Variability in body weight and the risk of cardiovascular complications in type 2 diabetes: results from the Swedish National Diabetes Register

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Antonio Ceriello ◽  
Giuseppe Lucisano ◽  
Francesco Prattichizzo ◽  
Björn Eliasson ◽  
Stefan Franzén ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Body Weight ◽  
Cardiovascular Complications ◽  
Composite Outcome ◽  
All Cause Mortality ◽  
Diabetes Register ◽  
Primary Composite Outcome ◽  
Fatal Myocardial Infarction

Abstract Background There is a high incidence of cardiovascular disease in diabetes. Weight variability has been reported as independent risk factor for cardiovascular disease in the general population and preliminarily also in people with type 2 diabetes. Methods Using data from the Swedish National Diabetes Register the possible link between visit-to-visit body weight variability and the risk of cardiovascular complications among people with type 2 diabetes and without prevalent cardiovascular diseases at baseline has been evaluated. Overall, 100,576 people with type 2 diabetes, with at least five measurements of body weight taken over three consecutive years, were included. Variability was expressed as quartiles of the standard deviation of the measures during the three years. The primary composite outcome included non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality and was assessed during five years following the first 3 years of exposure to weight variability. Results After adjusting for known cardiovascular risk factors, the risk of the primary composite outcome significantly increased with increasing body weight variability [upper quartile HR = 1.45; 95% confidence interval 1.39–1.52]. Furthermore, elevated body weight variability was associated with almost all the other cardiovascular complications considered (non-fatal myocardial infarction, non-fatal stroke, all-cause mortality, peripheral arterial disease, peripheral vascular angioplasty, hospitalization for heart failure, foot ulcer, and all-cause mortality). Conclusions High body weight variability predicts the development of cardiovascular complications in type 2 diabetes. These data suggest that any strategy to reduce the body weight in these subjects should be aimed at maintaining the reduction in the long-term, avoiding oscillations.

Abstract 123: Replicating the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Trial in Real-World Claims Data

2012 ◽  
Vol 5 (suppl_1) ◽  
Author(s):  
Bijan J Borah ◽  
Nilah D Shah ◽  
Victor M Montori
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Risk ◽  
Risk Reduction ◽  
Composite Outcome ◽  
Cardiovascular Risk Reduction ◽  
All Cause Mortality ◽  
Secondary Outcomes ◽  
Primary Composite Outcome

Background: The ACCORD-Lipid Trial’s finding that statin-fibrate combination therapy (CT) provides no incremental cardiovascular risk reduction in type 2 diabetese over statin monotherapy (MT) prompted FDA to issue a public communication on 11/9/2011 stating that fenofibrate may not reduce risk of heart attack or stroke. Yet, fibrate use continues unabated with over $1 billion in sales in the US that raises concern regarding the inconsistency in diffusion of scientific evidence into clinical practice. Critics of ACCORD findings maintain that ACCORD trial adopted flexible thresholds for qualifying HDL and triglyceride levels and that it left unanswered whether the effects of non-ACCORD statins or fibrates or combinations thereof will be different. By replicating the ACCORD-Lipid trial as closely as possible using 16-year longitudinal claims database from a large national health plan, our study seeks to compare the following ACCORD outcomes between CT and MT cohorts: (i) primary composite outcome of nonfatal MI, nonfatal stroke and cardiovascular death; (ii) secondary outcomes of all-cause mortality, expanded macrovascular outcome, major CAD events and CHF. Methods (Research Design, Data Source and Data Analysis Methods) : Retrospective claims analysis that included patients enrolled between 1995 and 2010 using ACCORD inclusion/exclusion criteria including type 2 diabetes patients aged 40 to 79 with baseline A1C≥7.5 and on statin. Patients in the two study cohorts, CT and MT, were required to have minimum of 1-year baseline and 90-day follow-up periods. Propensity score (PS) matching was used to adjust for patient baseline characteristics. T- and Chi-squared tests were used to assess differences in continuous and categorical covariates and Cox proportional hazard model was used to assess the hazard of study events. Results: The study included 6765 patients (CT=954; MT=5811) with a mean follow-up of 2.4 years. An average patient in the sample was a White male aged 57 years from the South. The two study cohorts differed in demographics (age, female, ethnicity, income categories), baseline lipids (HDL, LDL, triglyceride and HbA1c), and in numerous comorbid conditions. After 1-to-1 PS matching, baseline LDL, triglycerides and total cholesterol were similar but HDL (HbA1c) was higher (lower) in CT than in MT cohort (n=943 in each cohort). Most other baseline covariates were balanced. Unadjusted results showed that compared to MT, CT cohort had higher primary composite outcomes (62 vs 45), all-cause deaths (113 vs 105), macrovascular events (16 vs 9), major CAD (84 vs 59), nonfatal stroke (35 vs 33) and CHF (60 vs 51). Adjusted results show no difference in the rate of primary composite outcome (hazard rate or HR=1.44, p=0.09) and in secondary outcomes of macrovascular events (HR=1.61), all-cause mortality (HR=1.22), major CAD (HR=1.45), CHF (HR=1.24) and non-fatal stroke (HR=0.98) [all p>.05] Conclusion: The study results appear to confirm the non-significance of CT over MT in cardiovascular risk reduction among type 2 diabetes patients in a large US commercial health plan.

scholarly journals Body Weight Variability and the Risk of Cardiovascular Outcomes and Mortality in Patients with Type 2 Diabetes: a Nationwide Cohort Study

2020 ◽  
Author(s):  
Ga Eun Nam ◽  
Wonsock Kim ◽  
Kyungdo Han ◽  
Chung-woo Lee ◽  
Yeongkeun Kwon ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Body Weight ◽  
Large Scale ◽  
Cox Proportional Hazards ◽  
Cardiovascular Outcomes ◽  
National Health Insurance System ◽  
All Cause Mortality ◽  
Quartile Group ◽  
Diabetes Patients

<b>Objective: </b>Obesity and type 2 diabetes are risk factors for cardiovascular diseases and mortality, and that commonly result in weight variabilities. We aimed to investigate the association between body weight variability and risk of major cardiovascular outcomes and mortality in individuals with type 2 diabetes using large-scale, nationwide cohort data on the Korean population. <div><p><b>Research Design and Methods: </b>We enrolled 624,237 individuals with type 2 diabetes who underwent health examinations provided by the Korean National Health Insurance System between 2009 and 2010, with ≥3 body weight measurements within 5 years since enrollment and followed up until the end of 2017. We assessed body weight variability using four indices, including variability independent of the mean (VIM). Multivariable-adjusted Cox proportional hazards regression analysis was performed.</p> <p><b>Results: </b>During the follow-up, 15,832, 25,038, and 44,716 cases of myocardial infarction (MI), stroke, and all-cause mortality, respectively, were recorded. Body weight variability was associated with increased risks of major cardiovascular outcomes after adjusting for confounding variables. Compared with the hazard ratios (HRs) of the lowest quartile group, the HRs (95% CIs) of the highest quartile group of VIM for body weight were 1.15 (1.10–1.20), 1.22 (1.18–1.26), and 1.58 (1.53–1.62) for MI, stroke, and all-cause mortality, respectively.</p> <p><b>Conclusions: </b>Body weight variability was associated with increased risks of MI, stroke, and all-cause mortality in type 2 diabetes patients and may be a predictor of cardiovascular outcomes in such patients. Appropriate interventions to maintain stable weight could positively influence health outcomes in type 2 diabetes patients.</p> </div> <br>

408Albuminuria as a predictor of incident ischemic stroke and myocardial infarction in patients with type 2 diabetes but without cardiovascular disease: A Danish cohort study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
M V Fangel ◽  
P B Nielsen ◽  
J K Kristensen ◽  
T B Larsen ◽  
T F Overvad ◽  
...  
Keyword(s):  
Risk Factors ◽  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cohort Study ◽  
Ischemic Stroke ◽  
Cardiovascular Risk ◽  
All Cause Mortality ◽  
Patients With Diabetes

Abstract Background Risk stratification in patients with type 2 diabetes continues to be an important priority in the management of diabetes-related morbidity and mortality. International guidelines generally recognize patients with diabetes and cardiovascular disease as high-risk patients. Risk stratification is, however, more uncertain in diabetes patients without cardiovascular disease. Micro- and macroalbuminuria have previously been identified as predictors of cardiovascular events and mortality in general cohorts of diabetes patients. However, less is known about the predictive value of albuminuria in patients with diabetes but without established cardiovascular disease. Purpose We aimed to examine the association between albuminuria level and the risk of ischemic stroke, myocardial infarction, and all-cause mortality in patients with type 2 diabetes and without a diagnosis of cardiovascular disease. Methods We linked Danish nationwide registries to identify patients with type 2 diabetes and without cardiovascular disease from May 2005 through June 2015. Based on two consecutive measurements of the urinary albumin excretion rate or albumin-to-creatinine ratio patients were stratified in categories of normoalbuminuria, microalbuminuria, and macroalbuminuria. Patients were followed for the outcomes ischemic stroke, myocardial infarction, and all-cause mortality until December 31, 2015. Five-year risk of outcomes were presented as cumulative incidence functions (with death as a competing event). Associations between albuminuria level and incidence of ischemic stroke, myocardial infarction, and all-cause mortality were evaluated with Cox proportional hazard regression adjusted for cardiovascular risk factors. Results The study population included 78,841 patients with type 2 diabetes (44.7% females, mean age 63.2). When comparing patients with microalbuminuria to patients with normoalbuminuria in an age- and sex-adjusted analysis, we found hazard ratios (HRs) of 1.45 (95% CI: 1.24–1.69), 1.45 (95% CI: 1.24–1.70), and 1.50 (95% CI: 1.39–1.61) for ischemic stroke, myocardial infarction, and all-cause mortality, respectively. Furthermore, macroalbuminuria was associated with HRs of 2.05 (95% CI: 1.70–2.48), 2.25 (95% CI: 1.86–2.71), and 2.03 (95% CI: 1.85–2.23) for ischemic stroke, myocardial infarction, and all-cause mortality, respectively. Similar results were found after adjusting for cardiovascular risk factors. Conclusions In this nationwide cohort study of patients with type 2 diabetes but without cardiovascular disease, patients with micro- and macroalbuminuria had a higher risk of incident ischemic stroke, myocardial infarction, and all-cause mortality. This finding supports that patients with micro- or macroalbuminuria should be screened regularly and followed closely in clinical practice. Moreover, these findings suggest that patients with type 2 diabetes and micro- or macroalbuminuria may benefit from intensive vascular risk reduction.

scholarly journals Mediators of the effect of ertugliflozin on a composite kidney outcome in patients with type 2 diabetes and atherosclerotic cardiovascular disease: analyses from VERTIS CV

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
D Z I Cherney ◽  
M Segar ◽  
A Pandey ◽  
C P Cannon ◽  
F Cosentino ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Body Weight ◽  
Uric Acid ◽  
Serum Uric Acid ◽  
Atherosclerotic Cardiovascular Disease ◽  
Composite Outcome ◽  
Average Change ◽  
Post Randomisation

Abstract Introduction Sodium–glucose cotransporter 2 (SGLT2) inhibitors have been shown to slow the decline of kidney function in outcome trials, but the biological mediator(s) underlying the therapeutic benefit are not well established. Purpose We performed a post-hoc analysis exploring potential mediators of the effects of the SGLT2 inhibitor ertugliflozin on the VERTIS CV exploratory kidney composite outcome (sustained 40% decrease from baseline in estimated glomerular filtration rate [eGFR], chronic kidney replacement therapy or kidney death). Methods In VERTIS CV, 8246 participants with type 2 diabetes mellitus and established atherosclerotic cardiovascular disease were randomised to placebo, ertugliflozin 5 mg or 15 mg (pooled for analyses, as prospectively planned), and were followed for a mean of 3.5 years. The hazard ratio (HR; 95% confidence interval) for the pre-specified exploratory kidney composite outcome was 0.66 (0.50, 0.88). Cox regression models were used to evaluate covariates that were significantly differentially changed from baseline with ertugliflozin treatment as candidate mediators, with a mediator identified as a covariate when added to an unadjusted model of randomised treatment assignment a) yielded a larger hazard ratio; and b) the mediator retained P&lt;0.05 in the model (eGFR was excluded as a covariate). The percentage of mediation was determined by the proportional increase in the HR between the unadjusted and adjusted models for each post-randomisation period: early (first change from baseline measurement) and average (weighted average of change from baseline from all post-baseline measurements). Each potential mediator was tested individually, so across analyses, mediation % sums to &gt;100%. Results Of 22 covariates significantly changed by ertugliflozin, nine were identified as potential mediators (Table). The covariates with a high percentage of mediation were those related to changes in blood erythrocytes (haemoglobin, haematocrit and red blood cell mass), with average changes in haemoglobin having the highest percentage of mediation (61.8%). Serum uric acid was associated with a mediation of 29.4% and 50.0% for the early and average post-randomisation effect periods, respectively. Early changes in glycated haemoglobin had a large mediation (50%), but the average change during the trial was not significant. Average change in serum albumin had a large mediation (29.4%). Average changes in body weight and systolic blood pressure had percentages of mediation of 41.2% and 14.7%, respectively. Conclusion Multiple factors may be involved in the reduction of the kidney composite outcome observed with ertugliflozin. In the short-term, changes in glycaemia had a high mediation effect. Over the long-term, changes suggestive of haemoconcentration and/or haematopoiesis (natriuresis-related effects), showed the highest percentage of mediation, followed by changes in serum uric acid and body weight (glucosuria-related effects). FUNDunding Acknowledgement Type of funding sources: Private company. Main funding source(s): Sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA in collaboration with Pfizer Inc., New York, NY, USA

scholarly journals Pleiotropic Effects of Pure Statin May Provide More Cardiac Benefits than Ezetimibe-Statin in a Comparable Intensity for Type 2 Diabetes Mellitus Patients with Extremely Atherosclerotic Cardiovascular Disease Risks

2020 ◽  
Author(s):  
Yu-Cheng Kao ◽  
Tien-Hsing Chen ◽  
Chi-Hung Liu ◽  
Jawl-Shan Hwang ◽  
Ching-Chung Hsiao ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Pleiotropic Effects ◽  
Research Database ◽  
Composite Outcome ◽  
Coronary Syndrome ◽  
Significant Difference ◽  
Primary Composite Outcome

Abstract Background: Atorvastatin 40mg (ATOR 40) and ezetimibe 10mg/simvastatin 20mg (EZ-SIM 20) have comparable reductions of low-density lipoprotein cholesterol (LDL-C) but cardiovascular (CV) outcomes between these two therapies are unclear. Our real-world cohort study is to test the hypothesis of pleiotropic effects of purely higher dose statin on CV outcomes beyond comparable reductions of LDL-C, especially for extremely CV risk patients.Methods: Between January 1, 2007 and December 31, 2013, a total of 3372 patients with type 2 diabetes mellitus (T2DM) admitted due to acute coronary syndrome (ACS) or acute ischemic stroke (AIS) were selected as the study cohort from the Taiwan National Health Insurance Research Database. Clinical outcomes were evaluated by ATOR 40 group (n=1686) matched with EZ-SIM 20 group (n=1686). Primary composite outcome includes CV death, non-fatal myocardial infarction, and non-fatal stroke. Secondary composite outcome includes hospitalization for unstable angina (HUA), percutaneous coronary intervention (PCI), and coronary artery bypass grafting (CABG).Results: With a mean follow-up of 2.4 years, no significant difference of primary composite outcome was observed between ATOR 40 and EZ-SIM 20 groups (subdistribution hazard ratio [SHR], 1.09; 95% confidence interval [CI], 0.95–1.25). Nevertheless, ATOR 40 group had lower risks of HUA (SHR, 0.50; 95% CI, 0.35–0.72), PCI (SHR, 0.82; 95% CI, 0.69–0.97) and CABG (SHR, 0.62; 95% CI, 0.40–0.97) than EZ-SIM 20 group.Conclusions: For T2DM patients after ACS or AIS, ATOR 40 may have lower risks of HUA, PCI and CABG than EZ-SIM 20.

scholarly journals Low-grade inflammation as a risk factor for cardiovascular events and all-cause mortality in patients with type 2 diabetes

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Shahnam Sharif ◽  
Y. Van der Graaf ◽  
M. J. Cramer ◽  
L. J. Kapelle ◽  
G. J. de Borst ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Cardiovascular Events ◽  
Low Grade ◽  
All Cause Mortality ◽  
High Risk Type ◽  
Hs Crp ◽  
Low Grade Inflammation ◽  
Diabetes Patients

Abstract Background Type 2 diabetes is a condition associated with a state of low-grade inflammation caused by adipose tissue dysfunction and insulin resistance. High sensitive-CRP (hs-CRP) is a marker for systemic low-grade inflammation and higher plasma levels have been associated with cardiovascular events in various populations. The aim of the current study is to evaluate the relation between hs-CRP and incident cardiovascular events and all-cause mortality in high-risk type 2 diabetes patients. Methods Prospective cohort study of 1679 type 2 diabetes patients included in the Second Manifestations of ARTerial disease (SMART). Cox proportional hazard models were used to evaluate the risk of hs-CRP on cardiovascular events (composite of myocardial infarction, stroke and vascular mortality) and all-cause mortality. Hs-CRP was log-transformed for continuous analyses. Findings were adjusted for age, sex, BMI, current smoking and alcohol use, non-HDL-cholesterol and micro-albuminuria. Results 307 new cardiovascular events and 343 deaths occurred during a median follow-up of 7.8 years (IQR 4.2–11.1). A one unit increase in log(hs-CRP) was related to an increased vascular- and all-cause mortality risk (HR 1.21, 95% CI 1.01–1.46 and HR 1.26, 95% CI 1.10–1.45 respectively). No relation was found between log(hs-CRP) and myocardial infarction or stroke. The relations were similar in patients with and without previous vascular disease. Conclusion Low grade inflammation, as measured by hs-CRP, is an independent risk factor for vascular- and all-cause mortality but not for cardiovascular events in high-risk type 2 diabetes patients. Chronic low-grade inflammation may be a treatment target to lower residual cardiovascular risk in type 2 diabetes patients.

Abstract 2365: Pharmacogenomic Application Of The Haptoglobin Genotype To Identify Individuals With Diabetes Mellitus Who Benefit From Vitamin E Supplementation: A Prospective Randomized, Double-blind, Placebo Controlled Trial

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Uzi Milman ◽  
Shany Blum ◽  
Chen Shapira ◽  
Doron Aronson ◽  
Rachel Miller-Lotan ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Vitamin E ◽  
Cardiovascular Events ◽  
Cardiovascular Death ◽  
Composite Outcome ◽  
Anti Oxidant ◽  
Primary Composite Outcome ◽  
Fatal Myocardial Infarction ◽  
Vitamin E Supplementation

Background. Large clinical trials of antioxidant therapy with vitamin E have failed to demonstrate a decrease in cardiovascular events. However, these studies did not address possible benefit to subgroups with increased oxidative stress. Haptoglobin (Hp), a major anti-oxidant protein, is a determinant of cardiovascular events in patients with diabetes mellitus (DM). The Hp gene is polymorphic with two common alleles, 1 and 2. The Hp 2 allelic protein product provides inferior anti-oxidant protection as compared to the Hp 1 allelic product. In a retrospective analysis of HOPE participants with DM and the Hp 2–2 genotype, vitamin E significantly reduced the incidence of myocardial infarction and cardiovascular death. We sought to validate this observation in a prospective trial. Methods and Results. 984 DM individuals with the Hp 2–2 genotype were randomized and treated with either natural source vitamin E (400IU/day) or placebo. The primary composite outcome was non-fatal myocardial infarction, stroke and cardiovascular death. The study was intended to last 4 years with initial evaluation of endpoints scheduled 12 months after enrollment of the first patient. At the initial evaluation, the primary composite outcome was significantly reduced in patients receiving vitamin E compared to placebo (1.0% vs. 3.8%, p=0.004). This was predominately due to a significant decrease in the incidence of non-fatal myocardial infarction (0.2% vs. 2.1%, p=0.004) and led to early termination of the study. Conclusions . Vitamin E supplementation appears to reduce cardiovascular events in individuals with DM and the Hp 2–2 genotype. (ClinicalTrials.gov number NCT00220831 ).

Abstract 13625: Effect of Empagliflozin versus Placebo on Plasma Volume Status in Patients With Acute Myocardial Infarction and Type 2 Diabetes Mellitus: Subgroup Analysis of the Embody Trial

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Yu Hoshika ◽  
Yoshiaki Kubota ◽  
Kosuke Mozawa ◽  
Shuhei Tara ◽  
Yukichi Tokita ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Myocardial Infarction ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Body Weight ◽  
Placebo Group ◽  
Plasma Volume ◽  
Subgroup Analysis ◽  
Sglt2 Inhibitor

Background: Plasma volume status (PVS), a parameter of the discrepancy between actual plasma volume (PV) and ideal PV, has been evaluated recently as a prognostic marker of patients with heart failure. This subgroup analysis of the EMBODY trial was designed to determine whether the sodium-glucose cotransporter 2 (SGLT2) inhibitor affect the improvement of heart failure and PVS in patients after acute myocardial infarction (AMI) with congestive heart failure (CHF). Methods: The EMBODY trial was a prospective, multicenter, randomized, double-blind, placebo-controlled trial to identify the effect of the SGLT2 inhibitor on cardiac sympathetic hyperactivity in patients with AMI and type 2 diabetes mellitus (T2DM) in Japan. A total of one hundred and five patients were randomized (1:1) to receive once-daily 10 mg empagliflozin or placebo 2 weeks after the onset of AMI. In this subanalysis, we investigated the time-course of PVS on baseline, weeks 4, 12 and 24. Results: Overall, 96 patients were included in the subgroup analysis set (64.3±10.9 years, male 80.2%, and 46 in the empagliflozin group and 50 in the placebo group). The empagliflozin group showed significant decreases in body weight, systolic blood pressure, and PVS compared with the placebo group at 24 weeks (-2.2 vs. +0.1 kg, P=0.0007; -6.6 vs. +3.5 mmHg, P=0.003; and -5.1 vs. -0.3%, P=0.0006; respectively). Decreased of PVS, defined as change of PVS < -4.5 % was associated with received empagliflozin (odds ratio, 2.61; 95% confidence interval, 1.11 - 6.15; P=0.028). On the other hand, NT-Pro BNP levels significantly decreased in the empagliflozin group and placebo group (1028.7 to 370.3 pg/ml, P=0.0001 and 1270.6 to 673.7 pg/ml, P=0.006, respectively). Conclusion: Empagliflozin reduced not only body weight but also PVS. These results suggested that early SGLT2 inhibitor administration in patients with AMI, CHF and T2DM could be effective to reduce body weight and PVS.

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