Pediatric Atorvastatin in Diabetes Trial (PADIT): a pilot study to determine the effect of atorvastatin on arterial stiffness and endothelial function in children with type 1 diabetes mellitus.
Ontology highlight
ABSTRACT:
SUBMITTER: Haller MJ
PROVIDER: S-EPMC3621084 | biostudies-literature | 2009 Jan
REPOSITORIES: biostudies-literature
Publications
Pediatric Atorvastatin in Diabetes Trial (PADIT): a pilot study to determine the effect of atorvastatin on arterial stiffness and endothelial function in children with type 1 diabetes mellitus.
Haller Michael J MJ Stein Jennifer M JM Shuster Jonathan J JJ Theriaque Douglas D Samyn Margaret M MM Pepine Carl C Silverstein Janet H JH
Journal of pediatric endocrinology & metabolism : JPEM 20090101 1
Fifty-one children with type 1 diabetes mellitus (DM1) participated in a double blinded, randomized, cross-over pilot study to determine whether 12 weeks of daily atorvastatin (20 mg daily) would reduce arterial stiffness and improve endothelial function. Secondary analysis demonstrated potential reduction of arterial stiffness following atorvastatin therapy (p = 0.06). Additional long-term prospective studies with larger numbers of patients are needed. ...[more]
Similar Datasets
Project description:BackgroundIt is uncertain whether saturated fatty acids (SFAs) impair endothelial function and contribute to arterial stiffening.ObjectiveWe tested the effects of replacing SFAs with monounsaturated fatty acids (MUFAs) or carbohydrates on endothelial function and arterial stiffness.DesignWith the use of a parallel-designed randomized controlled trial in 121 insulin-resistant men and women, we measured vascular function after 1 mo of consumption of a high-SFA (HS) diet and after 24 wk after random assignment to the HS diet or diets that contained <10% SFAs and were high in either MUFAs or carbohydrates. The primary outcome was a change in flow-mediated dilation (FMD), and secondary outcomes were changes in carotid to femoral pulse wave velocity (PWV) and plasma 8-isoprostane F2?-III concentrations.ResultsFor 112 participants with data available for analysis on the specified outcomes, no significant differences were shown. FMD with the HS reference diet was 6.7 ± 2.2%, and changes (95% CIs) after 6 mo of intervention were +0.3 (-0.4, 1.1), -0.2 (-0.8, 0.5), and -0.1 (-0.6, 0.7) with HS, high-MUFA (HM), and high-carbohydrate (HC) diets, respectively. After consumption of the HS reference diet, the geometric mean (±SD) PWV was 7.67 ± 1.62 m/s, and mean percentages of changes (95% CIs) were -1.0 (-6.2, 4.3) with the HS diet, 2.7 (-1.4, 6.9) with the HM diet, and -1.0 (-5.5, 3.4) with the HC diet. With the HS reference diet, the geometric mean (±SD) plasma 8-isoprostane F2?-III concentration was 176 ± 85 pmol/L, and mean percentage of changes (95% CIs) were 1 (-12, 14) with the HS diet, 6 (-5, 16) with the HM diet, and 4 (-7, 16) with the HC diet.ConclusionThe replacement of SFAs with MUFAs or carbohydrates in healthy subjects does not affect vascular function. This trial was registered at Current Controlled Trials (http://www.controlled-trials.com/ISRCTN) as ISRCTN 29111298.
| S-EPMC3743730 | biostudies-literature
Project description:IntroductionBrachial-ankle pulse wave velocity (baPWV), an indicator of arterial stiffness, has been demonstrated to be associated with type 2 diabetes mellitus (T2DM) and its vascular complications. This study was aimed at investigating the correlations of baPWV with both the presence and severity of diabetic retinopathy (DR) at baseline and at exploring the predictive role of baPWV in the new onset/progression of DR in the follow-up analysis.MethodsThe prospective cohort study recruited 2,473 Chinese patients with T2DM, of whom 663 participants were finally included in the follow-up analysis. The presence and grading of DR were performed by the modified Early Treatment Diabetic Retinopathy Study. Uni- or multivariate linear and logistic regression models and Cox proportional-hazards regression analysis were conducted.ResultsOf 2,473 patients with T2DM at baseline, 734 individuals were assessed to have DR and further categorized into 630 with non-sight-threatening DR (NSTDR) and 104 with STDR. In addition to the positive relationship between increased baPWV and the presence of DR, multinominal logistic regression analysis revealed that higher tertiles of baPWV were significantly related to the NSTDR (T2: OR = 1.62 (1.22, 2.15), p < 0.001, and T3: OR = 2.58 (1.86, 3.58), p < 0.001) and STDR group (T3: OR = 3.87 (1.87, 8.02), p < 0.001). During a follow-up (mean period of 16.4 months), 111 participants had new onset/progression of DR. The cox regressions showed that high baseline baPWV was correlated with increased risk of development/progression of DR (HR = 2.24, 95% CI (1.24, 4.03), p = 0.007, for T2 baPWV and HR = 2.90, 95% CI (1.49, 5.64), p = 0.002, for T3 baPWV) after adjustments for multiple factors.ConclusionsOur results demonstrated that baseline baPWV might be an independent predictor in new onset/worsening of DR, suggesting that increased arterial stiffness might be involved in the development of DR. Follow-up studies with a longer duration are needed.
| S-EPMC8486550 | biostudies-literature
Project description:IntroductionMagnesium (Mg) may protect against arterial calcification. We tested the hypotheses that a higher serum Mg concentration is associated with less arterial calcification and stiffness in patients on hemodialysis (HD) and that these associations are modified by diabetes mellitus.MethodsWe performed cross-sectional analyses of 367 incident HD patients from the Predictors of Arrhythmic and Cardiovascular Risk in End Stage Renal Disease (PACE) cohort. Measures of arterial calcification and stiffness included coronary arterial calcification (CAC) and thoracic aortic calcification (TAC) scores, ankle brachial index (ABI; high ABI: >1.4 or incompressible vessels), pulse wave velocity (PWV), and pulse pressure.ResultsMean Mg was 1.8 ± 0.2 mEq/l and 58% had diabetes. Among nondiabetic individuals, per 0.1 mEq/l higher Mg, non-zero CAC score was lower (% difference: -15.4%; 95% confidence interval [CI]: -28% to -0.55%; P = 0.03), the odds of having TAC score >0 and the odds of having high ABI were lower (odds ratio [OR]: 0.66; 95% CI 0.47-0.93; P = 0.02, and 0.23; 95% CI: 0.06-0.83, P = 0.03, respectively) while adjusting for demographics, comorbidities, markers of mineral metabolism, and dialysis clearance. Among diabetic individuals, per 0.1 mEq/l higher Mg, the odds of having TAC score >0 was higher (OR: 1.57; 95% CI: 1.09-2.26; P = 0.02). Mg was not associated with CAC or high ABI among diabetic individuals. Mg was not associated with PWV or pulse pressure regardless of diabetes status.ConclusionDiabetes modified the associations of serum Mg with arterial calcification and stiffness in incident HD patients. Higher Mg was associated with less arterial calcification and less peripheral arterial stiffness among nondiabetic individuals, but Mg was only associated with TAC among diabetic individuals with higher Mg being associated with higher likelihood of having TAC score >0.
| S-EPMC6551514 | biostudies-literature
Project description:Individuals with type 1 diabetes mellitus are at high risk for the development of hypertension, contributing to cardiovascular complications. Hyperglycaemia-mediated neurohormonal activation increases arterial stiffness, and is an important contributing factor for hypertension. Since the sodium glucose cotransport-2 (SGLT2) inhibitor empagliflozin lowers blood pressure and HbA1c in type 1 diabetes mellitus, we hypothesized that this agent would also reduce arterial stiffness and markers of sympathetic nervous system activity.Blood pressure, arterial stiffness, heart rate variability (HRV) and circulating adrenergic mediators were measured during clamped euglycaemia (blood glucose 4-6 mmol/L) and hyperglycaemia (blood glucose 9-11 mmol/L) in 40 normotensive type 1 diabetes mellitus patients. Studies were repeated after 8 weeks of empagliflozin (25 mg once daily).In response to empagliflozin during clamped euglycaemia, systolic blood pressure (111 ± 9 to 109 ± 9 mmHg, p?=?0.02) and augmentation indices at the radial (-52% ± 16 to -57% ± 17, p?=?0.0001), carotid (+1.3 ± 1 7.0 to -5.7 ± 17.0%, p?<?0.0001) and aortic positions (+0.1 ± 13.4 to -6.2 ± 14.3%, p?<?0.0001) declined. Similar effects on arterial stiffness were observed during clamped hyperglycaemia without changing blood pressure under this condition. Carotid-radial pulse wave velocity decreased significantly under both glycemic conditions (p???0.0001), while declines in carotid-femoral pulse wave velocity were only significant during clamped hyperglycaemia (5.7 ± 1.1 to 5.2 ± 0.9 m/s, p?=?0.0017). HRV, plasma noradrenalin and adrenaline remained unchanged under both clamped euglycemic and hyperglycemic conditions.Empagliflozin is associated with a decline in arterial stiffness in young type 1 diabetes mellitus subjects. The underlying mechanisms may relate to pleiotropic actions of SGLT2 inhibition, including glucose lowering, antihypertensive and weight reduction effects.NCT01392560.
| S-EPMC3915232 | biostudies-literature
Project description:BackgroundEmpagliflozin has been shown to reduce cardiovascular mortality, but the underlying pathogenetic mechanisms are poorly understood. It was previously demonstrated that empagliflozin improved arterial stiffness.MethodsOur analysis comprising 58 patients with type 2 diabetes mellitus identifies factors triggering the improvement of arterial stiffness. All patients participated in an investigator-initiated, prospective, double-blind, randomized, placebo-controlled, interventional clinical trial ( http://www.ClinicalTrials.gov : NCT02471963, registered 15th June 2015, retrospectively registered) and received either 6-weeks treatment with 25 mg empagliflozin orally once daily or placebo (crossover). Central systolic pressure and central pulse pressure were recorded by the SphygmoCor System (AtCor Medical). Now, we investigated the impact of parameters of glucose metabolism, volume status, sympathetic activation, lipids, uric acid, blood pressure and inflammation on vascular parameters of arterial stiffness using multivariate regression analysis.ResultsAs previously reported, therapy with empagliflozin improved arterial stiffness as indicated by reduced central systolic blood pressure (113.6 ± 12.1 vs 118.6 ± 12.9 mmHg, p < 0.001), central pulse pressure (39.1 ± 10.2 vs 41.9 ± 10.7 mmHg, p = 0.027) forward (27.1 ± 5.69 vs 28.7 ± 6.23 mmHg, p = 0.031) as well as reflected wave amplitude (18.9 ± 5.98 vs 20.3 ± 5.97 mmHg, p = 0.045) compared to placebo. The multivariate regression analysis included age, sex and change between empagliflozin and placebo therapy of the following parameters: HbA1c, copeptin, hematocrit, heart rate, LDL-cholesterol, uric acid, systolic 24-h ambulatory blood pressure and high sensitive CRP (hsCRP). Besides the influence of age (beta = - 0.259, p = 0.054), sex (beta = 0.292, p = 0.040) and change in systolic 24-h ambulatory blood pressure (beta = 0.364, p = 0.019), the change of hsCRP (beta = 0.305, p = 0.033) emerged as a significant determinant of the empagliflozin induced reduction in arterial stiffness (placebo corrected). When replacing HbA1c with fasting plasma glucose in the multivariate regression analysis, a similar effect of the change in hsCRP (beta = 0.347, p = 0.017) on arterial stiffness parameters was found.ConclusionBesides age and sex, change in systolic 24-h ambulatory blood pressure and change in hsCRP were determinants of the empagliflozin induced improvement of vascular parameters of arterial stiffness, whereas parameters of change in glucose metabolism and volume status had no significant influence. Our analysis suggests that empagliflozin exerts, at least to some extent, its beneficial vascular effects via anti-inflammatory mechanisms. Trial registration http://www.ClinicalTrials.gov : NCT02471963, registered 15th June 2015, retrospectively registered.
| S-EPMC6440009 | biostudies-literature
Project description:BackgroundIn older adults, an independent association exists between impaired lung function and cardiovascular disease. This interaction might be related to the effects of aging and/or smoking. In order to explore possible childhood antecedents to this association, we hypothesized that decreased lung function and vascular stiffness might be related, in early life.ObjectiveTo determine the relationship between lung function and carotid augmentation index (AIx), a measure of vascular stiffness, in 8-year old children.MethodsData on brachial blood pressure, lung function (FEV(1), FVC, FEV(1)/FVC, obtained by spirometry) and carotid AIx75 (AIx standardised to an arbitrary heart rate of 75 beats per minute, obtained by applanation tonometry) was available in 249 community-based 8-year old children. These healthy children had been subjects in a randomised controlled trial of two interventions (omega-3 fatty acid supplementation and house-dust mite avoidance) to prevent asthma. Smoking in pregnancy and childhood environmental tobacco smoke (ETS) exposure was prospectively collected by questionnaire. The association between lung function and carotid AIx75 was assessed in multivariate models that included sex, height, smoking status during pregnancy, ETS exposure and randomisation groups (house dust mite avoidance and dietary intervention) as covariates.ResultsIn the fully adjusted models, Carotid AIx75 was independently associated with FEV1 (standardised β = -0.17,b = -6.72, partial R(2) = .02, p = 0.03), FVC (standardised β = -0.29, b = -9.31, partial R(2) = 0.04, p<0.001) and FEV1/FVC (standardised β = .13, b = 18.4, partial R(2) = 0.02, p = 0.04).ConclusionLower lung volumes are associated with increased vascular stiffness at an early age. The interaction between lung function and vascular stiffness may thus represent more than just age-related alterations in both the pulmonary and vascular systems.
| S-EPMC3201952 | biostudies-literature
Project description:BACKGROUND:P-selectin, encoded by SELP, has been implicated as an important molecule in the development of arterial stiffness, consequently leading to vascular complications in T2DM. SELP polymorphisms and increased levels of soluble P-selectin (sP-selectin) have been shown to be associated with several inflammatory diseases. The present work was designed to assess nine putative functional non-coding SELP variants in relation to sP-selectin levels and arterial stiffness in T2DM. METHODS:The genetic distribution of rs3917655, rs3917657, rs3917739, rs2235302, rs3917843 was determined by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR). Genotyping of rs3917779 was performed by tetra primer amplification-refractory mutation system (ARMS)- PCR. Three SNPs i.e. rs3917853, rs3917854, rs3917855 were genotyped by Sanger sequencing. Construction of haplotypes was performed using PHASE software. The data thus obtained was analyzed by appropriate statistical tools. RESULTS:Two non-coding variants i.e. rs3917657 and rs3917854 of SELP were found to be associated with 2 and 1.7 -fold risk of disease development respectively. However, one non-coding variant rs2235302 was found to provide protection against disease development. Furthermore, variant allele of rs3917854 in T2DM patients was found to be associated with 2.07-fold very high vascular risk. Non-coding haplotype GCAGGCCGC was conferring 4.14-fold risk of disease development. Furthermore, overall sP-selectin levels were higher in T2DM patients when segregated according to genotypes as well as haplotypes. Significant genotype- phenotype correlation was observed for rs3917655 as well as rs3917739 variant in patients and for rs3917854 in controls. In vascular risk categories, a significant genotype- phenotype correlation was observed for rs3917655 and rs2235302. Furthermore, patients with CCGGGCCGC haplotype in high risk category were observed with higher levels of sP-selectin as compared to other haplotypes (p?<?0.05). CONCLUSIONS:Non-coding SELP variants may significantly modulate sP-selectin levels, vascular risk and T2DM susceptibility.
| S-EPMC7236446 | biostudies-literature
Project description:OBJECTIVE:The aim of this study was to investigate the endothelial protein C receptor (EPCR) gene A3 haplotype and plasma soluble EPCR (sEPCR) levels in Turkish pediatric arterial stroke patients. MATERIALS AND METHODS:We analyzed 44 pediatric arterial stroke patients and 75 healthy controls. Following DNA isolation, genotyping of the A3 haplotype was determined via PCR and RFLP. Additionally, fasting sEPCR levels were determined via ELISA. RESULTS:There wasn't a significant difference in the sEPCR level between the control and patient groups, although the sEPCR level was higher in the patient group. We didn't observe a difference in the distribution of the CC and CG/GG genotypes between the control and patient groups. CONCLUSION:Further study on sEPCR levels at the onset of pediatric stroke is needed in order to reach a more definitive conclusion. CONFLICT OF INTEREST:None declared.
| S-EPMC3781647 | biostudies-literature
Project description:Background The incidence of type 1 diabetes mellitus (T1DM) in children is increasing, resulting in higher burden of cardiovascular diseases due to diabetes mellitus-related vascular dysfunction. Methods and Results We examined cardiovascular risk factors ( CVRF s) and arterial parameters in 1809 youth with T1DM. Demographics, anthropometrics, blood pressure, and laboratory data were collected at T1DM onset and 5 years later. Pulse wave velocity and augmentation index were collected with tonometry. ANOVA or chi-square tests were used to test for differences in measures of arterial parameters by CVRF . Area under the curve of CVRF s was entered in general linear models to explore determinants of accelerate vascular aging. Participants at the time of arterial measurement were 17.6±4.5 years old, 50% female, 76% non-Hispanic white, and duration of T1DM was 7.8±1.9 years. Glycemic control was poor (glycated hemoglobin, 9.1±1.8%). All arterial parameters were higher in participants with glycated hemoglobin ≥9% and pulse wave velocity was higher with lower insulin sensitivity or longer duration of diabetes mellitus. Differences in arterial parameters were found by sex, age, and presence of obesity, hypertension, or dyslipidemia. In multivariable models, higher glycated hemoglobin, lower insulin sensitivity, body mass index, blood pressure, and lipid areas under the curve were associated with accelerated vascular aging. Conclusions In young people with T1DM, persistent poor glycemic control and higher levels of traditional CVRF s are independently associated with arterial aging. Improving glycemic control and interventions to lower CVRF s may prevent future cardiovascular events in young individuals with T1DM.
| S-EPMC6662363 | biostudies-literature
Project description:AimsTo investigate synergistic effects of liver fibrosis evaluated by FibroScan and sarcopenia on endothelial function and arterial stiffness in patients with type 2 diabetes.MethodsThis cross-sectional study evaluated liver fibrosis (LF) and sarcopenia in 115 patients with type 2 diabetes. LF was assessed as the liver stiffness measurement (LSM) in transient elastography (FibroScan) and was defined as an LSM greater than or equal to 8.0 kPa. Sarcopenia was defined as a ratio of appendicula skeletal muscle mass to body mass index of<0.789 in men and<0.512 in women. Endothelial function was measured by reactive hyperemia index (RHI) with tonometry, and arterial stiffness was evaluated by the cardio-ankle vascular index (CAVI). Endothelial dysfunction was defined an RHI value below 1.67, while arterial stiffness was defined a CAVI value above 9.0. Patients were divided into four groups: no LF and no sarcopenia; LF but no sarcopenia; no LF but sarcopenia; and LF and sarcopenia. The composite of endothelial dysfunction of arterial stiffness was defined as an outcome.ResultsIn patients with LF, RHI was significantly lower and CAVI was significantly higher than in patients without LF. Furthermore, RHI was significantly lower in patients with sarcopenia than in those without it. Patients with both LF and sarcopenia had the lowest RHI and the highest CAVI and urinary albumin levels. Sarcopenia and HDL cholesterol were independent factor the composite of endothelial dysfunction and arterial stiffness.ConclusionLF and sarcopenia are independently associated with endothelial dysfunction and arterial stiffness in patients with type 2 diabetes. Coexistence of LF and sarcopenia may synergistically lead to vascular damage and thus contribute to the high risk of cardiovascular disease in people with type 2 diabetes.
| S-EPMC9213220 | biostudies-literature