The effects of linagliptin on endothelial function and global arginine bioavailability ratio in coronary artery disease patients with early diabetes: study protocol for a randomized controlled trial

Tripolt, Norbert J.; Aberer, Felix; Riedl, Regina; Hutz, Barbara; Url, Jasmin; Dimsity, Gudrun; Meinitzer, Andreas; Stojaković, Tatjana; Hödl, Ronald; Brodmann, Marianne; Hafner, Franz; Sourij, Harald

doi:10.1186/s13063-016-1627-3

Cited by 6 publications

(4 citation statements)

References 22 publications

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“…Detailed information regarding the design and methods of this study were described previously [ 15 ]. Briefly, patients with early T2DM and manifest coronary atherosclerosis (diagnosed either by coronary angiography or coronary computer tomography), aged between 40 and 80 years, with either a 2 h-glucose value above 200 mg/dl after 75 g glucose load or a glycated haemoglobin (HbA1c) level between 42 and 75 mmol/mol while on diet only or metformin monotherapy, were included in the trial.…”

Section: Methodsmentioning

confidence: 99%

Effects of linagliptin on endothelial function and postprandial lipids in coronary artery disease patients with early diabetes: a randomized, placebo-controlled, double-blind trial

Tripolt

Aberer

Riedl

et al. 2018

Cardiovasc Diabetol

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BackgroundEarly glucose lowering intervention in subjects with type 2 diabetes mellitus was demonstrated to be beneficial in terms of micro- and macrovascular risk reduction. However, most of currently ongoing cardiovascular outcome trials are performed in subjects with manifest atherosclerosis and long-standing diabetes. Therefore, the aim of this study is to investigate the effects of the dipeptidylpeptidase-4 inhibitor linagliptin in subjects with coronary artery disease (CAD) but early type 2 diabetes mellitus (T2DM) on a set of cardiovascular surrogate measurements.MethodsIn this randomized, placebo-controlled, double-blind, single-center study, we included subjects with early diabetes (postchallenge diabetes (2 h glucose > 200 mg/dl) or T2DM treated with diet only or on a stable dose of metformin monotherapy and an HbA1c < 75 mmol/mol) and established CAD. Participants were randomized to receive either linagliptin (5 mg) once daily orally or placebo for 12 weeks. The primary outcome was the change in flow mediated dilatation (FMD). The secondary objective was to investigate the effect of linagliptin treatment on arginine bioavailability ratios [Global arginine bioavailability ratio (GABR) and arginine to ornithine ratio (AOR)]. Arginine, ornithine and citrulline were measured in serum samples with a conventional usual amino acid analysis technique, involving separation of amino acids by ion exchange chromatography followed by postcolumn continuous reaction with ninhydrin. GABR was calculated by l-arginine divided by the sum of (l-ornithine plus l-citrulline). The AOR was calculated by dividing l-arginine by l-ornithine levels. Group comparisons were calculated by using a two-sample t-test with Satterthwaite adjustment for unequal variances.ResultsWe investigated 43 patients (21% female) with a mean age of 63.3 ± 8.2 years. FMD at baseline was 3.5 ± 3.1% in the linagliptin group vs. 4.0 ± 2.9% in the placebo group. The change in mean FMD in the linagliptin group was not significantly different compared to the change in the placebo group (0.43 ± 4.84% vs. − 0.45 ± 3.01%; p = 0.486). No significant improvements were seen in the arginine bioavailability ratios (GABR; p = 0.608 and AOR; p = 0.549).ConclusionLinagliptin treatment in subjects with CAD and early T2DM did not improve endothelial function or the arginine bioavailability ratios.Trial registration ClinicalTrials.gov, NCT02350478 (https://clinicaltrials.gov/ct2/show/NCT02350478)Electronic supplementary materialThe online version of this article (10.1186/s12933-018-0716-x) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

Effects of linagliptin on endothelial function and postprandial lipids in coronary artery disease patients with early diabetes: a randomized, placebo-controlled, double-blind trial

Tripolt

Aberer

Riedl

et al. 2018

Cardiovasc Diabetol

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“…In addition, patients with CHD and EBG are at a higher risk of nephropathy and other cardiovascular diseases. CHD complicated with diabetes is associated with decreased insulin sensitivity, impaired blood pressure regulation, damaged vascular endothelial cells and dysfunction of the fibrinolytic system ( 10 , 11 ). Lowering blood sugar is extremely important to improve prognosis and prevent the onset of cardiovascular diseases ( 12 – 14 ).…”

Section: Introductionmentioning

confidence: 99%

Impaired Sensitivity to Thyroid Hormones Is Associated With Elevated Blood Glucose in Coronary Heart Disease

Yang

et al. 2022

Front. Endocrinol.

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ContextThyroid hormones influence glucose homeostasis through central and peripheral regulation. To date, the association between thyroid hormone sensitivity and elevated blood glucose (EBG) in patients with coronary heart disease (CHD) remains unknown. The purpose of this study was to investigate the association between thyroid hormone sensitivity and risk of EBG in patients with CHD, and to further explore their association in different sexes and ages.MethodsThis large multicenter retrospective study included 30,244 patients with CHD (aged 30–80 years) between 1 January 2014 and 30 September 2020. Parameters representing central and peripheral sensitivity to thyroid hormones were calculated. Central sensitivity to thyroid hormones was assessed by calculating the Thyroid Feedback Quantile-based Index (TFQI), Thyroid-stimulating Hormone Index (TSHI), and Thyrotropin Thyroxine Resistance Index (TT4RI), and Parametric Thyroid Feedback Quantile-based Index (PTFQI); peripheral sensitivity to thyroid hormones was evaluated using the ratio of free triiodothyronine (FT3) /free thyroxine (FT4). Taking normal glucose tolerance (NGT) as a reference, logistic regression was used to analyse the relationship between central and peripheral thyroid hormone sensitivity and EBG in patients with CHD.ResultsAmong the 30,244 participants, 15,493 (51.23%) had EBG. The risk of EBG was negatively correlated with TSHI (OR: 0.91; 95%CI: 0.91 to 0.92; P < 0.001), TT4RI (OR: 0.99; 95% CI: 0.99 to 0.99; P<0.001), TFQI (OR: 0.82; 95%CI: 0.80 to 0.84; P <0.001) and PTFQI (OR: 0.76; 95%CI: 0.74 to 0.78; P<0.001). Compared to males and patients aged 60 and below, the OR value for EBG was lower in females and in patients aged over 60 years old. Conversely, EBG risk was positively associated with FT3/FT4 (OR: 1.08; 95% CI: 1.07 to 1.09; P <0.001) and in the sex-categorized subgroups, males had higher OR values than females.ConclusionsThis study showed that thyroid hormone sensitivity is significantly associated with EBG in patients with CHD. This association is higher in females than in males, and the association in those aged over 60 years old is higher than that in patients aged 60 years and below.

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“…Elevated blood glucose, insulin resistance and inflammation marker lnt of simple coronary heart disease (CHD) or diabetes mellitus type 2 (T2DM) ( 1 ), which, in turn, also affect the body's fat metabolism, blood pressure regulation and glucose metabolism process ( 2 ). T2DM and CHD are associated with decreased sensitivity to insulin, weakened blood pressure regulation ability ( 3 ), damaged vascular endothelial cells, dysfunction of the fibrinolytic system ( 4 ), and enhancement of the inflammatory responses ( 5 ). However, the way in which these factors interact with each other to result in either or both diseases is not clear.…”

Section: Introductionmentioning

confidence: 99%

Insulin resistance, blood glucose and inflammatory cytokine levels are risk factors for cardiovascular events in diabetic patients complicated with coronary heart disease

Wang

Guo

et al. 2017

Exp Ther Med

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This study was designed to investigate the relation of insulin resistance, blood glucose and inflammatory cytokines with cardiovascular events in diabetic patients complicated with coronary heart disease (CHD). A total of 120 patients with diabetes mellitus type 2 (T2DM) complicated with CHD admitted to Jinan Central Hospital from January 2015 to March 2016 were enrolled in this study. There were 60 cases complicated with cardiovascular events and 60 had no history of cardiovascular events; there were 40 cases with abnormal blood glucose, 40 with insulin resistance and 40 with elevated inflammatory cytokines. Changes in the levels of blood glucose, fasting serum insulin and inflammatory cytokines as well as changes in the homeostasis model assessment of insulin resistance indexes (HOMA-IR) were recorded and compared among groups of patients. Besides, changes in the Global Registry of Acute Coronary Events (GRACE) risk score and the incidence rate of cardiovascular events were also detected and multivariate logistic regression analysis was conducted so as to identify relevant risk factors. Our results showed the fasting blood glucose and the 2 h postprandial blood glucose levels in the non-cardiovascular event group were lower than those in the cardiovascular event group (P<0.05). However, levels of fasting serum insulin and HOMA-IR in the non-cardiovascular event group were significantly higher than those in the cardiovascular event group (P<0.05). Additionally, levels of tumor necrosis factor-α (TNF-α), interleukin-6 and C-reactive protein in the non-cardiovascular event group were significantly lower than those in the cardiovascular event group (P<0.05). Moreover, GRACE risk scores in patients with elevated inflammatory cytokines were higher than those in patients with insulin resistance and those in patients with blood glucose abnormalities (P<0.05). The incidence rate of cardiovascular events in patients with blood glucose abnormalities was lower than that in patients with insulin resistance and that in patients with elevated inflammatory cytokines. There was a positive correlation between TNF-α and HOMA-IR (P<0.05), and between HOMA-IR and the GRACE risk score (P<0.05). Blood glucose abnormalities, insulin resistance and inflammatory cytokines were all independent risk factors for cardiovascular events. Based on our findings, stronger inflammatory responses in patients with T2DM complicated with CHD lead to higher incidence rates of cardiovascular events. Besides that, elevated blood glucose and insulin resistance levels are also independent risk factors for cardiovascular events.

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The effects of linagliptin on endothelial function and global arginine bioavailability ratio in coronary artery disease patients with early diabetes: study protocol for a randomized controlled trial

Cited by 6 publications

References 22 publications

Effects of linagliptin on endothelial function and postprandial lipids in coronary artery disease patients with early diabetes: a randomized, placebo-controlled, double-blind trial

Effects of linagliptin on endothelial function and postprandial lipids in coronary artery disease patients with early diabetes: a randomized, placebo-controlled, double-blind trial

Impaired Sensitivity to Thyroid Hormones Is Associated With Elevated Blood Glucose in Coronary Heart Disease

Insulin resistance, blood glucose and inflammatory cytokine levels are risk factors for cardiovascular events in diabetic patients complicated with coronary heart disease

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