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Effect of the GSTM1 gene deletion on glycemic variability, sympatho-vagal balance and arterial stiffness in patients with metabolic syndrome, but without diabetes.
Iorio, A, Ylli, D, Polimanti, R, Picconi, F, Maggio, P, Francomano, D, Aversa, A, Manfellotto, D, Fuciarelli, M, Frontoni, S
Diabetes research and clinical practice. 2018;:158-168
Abstract
AIMS: An increased rate of cerebrovascular complications in patients with metabolic syndrome (MetS) has been reported. Previous studies demonstrated an association between glycemic variability (GV) and cerebrovascular reactivity (CRV) in MetS, thus suggesting a putative role of GV on cerebrovascular events. Although the pathophysiological mechanism linking GV to damage is still to be elucidated, evidence suggests oxidative stress plays a crucial role. Since functional variants in glutathione S-transferases (GST) genes modulate the cellular detoxification processes, the aim of this study was to elucidate the involvement of GSTs in MetS and investigating the correlation with GV, arterial stiffness, and sympatho-vagal (SV) balance. METHODS A hundred metabolic syndrome patients without diabetes underwent GST gene polymorphism analysis and a sub-sample 36 patients were randomly selected to investigate the correlation between GST gene polymorphisms and GV, and sympatho-vagal (SV) balance and arterial stiffness. RESULTS GSTM1 showed a significant association with several GV, arterial stiffness, and SV balance indexes. In particular, the GSTM1 deletion positively correlates with lower values of these indexes when compared to the presence of the gene. CONCLUSIONS Therefore, we suggested a global influence of GSTM1 deletion on the GV, arterial stiffness, and SV balance pathways in MetS patients, probably also interacting with AMP-activated protein kinase (AMPK) regulation. Our novel findings indicate GSTM1 could be a risk locus in MetS development and shed light novel scenarios on the role of glucose fluctuations in neurological impairments.
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Effect of Lactotripeptides (Isoleucine-Proline-Proline/Valine-Proline-Proline) on Blood Pressure and Arterial Stiffness Changes in Subjects with Suboptimal Blood Pressure Control and Metabolic Syndrome: A Double-Blind, Randomized, Crossover Clinical Trial.
Cicero, AF, Colletti, A, Rosticci, M, Cagnati, M, Urso, R, Giovannini, M, Borghi, C, D'Addato, S
Metabolic syndrome and related disorders. 2016;(3):161-6
Abstract
BACKGROUND Lactotripeptides (LTPs) have a mild antihypertensive effect in hypertensive subjects. The main aim of our clinical trial was to test if LTPs could have some influence on blood pressure (BP) and related hemodynamic parameters in a sample of outpatients affected by metabolic syndrome. METHODS A randomized, double-blind, placebo-controlled, crossover clinical trial was conducted in a group of 40 nonsmoking volunteers with metabolic syndrome. The treatment periods were 4 weeks long and were separated by a 4-week washout period. The dietary supplementation was made by daily administration of LTPs from casein, 10.2 mg/day, and compared with placebo. RESULTS During the LTP treatment, patients experienced a significant mean decrease in systolic BP (SBP; -3.4 ± 4.4 mmHg, P = 0.041), diastolic BP (DBP; -3.1 ± 3.2 mmHg, P = 0.049), and pulse wave velocity (PWV; -0.7 ± 0.3 m/sec, P = 0.001). After LTP treatment, delta SBP, DBP, and PP were all significantly improved (P < 0.01 for all) compared with placebo. PWV also improved significantly after LTP treatment with respect to the end of the treatment with placebo (-0.8 ± 0.4 vs. -0.1 ± 0.3 m/sec, P = 0.009). The square root of the ratio of peak:baseline pulse volume during hyperemia (√V2/V1) improved after LTP treatment only (1.2 ± 0.4 vs. 1.4 ± 0.5, P = 0.04). Through the evaluation of the hemodynamic parameters that were measured by the 24-hr ambulatory monitoring, we observed that SBP, MBP, and the percentage of time with SBP over the normal were significantly reduced only after the LTP treatment (P < 0.05). These parameters were also significantly improved when compared with the ones measured after the placebo treatment (P < 0.05). CONCLUSION In our trial, during LTP treatment, patients affected by metabolic syndrome experienced a mild but significant improvement in office and 24-hr BP, PWV, and endothelial function compared with placebo treatment.
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Early vascular aging in young and middle-aged ischemic stroke patients: the Norwegian Stroke in the Young Study.
Saeed, S, Waje-Andreassen, U, Fromm, A, Øygarden, H, Kokorina, MV, Naess, H, Gerdts, E
PloS one. 2014;(11):e112814
Abstract
BACKGROUND Ischemic stroke survivors have high risk of cardiovascular morbidity and mortality even at young age, suggesting that early arterial aging is common among such patients. METHODS We measured aortic stiffness by carotid-femoral pulse wave velocity (PWV) in 205 patients (69% men) aged 15-60 years with acute ischemic stroke in the prospective Norwegian Stroke in the Young Study. High for age carotid-femoral PWV was identified in the reference normogram. RESULTS Patients were on average 49 ± 10 years old, 34% had a history of hypertension and 37% had metabolic syndrome (MetS). In the total study population, higher PWV was associated with history of hypertension (β = 0.18), higher age (β = 0.34), systolic blood pressure (BP) (β = 0.28) and serum creatinine (β = 0.18) and lower high-density lipoprotein (HDL) cholesterol (β = -0.10, all p < 0.01) in multivariate linear regression analysis (multiple R2 = 0.42, p < 0.001). High for age PWV was found in 18% of patients. In univariate analyses, known hypertension was associated with a 6-fold, MetS with a 4-fold and presence of carotid plaque with a 3.7-fold higher risk for high for age PWV (all p < 0.01). In multiple logistic regression analysis higher systolic BP (odds ratio [OR] 1.04; 95% confidence interval [CI] 1.02-1.06; p < 0.01), history of hypertension (OR 3.59; 95% CI 1.52-8.51; p < 0.01), low HDL cholesterol (OR 3.03; 95% CI 1.00-9.09; p = 0.05) and higher serum creatinine (OR 1.04; 95% CI 1.01-1.06; p < 0.01) were associated with high for age PWV. CONCLUSIONS Higher PWV is common in younger and middle-aged ischemic stroke patients and associated with a clustering of classical cardiovascular risk factors. ClinicalTrials.gov NCT01597453.
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Central adiposity and protein intake are associated with arterial stiffness in overweight children.
Arnberg, K, Larnkjær, A, Michaelsen, KF, Mølgaard, C
The Journal of nutrition. 2012;(5):878-85
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Abstract
Being overweight is associated with vascular abnormalities, which are important in the development of atherosclerosis. However, little is known about dietary and lifestyle determinants of vascular function in overweight children. In adults, dietary protein and milk intake are associated with reduced blood pressure and reduced risk of metabolic syndrome. This study examined the associations between dietary protein, milk intake, physical activity, and adiposity on arterial stiffness in overweight children. In a cross-sectional study, overweight children with habitual milk intakes ≤ 250 mL/d were examined by DXA scans, pedometer counts, anthropometry, and metabolic variables. Dietary intake was registered for 4 d. The outcomes were arterial stiffness measured by pulse wave velocity (PWV) (n = 182) and augmentation index (Aix) (n = 183). The PWV (mean ± SD) was 4.78 ± 0.72 m/s and the Aix was -0.77 ± 9.44%. In multivariate models, the android fat:gynoid fat and android fat:body fat ratios were positively associated with PWV (β = 1.49 and β = 10.3, both P < 0.05) and Aix (β = 28.3, P < 0.01 and β = 153, P < 0.05), whereas the gynoid fat:body fat ratio was negatively associated with the Aix (β = -134; P < 0.001). Protein intake (percentage energy) was positively associated with PWV (β = 0.05; P < 0.01). Milk intake (L/d) tended to be negatively associated with PWV (β = -0.64; P = 0.05). Pedometer counts were negatively associated with the Aix; however, the association became nonsignificant after controlling for HOMA, which was positively associated with the Aix (β = 0.95; P < 0.01). In conclusion, central adiposity and protein intake are associated with increased arterial stiffness measured as PWV in overweight children independent of blood pressure and heart rate. The effect of protein intake may be caused by meat, because the milk intake was low.