scholarly journals Historical HbA1c Values May Explain the Type 2 Diabetes Legacy Effect: UKPDS 88

2021 ◽  
Author(s):  
Marcus Lind ◽  
Henrik Imberg ◽  
Ruth L. Coleman ◽  
Olle Nerman ◽  
Rury R. Holman
Keyword(s):  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Risk Reduction ◽  
Legacy Effects ◽  
Intensive Glucose Control ◽  
Hazard Functions ◽  
Legacy Effect ◽  
Percentage Unit ◽  
All Cause Mortality

<p><b>Objective</b> Type 2 diabetes all-cause mortality (ACM) and myocardial infarction (MI) glycaemic legacy effects have not been explained. We examined their relationships with prior individual HbA<sub>1c</sub> values and explored the potential impact of instituting earlier, compared with delayed, glucose-lowering therapy. <i></i></p> <p><b>Research design and methods</b> Twenty-year all-cause mortality (ACM) and myocardial infarction (MI) hazard functions were estimated from diagnosis of type 2 diabetes in 3,802 UK Prospective Diabetes Study participants. HbA<sub>1c</sub> values impact over time were analysed by weighting them according to their influence on downstream ACM and MI risks. </p> <p><b>Results </b>Hazard ratios for a 1 percentage unit higher HbA<sub>1c</sub> for ACM were 1.08 (95% CI 1.07-1.09), 1.18 (1.15–1.21) and 1.36 (1.30–1.42) at 5, 10 and 20 years respectively, and for MI 1.13 (1.11–1.15) at 5 years increasing to 1.31 (1.25–1.36) at 20 years. <br> Imposing a one percentage unit lower HbA<sub>1c </sub>from diagnosis generated an 18.8% (95% CI 21.1%–16.0%) ACM risk reduction 10-15 years later, whereas delaying this reduction until 10 years after diagnosis showed a 7-fold lower 2.7% (3.1%-2.3%) risk reduction. Corresponding MI risk reductions were 19.7% (22.4%-16.5%) when lowering HbA<sub>1c</sub> at diagnosis, and 3-fold lower 6.5% (7.4%-5.3%) when imposed 10 years later.</p> <p><b>Conclusions </b>The glycaemic legacy effects seen in type 2 diabetes are explained largely by historical HbA<sub>1c</sub> values having a greater impact than recent values on clinical outcomes. Early detection of diabetes and intensive glucose control from the time of diagnosis is essential to maximise reduction of the long-term risk of glycaemic complications.</p>

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 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 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.

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.

scholarly journals Metformin use and cardiovascular outcomes after acute myocardial infarction in patients with type 2 diabetes: a cohort study

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Daniel I. Bromage ◽  
Tom R. Godec ◽  
Mar Pujades-Rodriguez ◽  
Arturo Gonzalez-Izquierdo ◽  
S. Denaxas ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Acute Myocardial Infarction ◽  
Composite Endpoint ◽  
Care Hospital ◽  
Primary Care Hospital ◽  
Increased Risk ◽  
All Cause Mortality ◽  
Secondary Endpoints

Abstract Background The use of metformin after acute myocardial infarction (AMI) has been associated with reduced mortality in people with type 2 diabetes mellitus (T2DM). However, it is not known if it is acutely cardioprotective in patients taking metformin at the time of AMI. We compared patient outcomes according to metformin status at the time of admission for fatal and non-fatal AMI in a large cohort of patients in England. Methods This study used linked data from primary care, hospital admissions and death registry from 4.7 million inhabitants in England, as part of the CALIBER resource. The primary endpoint was a composite of acute myocardial infarction requiring hospitalisation, stroke and cardiovascular death. The secondary endpoints were heart failure (HF) hospitalisation and all-cause mortality. Results 4,030 patients with T2DM and incident AMI recorded between January 1998 and October 2010 were included. At AMI admission, 63.9% of patients were receiving metformin and 36.1% another oral hypoglycaemic drug. Median follow-up was 343 (IQR: 1–1436) days. Adjusted analyses showed an increased hazard of the composite endpoint in metformin users compared to non-users (HR 1.09 [1.01–1.19]), but not of the secondary endpoints. The higher risk of the composite endpoint in metformin users was only observed in people taking metformin at AMI admission, whereas metformin use post-AMI was associated with a reduction in risk of all-cause mortality (0.76 [0.62–0.93], P = 0.009). Conclusions Our study suggests that metformin use at the time of first AMI is associated with increased risk of cardiovascular disease and death in patients with T2DM, while its use post-AMI might be beneficial. Further investigation in well-designed randomised controlled trials is indicated, especially in view of emerging evidence of cardioprotection from sodium-glucose co-transporter-2 (SGLT2) inhibitors.

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