scholarly journals The cardiovascular benefits of GLP1-RA are directly related to their positive effect on glycaemic control: A meta-regression analysis

2022 ◽  
Author(s):  
Samit Ghosal ◽  
◽  
Binayak Sinha
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Control Group ◽  
Atherosclerotic Cardiovascular Disease ◽  
Population Type ◽  
Review Question ◽  
Meta Regression ◽  
Meta Regression Analysis ◽  
Positive Effect

Review question / Objective: P (patient population) = Type 2 diabetes patients with high CV risk or established atherosclerotic cardiovascular disease; I (intervention) = Received drugs: GLP1-RA; C (control group) = Compared to a control group that received a placebo; O (outcome) = Outcomes of interest included primary CV outcomes (MACE, CV death, MI, and Stroke). Condition being studied: To explore whether the heterogeneity associated with the primary outcomes benefits can be attributed to the metabolic improvements associated with GLP1-RA. The plan is to use HBA1c, weight, and SBP reduction as moderators attempting to explain any variance between the true and observed effect size.

Abstract 018: Two-year Changes of Adiponectin after Bariatric Surgery and Their Association with Incident Type 2 Diabetes, Cardiovascular Disease, Cancer and Mortality: Results from the Swedish Obese Subjects Study

Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Christian Herder ◽  
Markku Peltonen ◽  
Per-Arne Svensson ◽  
Maren Carstensen ◽  
Peter Jacobson ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Bariatric Surgery ◽  
Weight Loss ◽  
Control Group ◽  
Incident Type ◽  
Surgery Group ◽  
Obese Subjects

Introduction: Adiponectin has anti-inflammatory, insulin-sensitising and atheroprotective effects in rodents. Although serum adiponectin is uniformly downregulated in obesity, its clinical relevance in humans seems more complex. It is not known whether changes in circulating adiponectin predict type 2 diabetes, cardiovascular disease, cancer and mortality in an obese population. Hypothesis: We hypothesised that adiponectin levels are upregulated substantially after weight loss following bariatric surgery and that pronounced increases of adiponectin should offer better protection for individuals against type 2 diabetes. In addition, findings for type 2 diabetes should be compared to associations with cardiovascular disease, myocardial infarction, stroke, cancer and mortality. Methods: Serum concentrations of total adiponectin were measured in 3,223 participants of the Swedish Obese Subjects (SOS) Study (1,533 in the bariatric surgery group: 229 with gastric bypass, 1056 with vertical banded gastroplasty, 248 with adjustable gastric banding; 1,690 in the control group without surgery) at study baseline and after 2 years. Hazard ratios (HR) and 95% confidence intervals (CI) per 1 standard deviation (SD) of 2-year changes (concentration at year 2 - concentration at baseline) in adiponectin were calculated for incident type 2 diabetes, cardiovascular disease, myocardial infarction, stroke, cancer and mortality in the combined surgery group. Numbers of cases were 93, 122, 78, 55, 82 and 179, respectively. Median follow-up times ranged from 10 years for diabetes up to 16 years for mortality. Results: Mean (SD) levels of adiponectin at baseline were 7,453 (4,150) ng/ml in the combined surgery group and 8,247 (4,846) ng/ml in the control group. During the first 2 years of follow-up, adiponectin levels increased in the surgery group by 4,850 (5,387) ng/ml (parallel to a loss of 24% of body weight) and decreased slightly by 270 (2,650) ng/ml in the control group (parallel to a slight gain of 0.1% body weight). The degree of correlation between changes in adiponectin and weight loss in kg was more pronounced in the surgery groups compared with the control group (p=0.001 for interaction). Two-year increases in adiponectin in the surgery group were associated with decreased risk of type 2 diabetes (HR [95% CI] 0.61 [0.38-0.98], adjusted for baseline data for age, sex, BMI, lipids, blood pressure, alcohol consumption, smoking, anti-hypertensive drugs, glucose, insulin), but not with cardiovascular disease, myocardial infarction, stroke, cancer and mortality (adjusted HR between 0.89 and 1.05). Conclusions: Weight loss after bariatric surgery is paralleled by a substantial increase in circulating adiponectin. The degree of upregulation of adiponectin is associated with protection against future type 2 diabetes, but not with the incidence of cardiovascular outcomes, cancer or mortality.

scholarly journals Effect of Arterial Hypertension on the ICAM-1, VCAM-1 and Е-selectin Level in Type 2 Diabetes Patients

2021 ◽  
pp. 43-47
Author(s):  
Liliia Mogylnytska
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Endothelial Dysfunction ◽  
Serum Level ◽  
Control Group ◽  
Regression Equations ◽  
Multifactor Regression ◽  
Diabetes Patients

Cardiovascular disease is the leading cause of death in diabetes mellitus. Endothelial dysfunction is the first step in the development of atherosclerotic vascular lesions, which underlies cardiovascular pathology, and adhesion molecules secreted by the endothelium during inflammatory changes are involved in the progression of this lesion. The objective: the serum level of adhesive molecules (ІCAM-1, VCAM-1, Е-selectin) in hypertensive and non-hypertensive type 2 diabetes patients as a marker of endothelial dysfunction and its relationship with other risk factors for cardiovascular disease was studied. Materials and methods. We examined 64 patients with type 2 diabetes, which were divided into two subgroups: the first subgroup – 41 hypertensive type 2 diabetes patients (age – 53,56±7,14 years, BMI – 32,2±87,4; HbA1c – 9,97±2,02%), the second subgroup – 23 nonhypertensive type 2 diabetes patients (age – 50,5±4,92 years, BMI – 25,4±5,22; HbA1c – 9,09±1,95%). The control group included 18 people without diabetes with normal blood pressure (age – 50,72±6,98 years, BMI – 24,71±4,88; HbA1c – 5,26±0,42%). The serum level was determined by immunoenzyme assay. The significance of the difference between the mean values was determined by the t-Student test. Multifactor regression analysis was used to assess the relationships between the studied factors. Results. We revealed an increase of serum levels of ІCAM-1, VCAM-1, Е-selectin in hypertensive (+71,62%, +68,42%, +66,95%, respectively) and non-hypertensive type 2 diabetes patients (+46,17%, +62,79%, +42,85%, respectively) compared with the control group (p<0,01). The serum concentration of ІCAM-1, Е-selectin was higher in hypertensive type 2 diabetes patients compared to non-hypertensive type 2 diabetes patients (+17,27%, +16,86%, respectively, p<0,01). There was a significant effect of Hb1Ac, lipids, insulin resistance on the serum level of ІCAM-1, VCAM-1, Е-selectin (p<0,01). The corresponding regression equations are derived. Conclusion. There is an increase of serum level of ІCAM-1, VCAM-1, Е-selectin in hypertensive and non-hypertensive type 2 diabetes patients, which indicates the development of endothelial dysfunction. Hypertension, hyperglycemia, dyslipidemia and insulin resistance contribute to the development of these changes.

Abstract 15526: Glucagon-like Peptide-1 Receptor Agonists Reduce Adverse Cardiovascular Disease (CVD) Events in Patients With Type 2 Diabetes: An Assessment of Heterogeneity Among CVD Outcomes and a Meta-regression Analysis

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Simran Grewal ◽  
Ninad Zaman ◽  
Louis Borgatta ◽  
Matthew Nudy ◽  
Brandon Peterson
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Cardiovascular Death ◽  
Nonfatal Stroke ◽  
Significant Heterogeneity ◽  
Receptor Agonists ◽  
Meta Regression ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Introduction: Recent evidence suggests glucagon-like peptide-1 receptor agonists (GLP-1 RA) reduce adverse cardiovascular disease (CVD) events. The objective of this study is to analyze randomized controlled trials (RCTs) testing GLP-1 RA’s effects on CVD among participants with type 2 diabetes (T2DM). Methods: RCTs comparing GLP-1 RA versus placebo among participants with T2DM were identified using PubMed and Cochrane databases. The endpoints of this analysis included major adverse cardiovascular events (MACE; a composite of cardiovascular death, nonfatal myocardial infarction (MI), and nonfatal stroke), and the individual components of MACE. The primary analysis calculated risk ratios (RR) and 95% confidence intervals (CI) for each endpoint. Heterogeneity for each endpoint was calculated using Chi 2 and I 2 tests. For any endpoint with significant heterogeneity, a meta-regression was performed using baseline hemoglobin A1C (A1C) in each RCT as the moderator and a R 2 value was calculated. Results: 7 RCTs (N = 56,004) were identified with 174,163 patient years of follow-up. GLP-1 RA reduced MACE [RR 0.89, 95% CI 0.83-0.95], cardiovascular death [RR 0.88, 95% CI 0.81-0.95], and nonfatal stroke [RR 0.85, 95% CI 0.77-0.94]. There was no significant heterogeneity among these RCTs (Figure 1). GLP-1 RA did not reduce nonfatal MI [RR 0.91, 95% CI 0.82-1.02]. However, there was significant heterogeneity among these RCTS (Chi 2 =12.94, p=0.04, I 2 =54%). When accounting for A1C in the regression model, there was no longer significant heterogeneity for this endpoint (p=0.23, I 2 =27%). A relationship between A1C and GLP-1 RA’s effect on nonfatal MI (R 2 =0.64, Figure 1) was observed when performing the meta-regression. Conclusion: GLP-1 RA reduced MACE, cardiovascular death, and nonfatal stroke in patients with T2DM with minimal heterogeneity among RCTs. GLP-1 RA did not reduce nonfatal MI, however there may be an association between A1C and GLP-1 RA’s effect on nonfatal MI.

Abstract 15004: Bariatric Surgery is Associated With Reduced Atherosclerotic Cardiovascular Disease Burden in Obese Patients With Type 2 Diabetes: A Propensity-matched Cohort Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Francesca Watson ◽  
Maddalena Ardissino ◽  
Ravi J Amin ◽  
Chanpreet Arhi ◽  
Peter Collins ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Bariatric Surgery ◽  
Disease Burden ◽  
Atherosclerotic Cardiovascular Disease ◽  
Obese Patients ◽  
Matched Cohort ◽  
All Cause Mortality

Introduction: Obesity is an increasingly prevalent global health issue and has a considerable disease burden, including numerous co-morbidities. Atherosclerotic cardiovascular disease (ASCVD) is one such co-morbidity associated with a high mortality rate and prevalence, especially in patients with obesity and concomitant Type 2 diabetes mellitus (T2DM). Bariatric surgery is an effective intervention for patients with obesity, shown to reduce overall cardiovascular disease risk. However, few studies have quantified the long-term impact of bariatric surgery on ASCVD outcomes in the context of key co-morbidities such as T2DM. Hypothesis: Bariatric surgery will improve long-term ASCVD outcomes in obese patients with T2DM. Methods: A nested, nationwide, propensity-matched cohort study was carried out using the Clinical Practice Research Datalink. The study cohort included 593 patients who underwent bariatric surgery and had no past history of ASCVD. A further 593 patients served as propensity-score matched controls. Patients were followed up for a median time of 47.2 months. The primary composite study endpoint was the incidence of ASCVD defined by a diagnosis of new coronary artery disease (CAD), cerebrovascular disease (CeVD), peripheral arterial disease (PAD), or other miscellaneous atherosclerotic disease. Secondary endpoints included all-cause mortality and the incidence of CAD, CeVD, and PAD individually. Results: Patients who underwent bariatric surgery had significantly lower rates of new ASCVD during follow-up (HR 0.53, CI 0.30-0.95, p=0.032). No significant difference was observed in rates of new CAD (HR 0.69, CI 0.32-1.46, p=0.331), CeVD (HR 0.23, CI 0.00-5.45, p=0.1760) and PAD (HR 0.55, CI 0.21-1.43, p=0.218). The bariatric surgery group also had a lower rate of all-cause mortality (HR 0.36, CI 0.19-0.71, p=0.003) compared to controls. Conclusions: In this study, bariatric surgery was associated with improved ASCVD outcomes, as well as lower all-cause mortality, in patients with obesity and T2DM. These findings support the use of bariatric surgery in treating obesity and reducing the burden of its related comorbidities.

scholarly journals Alirocumab therapy in individuals with type 2 diabetes mellitus and atherosclerotic cardiovascular disease: analysis of the ODYSSEY DM-DYSLIPIDEMIA and DM-INSULIN studies

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Kausik K. Ray ◽  
Stefano Del Prato ◽  
Dirk Müller-Wieland ◽  
Bertrand Cariou ◽  
Helen M. Colhoun ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cardiovascular Disease ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Lipoprotein Cholesterol ◽  
Atherosclerotic Cardiovascular Disease ◽  
Open Label ◽  
Double Blind ◽  
Mixed Dyslipidemia

Abstract Background Individuals with diabetes often have high levels of atherogenic lipoproteins and cholesterol reflected by elevated low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C), apolipoprotein B (ApoB), and LDL particle number (LDL-PN). The presence of atherosclerotic cardiovascular disease (ASCVD) increases the risk of future cardiovascular events. We evaluated the efficacy and safety of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, alirocumab, among individuals with type 2 diabetes (T2DM), high LDL-C or non-HDL-C, and established ASCVD receiving maximally tolerated statin in ODYSSEY DM-DYSLIPIDEMIA (NCT02642159) and DM-INSULIN (NCT02585778). Methods In DM-DYSLIPIDEMIA, individuals with T2DM and mixed dyslipidemia (non-HDL-C ≥ 100 mg/dL; n = 413) were randomized to open-label alirocumab 75 mg every 2 weeks (Q2W) or usual care (UC) for 24 weeks, with UC options selected before stratified randomization. In DM-INSULIN, insulin-treated individuals with T2DM (LDL-C ≥ 70 mg/dL; n = 441) were randomized in a double-blind fashion to alirocumab 75 mg Q2W or placebo for 24 weeks. Study participants also had a glycated hemoglobin < 9% (DM-DYSLIPIDEMIA) or < 10% (DM-INSULIN). Alirocumab dose was increased to 150 mg Q2W at week 12 if week 8 LDL-C was ≥ 70 mg/dL (DM-INSULIN) or non-HDL-C was ≥ 100 mg/dL (DM-DYSLIPIDEMIA). Lipid reductions and safety were assessed in patients with ASCVD from these studies. Results This analysis included 142 DM-DYSLIPIDEMIA and 177 DM-INSULIN participants with ASCVD, including 95.1% and 86.4% with coronary heart disease, and 32.4% and 49.7% with microvascular diabetes complications, respectively. At week 24, alirocumab significantly reduced LDL-C, non-HDL-C, ApoB, and LDL-PN from baseline versus control. This translated into a greater proportion of individuals achieving non-HDL-C < 100 mg/dL (64.6% alirocumab/23.8% UC [DM-DYSLIPIDEMIA]; 65.4% alirocumab/14.9% placebo [DM-INSULIN]) and ApoB < 80 mg/dL (75.1% alirocumab/35.4% UC and 76.8% alirocumab/24.8% placebo, respectively) versus control at week 24 (all P < 0.0001). In pooling these studies, 66.4% (alirocumab) and 67.0% (control) of individuals reported treatment-emergent adverse events. The adverse event pattern was similar with alirocumab versus controls. Conclusions Among individuals with T2DM and ASCVD who had high non-HDL-C/LDL-C levels despite maximally tolerated statin, alirocumab significantly reduced atherogenic cholesterol and LDL-PN versus control. Alirocumab was generally well tolerated. Trial registration Clinicaltrials.gov. NCT02642159. Registered 30 December 2015 and Clinicaltrials.gov. NCT02585778. Registered 23 October 2015

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