Liraglutide decreases carotid intima-media thickness in patients with type 2 diabetes: 8-month prospective pilot study.
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ABSTRACT:
SUBMITTER: Rizzo M
PROVIDER: S-EPMC3948058 | biostudies-literature | 2014 Feb
REPOSITORIES: biostudies-literature
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Liraglutide decreases carotid intima-media thickness in patients with type 2 diabetes: 8-month prospective pilot study.
Rizzo Manfredi M Chandalia Manisha M Patti Angelo Maria AM Di Bartolo Vittoria V Rizvi Ali A AA Montalto Giuseppe G Abate Nicola N
Cardiovascular diabetology 20140222
<h4>Background</h4>Liraglutide, a long-acting glucagon-like peptide-1 (GLP-1) analog, has several non- glycemic properties, but its effect on carotid intima-media thickness (IMT), a recognized marker of subclinical atherosclerosis, is still unknown.<h4>Methods</h4>A prospective study of 8 months duration in 64 patients with type-2 diabetes and no prior history of coronary artery disease evaluated whether adding liraglutide to metformin affects carotid IMT, measured by color doppler ultrasound.<h ...[more]
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Project description:BackgroundLiraglutide, a GLP-1 analogue, exerts several beneficial non-glycemic effects in patients with type-2 diabetes (T2DM), such as those on body weight, blood pressure, plasma lipids and inflammation markers. However, the effects of liraglutide on cardiovascular (CV) risk markers in subjects with the metabolic syndrome (MetS) are still largely unknown. We herein explored its effects on various cardio-metabolic risk markers of the MetS in subjects with T2DM.MethodsWe performed an 18-month prospective, real-world study. All subjects had T2DM and the MetS based on the AHA/NHLBI criteria. Subjects with a history of a major CV event were excluded. One hundred-twenty-one subjects (71 men and 50 women; mean age: 62 ± 9 years) with T2DM and the MetS, who were naïve to incretin-based therapies and treated with metformin only, were included. Liraglutide (1.2 mg/day) was added to metformin (1500-3000 mg/day) for the entire study. Fasting plasma samples for metabolic parameters were collected and carotid-intima media thickness (cIMT) was assessed by B-mode real-time ultrasound at baseline and every 6 months thereafter.ResultsThere was a significant reduction in waist circumference, body mass index, fasting glycemia, HbA1c, total- and LDL-cholesterol, triglycerides, and cIMT during the 18-month follow-up. Correlation analysis showed a significant association between changes in cIMT and triglycerides (r = 0.362; p < 0.0001). The MetS prevalence significantly reduced during the study, and the 26% of subjects no longer fulfilled the criteria for the MetS after 18 months.ConclusionsLiraglutide improves cardio-metabolic risk factors in subjects with the MetS in a real-world study. Trial Registration ClinicalTrials.gov: NCT01715428.
| S-EPMC5135832 | biostudies-literature
Project description:ObjectivePlasma total homocysteine (tHcy) has been positively associated with carotid intima-media thickness (IMT) in non-diabetic populations and in a few cross-sectional studies of diabetic patients. We investigated cross-sectional and prospective associations of a single measure of tHcy with common and internal carotid IMT over a 6-year period in type 1 diabetes.Research design and methodstHcy levels were measured once, in plasma obtained in 1997-1999 from patients (n = 599) in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the observational follow-up of the Diabetes Control and Complications Trial (DCCT). Common and internal carotid IMT were determined twice, in EDIC "Year 6" (1998-2000) and "Year 12" (2004-2006), using B-mode ultra-sonography.ResultsAfter adjustment, plasma tHcy [median (interquartile range): 6.2 (5.1, 7.5) μmol/L] was significantly correlated with age, diastolic blood pressure, renal dysfunction, and smoking (all p < 0.05). In an unadjusted model only, increasing quartiles of tHcy correlated with common and internal carotid IMT, again at both EDIC time-points (p < 0.01). However, multivariate logistic regression revealed no significant associations between increasing quartiles of tHcy and the 6-year change in common and internal carotid IMT (highest vs. lowest quintile) when adjusted for conventional risk factors.ConclusionsIn a type 1 diabetes cohort from the EDIC study, plasma tHcy measured in samples drawn in 1997-1999 was associated with measures of common and internal carotid IMT measured both one and seven years later, but not with IMT progression between the two time-points. The data do not support routine measurement of tHcy in people with Type 1 diabetes.
| S-EPMC4134979 | biostudies-literature
Project description:BackgroundIntima-media thickness of the walls of the common carotid artery and internal carotid artery may add to the Framingham risk score for predicting cardiovascular events.MethodsWe measured the mean intima-media thickness of the common carotid artery and the maximum intima-media thickness of the internal carotid artery in 2965 members of the Framingham Offspring Study cohort. Cardiovascular-disease outcomes were evaluated for an average follow-up of 7.2 years. Multivariable Cox proportional-hazards models were generated for intima-media thickness and risk factors. We evaluated the reclassification of cardiovascular disease on the basis of the 8-year Framingham risk score category (low, intermediate, or high) after adding intima-media thickness values.ResultsA total of 296 participants had a cardiovascular event. The risk factors of the Framingham risk score predicted these events, with a C statistic of 0.748 (95% confidence interval [CI], 0.719 to 0.776). The adjusted hazard ratio for cardiovascular disease with a 1-SD increase in the mean intima-media thickness of the common carotid artery was 1.13 (95% CI, 1.02 to 1.24), with a nonsignificant change in the C statistic of 0.003 (95% CI, 0.000 to 0.007); the corresponding hazard ratio for the maximum intima-media thickness of the internal carotid artery was 1.21 (95% CI, 1.13 to 1.29), with a modest increase in the C statistic of 0.009 (95% CI, 0.003 to 0.016). The net reclassification index increased significantly after addition of intima-media thickness of the internal carotid artery (7.6%, P<0.001) but not intima-media thickness of the common carotid artery (0.0%, P=0.99). With the presence of plaque, defined as intima-media thickness of the internal carotid artery of more than 1.5 mm, the net reclassification index was 7.3% (P=0.01), with an increase in the C statistic of 0.014 (95% CI, 0.003 to 0.025).ConclusionsThe maximum internal and mean common carotid-artery intima-media thicknesses both predict cardiovascular outcomes, but only the maximum intima-media thickness of (and presence of plaque in) the internal carotid artery significantly (albeit modestly) improves the classification of risk of cardiovascular disease in the Framingham Offspring Study cohort. (Funded by the National Heart, Lung, and Blood Institute.).
| S-EPMC3153949 | biostudies-literature
Project description:AimTo evaluate the relationship between periodontal diseases and subclinical atherosclerosis in a younger and lean South Asian population.MethodsWe conducted a cross-sectional study in 917 subjects (mean age 46 years and mean body mass index 21.1 kg/m2 ) from the Health Effects of Arsenic Longitudinal Study in Bangladesh. Multivariate linear regression models were used to assess the associations between multiple clinical measures of periodontal diseases and carotid intima-media thickness (IMT).ResultsMean attachment loss (AL) and percentage of sites with AL ≥ 4 mm (% AL ≥ 4) were associated with increased IMT. The IMT was 20.0-μm (95% CI: 2.2, 37.8) and 26.5-μm (95% CI: 8.9, 44.1) higher in subjects in the top quartile of mean AL (>3.72 mm) and % AL ≥ 4 (>58.4%), respectively, compared to those in the bottom quartile. In a subset of 366 subjects, mean AL was positively associated with plasma levels of matrix metalloproteinase-9 (p < 0.05) and soluble intercellular adhesion molecule-1 (p < 0.01).ConclusionsAttachment loss was associated with subclinical atherosclerosis in this young and lean Bangladeshi population. Future prospective studies are needed to confirm this association.
| S-EPMC5063685 | biostudies-literature
Project description:BackgroundThe anti-diabetic agent acarbose reduces postprandial glucose excursions. We have evaluated the effect of randomized treatment with acarbose on the progression of carotid intima-media thickness (IMT) in early diabetes.MethodsThe Early Diabetes Intervention Program was a randomized trial of acarbose versus placebo in 219 participants with early diabetes characterized by glucose values over 11.1 mmol/L 2 h after a 75 g oral glucose load and a mean HbA1c of 6.3%. IMT was measured at baseline and yearly. Follow-up was discontinued if participants progressed to the study glucose endpoints; IMT readings were available for a median of 2 years, with 72 subjects followed for 5 years.ResultsProgressive increases in IMT were seen in both treatment groups, but progression was reduced in participants randomized to acarbose (p = 0.047). In age, sex and smoking-adjusted analyses, IMT progression was associated with greater fasting and oral glucose tolerance test-excursion glucose, fasting insulin, cholesterol and glycated low-density lipoprotein concentrations. IMT progression was reduced with study-related changes in weight, insulin and non-esterified fatty acids; these features were more strongly associated with reduced IMT progression than acarbose treatment. Despite strong associations of baseline glycemia with IMT progression, study-related changes in glucose were not important determinants of IMT progression.ConclusionsAcarbose can delay progression of carotid intima-media thickness in early diabetes defined by an oral glucose tolerance test. Glucose, weight, insulin and lipids contributed to risk of progression but reductions in glycemia were not major determinants of reduced rate of IMT progression. Vascular benefits of acarbose may be independent of its glycemic effects.
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Project description:BACKGROUND:High parity is associated with greater cardiovascular disease (CVD) among mid-life and older women. Prospective studies of arterial change throughout pregnancy are needed to provide insight into potential mechanisms. This study assessed vascular adaptation across pregnancy in healthy first-time pregnant women. METHODS:The Maternal Vascular Adaptation to Healthy Pregnancy Study (Pittsburgh, PA, 2010-2015) assessed 37 primigravid women each trimester, 6-8 weeks after delivery and 1-5 years postpartum, with B-mode ultrasound imaging of common carotid artery (CCA) intima-media thickness (IMT) and inter-adventitial diameter (IAD) to assess associations with physical and cardiometabolic measures. RESULTS:Thirty-seven women (age 28.2?±?4.5 years, pre-pregnant BMI 24.4?±?3.2 kg/m2) experienced uncomplicated pregnancies. After adjustment for age and pre-pregnancy BMI, mean (SE) IAD (mm) increased each trimester, from 6.38 (0.08) in the 1st trimester to 6.92 (0.09) in the 3rd trimester, and then returned to 1st trimester levels postpartum (6.35 [0.07], P?<? 0.001). In contrast, mean (SE) CCA IMT (mm) increased from the 2nd trimester (i.e., 0.546 [0.01]) onward, and remained higher at an average of 2.7 years postpartum (0.581 [0.02], P?=?0.03). Weight partially explained changes in IAD. CONCLUSIONS:In uncomplicated first pregnancies, IAD increased and returned to 1st trimester levels postpartum. In contrast, CCA IMT remained increased 2 years postpartum. Maternal weight explained vascular changes better than did metabolic changes. Increased postpartum CCA IMT may persist and contribute to long-term CVD risk.
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Project description:Nitric oxide (NO) plays an important role in cardiovascular health by maintaining and regulating vascular tone and blood flow. Epigenetic regulation of NO synthase (NOS), the genes responsible for NO production, may affect cardiovascular disease, including the development of atherosclerosis in children.We measured percentage DNA methylation using bisulfite conversion and pyrosequencing assays on DNA from buccal cells provided by 377 participants of the Children's Health Study on whom carotid artery intima-media thickness (CIMT) measurements were also collected. We examined a total of 16 CpG loci located within NOS1, NOS2A, NOS3, ARG1, and ARG2 genes responsible for NO production. CIMT was measured using high-resolution B-mode carotid ultrasound. The association between percentage DNA methylation in ARG and NOS genes with CIMT was evaluated using linear regression adjusted for sex, ethnicity, body mass index, age at CIMT, town of residence, and experimental plate for pyrosequencing reactions. Differences in the association by ethnicity and ancestral group were also evaluated. For a 1% increase in average DNA methylation of NOS1, CIMT increased by 1.2 ?m (P=0.02). This association was greater in Hispanic children of Native American descent (?=2.3; P=0.004) than in non-Hispanic whites (?=0.3; P=0.71) or Hispanic whites (?=1.0; P=0.35).DNA methylation of NOS1 has a plausible role in atherogenesis through regulation of NO production, although ancestry may alter the magnitude of this association.
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Project description:Emerging evidence suggests associations between menopausal hot flashes and cardiovascular risk. However, whether hot flashes are associated with intima media thickness (IMT) or IMT changes over time is unknown. We hypothesized that reported hot flashes would be associated with greater IMT cross-sectionally and with greater IMT progression over 2 years.Participants were 432 women aged 45 to 58 years at baseline participating in the Study of Women's Health Across the Nation (SWAN) Heart, an ancillary study to the SWAN. Measures at the SWAN Heart baseline and follow-up visit 2 years later included a carotid artery ultrasound, reported hot flashes (past 2 weeks: none, 1-5 d, ?6 d), and a blood sample for measurement of estradiol.Women reporting hot flashes for 6 days or more in the prior 2 weeks had significantly higher IMT than did women without hot flashes at the baseline (mean [SE] difference, 0.02 [0.01] mm; P=0.03) and follow-up (mean [SE] difference, 0.02 [0.01] mm; P=0.04) visits, controlling for demographic factors and cardiovascular risk factors. Reporting hot flashes at both study visits was associated with higher follow-up IMT relative to reporting hot flashes at neither visit (mean [SE] difference, 0.03 [0.01] mm; P=0.03). Associations between hot flashes and IMT largely remained after adjusting for estradiol. An interaction between hot flashes and obesity status was observed (P=0.05) such that relations between hot flashes and IMT were observed principally among overweight/obese women. Hot flashes were not associated with IMT progression.These findings provide some indication that women reporting hot flashes for 6 days or more in the prior 2 weeks may have higher IMT than do women without hot flashes, particularly for women who are overweight or obese. Further work should determine whether hot flashes mark adverse underlying vascular changes.
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Project description:BACKGROUND:Cardiovascular disease in women often develops without conventional risk factors. Prenatal loss is a common pregnancy outcome that may result in physiological changes can increase the potential future risk of cardiovascular disease. Insufficient information exists regarding the impact of pregnancy loss on early markers of cardiovascular disease risk. METHODS AND RESULTS:Cross-sectional analysis of 1767 disease-free women from the MTC (Mexican Teachers' Cohort) who had been pregnant was used to evaluate the relationship between pregnancy loss and carotid intima-media thickness (IMT). Participants responded to a questionnaire regarding their reproductive history, risk factors, and medical conditions. We defined pregnancy loss as history of miscarriage and/or stillbirth. Trained neurologists measured IMT using ultrasound. We log-transformed IMT and defined subclinical carotid atherosclerosis (SCA) as IMT ?0.8 mm and/or plaque. We used multivariable linear and logistic regression models to assess the relation of pregnancy loss, IMT, and SCA. The mean age of participants was 49.8±5.1 years. The prevalence of pregnancy loss was 22%, and we observed SCA in 23% of participants. Comparing participants who reported a pregnancy loss and those who did not, the multivariable-adjusted odds ratio for SCA was 1.52 (95% confidence interval, 1.12-2.06). Women who experienced a stillbirth had 2.32 higher odds (95% confidence interval, 1.03-5.21) of SCA than those who did not. Mean IMT appeared to be higher in women who reported a pregnancy loss relative to those who did not; nevertheless, this was not statistically significant. CONCLUSIONS:Pregnancy loss could be linked to cardiovascular disease later in life. The key findings of our study await confirmation and further investigation of the potential underlying mechanisms for this association is required.
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Project description:Atherosclerotic changes can be measured as changes in common carotid intima media thickness (CIMT). It is hypothesised that repeated infection-associated inflammatory responses in childhood contribute to the atherosclerotic process. We set out to determine whether the frequency of infectious diseases in childhood is associated with CIMT in adolescence. The study is part of the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) population-based birth cohort. At age 16 years, common CIMT was measured. We collected general practitioner (GP) diagnosed infections and prescribed antibiotics. Parent-reported infections were retrieved from annual questionnaires. Linear regression analysis assessed the association between number of infections during the first 4 years of life and common CIMT. Common CIMT measurement, GP and questionnaire data were available for 221 participants. No association was observed between the infection measures and CIMT. In a subgroup analysis, significant positive associations with CIMT were observed in participants with low parental education for 2-3 or ⩾7 GP diagnosed infections (+26.4 µm, 95% CI 0.4-52.4 and +26.8 µm, 95% CI 3.6-49.9, respectively) and ⩾3 antibiotic prescriptions (+35.5 µm, 95%CI 15.8-55.3). Overall, early childhood infections were not associated with common CIMT in adolescence. However, a higher number of childhood infections might contribute to the inflammatory process of atherosclerosis in subgroups with low education, this needs to be confirmed in future studies.
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