Methods:</i></b> From 1995 to 2010, we identified 7,708 patients with T2D from the Salford Integrated Record database (UK) and linked to the cancer registry for information on obesity-related cancer (ORC), non-ORC; and all-cause mortality. Repeated BMIs were used to construct sex-specific latent class trajectories. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression models. <b><i>Results:</i></b> Four sex-specific BMI classes were identified; stable-overweight, stable-obese, obese-slightly-decreasing, and obese-steeply-decreasing; comprising 41%, 45%, 13%, and 1% of women, and 45%, 37%, 17%, and 1% of men, respectively. In women, the stable-obese class had similar ORC risks as the obese-slightly-decreasing class, whereas the stable-overweight class had lower risks. In men, the obese-slightly-decreasing class had higher risks of ORC (HR = 1.86, 95% CI: 1.05–3.32) than the stable-obese class, while the stable-overweight class had similar risks No associations were observed for non-ORC. Compared to the stable-obese class, women (HR = 1.60, 95% CI: 0.99–2.58) and men (HR = 2.37, 95% CI: 1.66–3.39) in the obese-slightly-decreasing class had elevated mortality. No associations were observed for the stable-overweight classes. <b><i>Conclusion:</i></b> Patients who lost weight after T2D diagnosis had higher risks for ORC (in men) and higher all-cause mortality (both genders) than patients with stable obesity.


2021 ◽  
Author(s):  
Maoxiang Zhao ◽  
Lulu Song ◽  
Lan Sun ◽  
Miao Wang ◽  
Chi Wang ◽  
...  

<b>Objective</b><b></b> <p>We aimed to explore the associations between type 2 diabetes onset age and cardiovascular disease (CVD) and all-cause mortality in Chinese population.</p> <p><b>Research design and methods</b></p> <p>This study included 101,080 participants free of prevalent diabetes and CVD at baseline from the Kailuan study. All participants were followed biennially until December 31, 2017. A total of 11,384 participants were diagnosed as type 2 diabetes during follow-up. For each case, one control was randomly selected matched for age (±1 years) and sex. The final analysis comprised 10,777 case-control pairs. Weighted Cox regression models were used to evaluate the average hazard ratios (AHRs) and 95% confidence intervals (CIs) of incident CVD and all-cause mortality among patients with new-onset type 2 diabetes <i>versus </i>controls across age groups.</p> <p><b>Results</b><b></b></p> <p>During a median follow-up of 5.57 years, 1794 incident events (907 CVD events, of which were 725 strokes, and 887 deaths) occurred. After adjustment for potential confounders, participants with type 2 diabetes diagnosed at age < 45 years had the highest risks of CVD and all-cause mortality relative to the matched controls, with AHRs of 3.21 (95% CI 1.18–8.72) for CVD, 2.99 (95% CI 1.01–9.17) for stroke, and 4.79 (95% CI 1.95–11.76) for all-cause mortality. The risks gradually attenuated with each decade increase in type 2 diabetes onset age. </p> <p><b>Conclusions</b><b></b></p> <p>The relative risks of CVD and all-cause mortality differed across type 2 diabetes onset age groups, and the associations were more evident in younger-onset type 2 diabetes. </p>


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 453-P
Author(s):  
MONIA GAROFOLO ◽  
ELISA GUALDANI ◽  
DANIELA LUCCHESI ◽  
LAURA GIUSTI ◽  
VERONICA SANCHO-BORNEZ ◽  
...  

2020 ◽  
Author(s):  
Feifei Cheng ◽  
Andrea O Luk ◽  
Claudia HT Tam ◽  
Baoqi Fan ◽  
Hongjiang Wu ◽  
...  

<b>Objective</b>: Several studies support potential links between leukocyte relative telomere length (rLTL), a biomarker of biological aging and type 2 diabetes. This study investigates relationships between rLTL and subsequent cardiovascular disease (CVD) in patients with type 2 diabetes. <p><b>Research design and methods</b>: Consecutive Chinese patients with type 2 diabetes (N=5349) from the Hong Kong Diabetes Register with stored baseline DNA and available follow-up data were studied. rLTL was measured using quantitative polymerase chain reaction. CVD was diagnosed based on ICD-9 code.</p> <p><b>Results: </b>Mean (SD) follow-up was 13.4(5.5) years. rLTL was correlated inversely with age, diabetes duration, blood pressure, HbA<sub>1c</sub>, urine ACR and positively with eGFR (all P<0.001). Subjects with versus without CVD at baseline had shorter rLTL (4.3±1.2 vs. 4.6±1.2, P<0.001). Of the 4541 CVD-free subjects at baseline, the 1140 who developed CVD during follow-up had shorter rLTL than those remaining CVD-free after adjusting for age, sex, smoking and albuminuria status (4.3±1.2 vs. 4.7±1.2, P<0.001). In Cox regression models, shorter rLTL was associated with higher risk of incident CVD (hazard ratio (95% CI) for each unit decrease: 1.252 (1.195-1.311), P<0.001), which remained significant after adjusting for age, sex, BMI, SBP, LDL-C, HbA<sub>1c</sub>, eGFR and ACR (hazard ratio (95% CI): 1.141 (1.084-1.200), P<0.001).</p> <p><b>Conclusions: </b>rLTL is significantly shorter in type 2 diabetes patients with CVD, is associated with cardiometabolic risk factors, and is independently associated with incident CVD. Telomere length may be a useful biomarker for CVD risk in type 2 diabetes.</p> <b><br> </b>


2020 ◽  
Author(s):  
Katsuhito Ihara ◽  
Jan Skupien ◽  
Hiroki Kobayashi ◽  
Zaipul I. Md Dom ◽  
Jonathan M. Wilson ◽  
...  

<b>OBJECTIVE</b>: The role of fibrosis in early progressive renal decline in type 2 diabetes is unknown. Circulating WFDC2 (WAP four-disulfide core domain protein 2) and MMP-7 (Matrilysin) are postulated to be biomarkers of renal fibrosis. This study examined an association of circulating levels of these proteins with early progressive renal decline. <p><b>RESEARCH DESIGN AND METHODS</b>: Individuals with type 2 diabetes enrolled in the Joslin Kidney Study with eGFR ≥60 ml/min/1.73m<sup>2</sup> were followed for 6-12 years to ascertain fast early progressive renal decline defined as eGFR loss ≥5 ml/min/1.73m<sup>2</sup>/year. </p> <p><b>RESULTS</b>: A total of 1,181 individuals were studied: 681 without and 500 with albuminuria. Median eGFR and ACR at baseline were 97 ml/min/1.73m<sup>2</sup> and 24 mg/g, respectively. During follow-up, 152 individuals experienced fast early progressive renal decline: 6.9% in those with normoalbuminuria and 21% with albuminuria. In both subgroups risk of renal decline increased with increasing baseline levels of WFDC2 (p <0.0001) and MMP-7 (p <0.0001). After adjustment for relevant clinical characteristics and known biomarkers, an increase by one quartile in the Fibrosis Index (combination of levels of WFDC2 and MMP-7) was associated with higher risk of renal decline (OR 1.63; 95% CI 1.30-2.04). The association was similar and statistically significant among patients with and without albuminuria. </p> <p><b>CONCLUSIONS: </b>Elevation of circulating profibrotic proteins is associated with the development of early progressive renal decline in type 2 diabetes. This association is independent from albuminuria status and points to the importance of the fibrotic process in development of early renal decline. </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 ◽  
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>


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