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The Effects of Vitamin D Supplementation on Metabolic and Oxidative Stress Markers in Patients With Type 2 Diabetes: A 6-Month Follow Up Randomized Controlled Study.
Cojic, M, Kocic, R, Klisic, A, Kocic, G
Frontiers in endocrinology. 2021;:610893
Abstract
Vitamin D deficiency could play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) as it may alter several crucial processes in the development of diabetes and its complications, such as pancreatic insulin secretion, peripheral insulin resistance, persistence of systemic "sterile" inflammation and immune activation. Vitamin D may also have an antioxidant effect through the inhibition of free radicals generation. The reported study was designed with eligible consecutively recruited patients with T2DM on standard metformin therapy (n=130), randomized in 1:1 ratio, considered to have undergone Vitamin D supplementation according to the guidelines proposed by the Endocrine Society, or to have continued with metformin only. The potential benefit was monitored through the influence on glycemia level, glycated haemoglobin (HbA1c), insulin resistance index (calculated as homeostatic model assessment; HOMA-IR), Castelli Risk Index I and Tryglicerides/Thiobarbituric acid-reactive substances (TG/TBARS) Index in a 6-month follow up period. Our study indicates that oral daily doses of vitamin D improve HbA1c levels over the 3-month and 6-month period, followed by a significant decrease in advanced oxidation protein products levels over the 3-month period when higher vitamin D doses are given. The effect of vitamin D on HOMA-IR index, malondialdehyde levels and TG/TBARS index was not statistically significant. Further investigation should consider defining the doses of vitamin D in patients with T2DM which may attenuate the oxidative stress risk, the risk of metabolic syndrome and the risk of related cardiovascular events.
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Policaptil Gel Retard in adult subjects with the metabolic syndrome: Efficacy, safety, and tolerability compared to metformin.
Guarino, G, Della Corte, T, Strollo, F, Gentile, S, ,
Diabetes & metabolic syndrome. 2021;(3):901-907
Abstract
BACKGROUND Policaptil Gel Retard® (PGR), is a new macromolecule complex based on polysaccharides slowing the rate of carbohydrate and fat absorption. It proved to significantly reduce body weight, acanthosis nigricans expression, HbA1c levels, and glucose metabolism abnormalities in obese, hyper-insulinemic adolescents. No such data are available for adults. AIM: to compare the effects of PGR vs. metformin in adult subjects with the Metabolic Syndrome (MS) and T2DM on a Low Glycemic Index diet. SUBJECTS AND METHODS This spontaneous clinical, longitudinal, single-blind, randomized study based on a per-protocol analysis enrolled 100 outpatients with MS and T2DM consecutively referring to our clinic for three months, and randomly assigned to either the active treatment (Group A:, 6 tablets/day) or the comparator (Group B: Metformin tablets, 1500-2000 mg/day in two divided doses during the two main meals, to minimize side effects) to be taken 30 min before each main meal in equally divided doses. Serum lipid profile, anthropometry, HOMA-IR index, and tolerability parameters were evaluated before and after a 6-month follow-up period. RESULTS all parameters improved at a similar rate in both groups but for the lipid profile, which got even better in Group A. Group A also experienced less prominent gastrointestinal side effects than its counterpart. CONCLUSION For the first time, we showed the non-inferiority of PGR compared to metformin in obese adult subjects with the MS and T2DM as for glycemic control and a clear-cut superiority of PGR in terms of both serum lipid-lowering capacity and tolerability.
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Favorable Changes in Biomarkers of Potential Harm to Reduce the Adverse Health Effects of Smoking in Smokers Switching to the Menthol Tobacco Heating System 2.2 for 3 Months (Part 2).
Haziza, C, de La Bourdonnaye, G, Donelli, A, Skiada, D, Poux, V, Weitkunat, R, Baker, G, Picavet, P, Lüdicke, F
Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco. 2020;(4):549-559
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INTRODUCTION Tobacco Heating System (THS) 2.2, a candidate modified-risk tobacco product, aims at offering an alternative to cigarettes for smokers while substantially reducing the exposure to harmful and potentially harmful constituents found in cigarette smoke. METHODS One hundred and sixty healthy adult US smokers participated in this randomized, three-arm parallel group, controlled clinical study. Subjects were randomized in a 2:1:1 ratio to menthol Tobacco Heating System 2.2 (mTHS), menthol cigarette, or smoking abstinence for 5 days in confinement and 86 subsequent ambulatory days. Endpoints included biomarkers of exposure to harmful and potentially harmful constituents (reported in our co-publication, Part 1) and biomarkers of potential harm (BOPH). RESULTS Compliance (protocol and allocated product exposure) was 51% and 18% in the mTHS and smoking abstinence arms, respectively, on day 90. Nonetheless, favorable changes in BOPHs of lipid metabolism (total cholesterol and high- and low-density cholesterol), endothelial dysfunction (soluble intercellular adhesion molecule-1), oxidative stress (8-epi-prostaglandin F2α), and cardiovascular risk factors (eg, high-sensitivity C-reactive protein) were observed in the mTHS group. Favorable effects in other BOPHs, including ones related to platelet activation (11-dehydrothromboxane B2) and metabolic syndrome (glucose), were more pronounced in normal weight subjects. CONCLUSIONS The results suggest that the reduced exposure demonstrated when switching to mTHS is associated with overall improvements in BOPHs, which are indicative of pathomechanistic pathways underlying the development of smoking-related diseases, with some stronger effects in normal weight subjects. IMPLICATIONS Switching to mTHS was associated with favorable changes for some BOPHs indicative of biological pathway alterations (eg, oxidative stress and endothelial dysfunction). The results suggest that switching to mTHS has the potential to reduce the adverse health effects of smoking and ultimately the risk of smoking-related diseases. Switching to mTHS for 90 days led to reductions in a number of biomarkers of exposure in smokers, relative to those who continued smoking cigarettes, which were close to those observed when stopping smoking (reported in our co-publication, Part 1). Initial findings suggest reduced levels of 8-epi-prostaglandin F2α and intercellular adhesion molecule 1, when switching to mTHS for 90 days. These changes are comparable to what is observed upon smoking cessation. In normal weight subjects, additional favorable changes were seen in 11-dehydrothromboxane B2, fibrinogen, homocysteine, hs-CRP, percentage of predicted forced expiratory volume in 1 second, systolic blood pressure, diastolic blood pressure, glucose, high-density lipoprotein, apolipoprotein A1, and triglycerides. TRIAL REGISTRATION NCT01989156.
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Effects of Montmorency Tart Cherry Juice Consumption on Cardiometabolic Biomarkers in Adults with Metabolic Syndrome: A Randomized Controlled Pilot Trial.
Johnson, SA, Navaei, N, Pourafshar, S, Jaime, SJ, Akhavan, NS, Alvarez-Alvarado, S, Proaño, GV, Litwin, NS, Clark, EA, Foley, EM, et al
Journal of medicinal food. 2020;(12):1238-1247
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Greater than one-third of adults in the United States have metabolic syndrome (MetS), a cluster of risk factors highly associated with the development of cardiovascular diseases. Premature vascular dysfunction in MetS may lead to accelerated age-related atherogenesis and arterial stiffening, thereby increasing cardiovascular risk. Montmorency tart cherries (Prunus cerasus L.) are rich in bioactive compounds, such as anthocyanins, known to exert cardiovascular protective effects. Previous research suggests that tart cherry juice consumption may improve cardiovascular health. The objective of this study was to evaluate the effects of daily consumption of tart cherry juice on hemodynamics, arterial stiffness, and blood biomarkers of cardiovascular and metabolic health in men and women with MetS. In a randomized, single-blind, placebo-controlled, parallel-arm pilot clinical trial, 19 men and women 20 to 60 years of age with MetS consumed 240 mL of tart cherry juice (Tart Cherry; n = 5 males, 4 females) or an isocaloric placebo-control drink (Control; n = 5 males, 5 females) twice daily for 12 weeks. Arterial stiffness (pulse wave velocity), brachial and aortic blood pressures, wave reflection (augmentation index), and blood biomarkers of cardiovascular and metabolic health were assessed at baseline and 6 and 12 weeks. Oxidized low-density lipoprotein and soluble vascular cell adhesion molecule-1 were significantly lower (P = .047 and P = .036, respectively) in Tart Cherry than Control at 12 weeks, but were not significantly lower than baseline values. There was a trend for total cholesterol to be lower (P = .08) in Tart Cherry than Control at 12 weeks. No significant changes were observed in hemodynamics, arterial stiffness, or other blood biomarkers assessed. These results suggest that daily tart cherry consumption may attenuate processes involved in accelerated atherogenesis without affecting hemodynamics or arterial stiffness parameters in this population. The pilot nature of this study warrants interpreting these findings with caution, and future clinical trials with a larger sample size are needed to confirm these findings.
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The Effect of Oligopin Supplementation on Hormonal and Metabolic Profiles in the Polycystic Ovary Syndrome: A Randomized Controlled Trial.
Qorbani, M, Sanginabadi, M, Mohajeri-Tehrani, MR, Karimi, S, Gerami, H, Mahdavi-Gorabi, A, Shirzad, N, Samadi, M, Baygi, F, Hosseini, S, et al
Frontiers in endocrinology. 2020;:590392
Abstract
BACKGROUND A double blind clinical trial was performed to evaluate whether the polycystic ovary syndrome (PCOS)-specific serum markers and metabolic parameters would change in the women with PCOS during the three-month administration of oligopin. METHODS In this double-blind multicenter trial, we randomly assigned 80 PCOS women, based on a 1:1 ratio, to receive oligopin (n= 40) or maltodextrin as placebo (n = 40) for up to 3 months. As PCOS-specific outcomes, we investigated the changes in testosterone, sex hormone binding globulin (SHBG), free androgen index (FAI), dehydroepiandrosterone (DHEA), follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Secondary end points were metabolic (fasting glycaemia, hemoglobin A1c (HbA1c), lipids, insulin resistance (HOMA-IR)), anthropometrics parameters and blood pressure from the baseline to the end of treatment. We investigated serum transaminase, alkaline phosphatase (ALP), creatinine (Cr) and blood urea nitrogen (BUN) levels as hepatic and kidney outcomes, respectively. RESULTS The first participant was enrolled on April 18, 2018, and the last study visit took place on May 14, 2019. PCOS-specific serum parameters did not change during the three-month administration of oligopin (p > 0.05), except for a small increase in the FSH levels (p=0.03). Oligopin neither changed the metabolic profile nor the anthropometric parameters or blood pressure. ALP levels was significantly increased in placebo group, as compared with oligopin (p=0.01). CONCLUSION Oligopin supplementation does not seem to be exerting a beneficial effect on both hormonal and metabolic parameters in the women with PCOS. CLINICAL TRIAL REGISTRATION www.irct.ir, identifier IRCT20140406017139N3.
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The Effect of Perimenopausal Transdermal Estradiol and Micronized Progesterone on Markers of Risk for Arterial Disease.
Gordon, JL, Rubinow, DR, Watkins, L, Hinderliter, AL, Caughey, MC, Girdler, SS
The Journal of clinical endocrinology and metabolism. 2020;(5):e2050-60
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BACKGROUND The arterial effects of hormone therapy remain controversial. This study tested the effects of transdermal estradiol plus intermittent micronized progesterone (TE + IMP) in healthy perimenopausal and early postmenopausal women on several mechanisms involved in the pathophysiology of arterial disease. METHODS Healthy perimenopausal and early postmenopausal women, ages 45 to 60 years, were enrolled in this randomized, double-blind, placebo-controlled trial. Women were randomized to receive TE (0.1 mg/day) + IMP (200 mg/day for 12 days) or identical placebo patches and pills for 12 months. Outcomes included: change in stress reactivity composite z-score (combining inflammatory, cortisol, and hemodynamic responses to a standardized psychological laboratory stressor); flow-mediated dilation (FMD) of the brachial artery (an index of vascular endothelial function); baroreflex sensitivity; and metabolic risk (presence of the metabolic syndrome or insulin resistance), all assessed at baseline and at months 6 and 12. RESULTS Of 172 women enrolled, those assigned to TE + IMP tended to have higher resting baroreflex sensitivity than those assigned to placebo across the 6- and 12-month visits. Although treatment groups did not differ in terms of the other prespecified outcomes, a significant treatment-by-age interaction was found for FMD and stress reactivity such that an age-related decrease in FMD and increase in stress reactivity were seen among women assigned to placebo but not those assigned to TE + IMP. Women on TE + IMP also had lower resting diastolic blood pressure, lower levels of low-density lipoprotein cholesterol, and higher baroreflex sensitivity during stress testing. CONCLUSIONS TE + IMP tended to improve cardiac autonomic control and prevented age-related changes in stress reactivity and endothelial function among healthy perimenopausal and early postmenopausal women.
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Blueberries improve biomarkers of cardiometabolic function in participants with metabolic syndrome-results from a 6-month, double-blind, randomized controlled trial.
Curtis, PJ, van der Velpen, V, Berends, L, Jennings, A, Feelisch, M, Umpleby, AM, Evans, M, Fernandez, BO, Meiss, MS, Minnion, M, et al
The American journal of clinical nutrition. 2019;(6):1535-1545
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BACKGROUND Anthocyanin-rich blueberry intake is associated with reduced type 2 diabetes and cardiovascular disease (CVD) risk in prospective studies, although long-term randomized controlled trials (RCTs) have not been conducted in at-risk populations. OBJECTIVE In the longest-duration RCT to date, we examined the effect of 6-mo blueberry intake on insulin resistance and cardiometabolic function in metabolic syndrome. METHODS A double-blind, parallel RCT (n = 115; age 63 ± 7 y; 68% male; body mass index 31.2 ± 3.0 kg/m2) was conducted, which fed 2 dietarily achievable blueberry intakes [equivalent to 1/2 and 1 cup/d (75/150 g)] compared with matched placebo. Insulin resistance was assessed via the homeostasis model assessment of insulin resistance (primary endpoint) and confirmed by [6-6-2H2]-glucose-labeled, 2-step hyperinsulinemic clamp (n = 20). Clinically relevant cardiometabolic endpoints [including flow-mediated dilatation, augmentation index, lipoprotein status (by nuclear magnetic resonance spectroscopy), and nitric oxide (NO)-related metabolite assay] and anthocyanin metabolism were assessed. RESULTS A daily intake of 1 cup of blueberries improved endothelial function (flow-mediated dilatation: +1.45%; 95% CI: 0.83%, 2.1%; P = 0.003), systemic arterial stiffness (augmentation index: -2.24%; 95% CI: -3.97%, -0.61%; P = 0.04) and attenuated cyclic guanosine monophosphate concentrations. In statin nonusers (n = 71), elevated high-density lipoprotein cholesterol (+0.08 mmol/L; P = 0.03), high-density lipoprotein particle density (+0.48n, ×10-6; P = 0.002) and apolipoprotein A-I (+0.05 g/L; P = 0.01) concentrations were observed following the 1-cup/d intervention. Treatment compliance was 94.1% (wrapper returns) and total concentrations of anthocyanin-derived phenolic acid metabolites significantly increased, dose-dependently, in serum and 24-h urine (P < 0.01 and P < 0.001, respectively). Insulin resistance, pulse wave velocity, blood pressure, NO, and overall plasma thiol status were unaffected. Likewise, a half cup per day had no effect on any biomarkers. CONCLUSIONS Despite insulin resistance remaining unchanged we show, to our knowledge, the first sustained improvements in vascular function, lipid status, and underlying NO bioactivity following 1 cup blueberries/d. With effect sizes predictive of 12-15% reductions in CVD risk, blueberries should be included in dietary strategies to reduce individual and population CVD risk. This study was registered at clinicaltrials.gov as NCT02035592.
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Relations of GlycA and lipoprotein particle subspecies with cardiovascular events and mortality: A post hoc analysis of the AIM-HIGH trial.
Otvos, JD, Guyton, JR, Connelly, MA, Akapame, S, Bittner, V, Kopecky, SL, Lacy, M, Marcovina, SM, Muhlestein, JB, Boden, WE
Journal of clinical lipidology. 2018;(2):348-355.e2
Abstract
BACKGROUND The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes trial showed no incremental benefit of extended-release niacin (ERN) therapy added to simvastatin in subjects with cardiovascular disease (CVD). OBJECTIVES To examine the effects of ERN treatment on lipoprotein particles and GlycA, a new marker of systemic inflammation, and their relations with incident CVD events including mortality. METHODS GlycA and very low-density lipoprotein, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) particle subclasses were quantified by nuclear magnetic resonance spectroscopy using available stored baseline (n = 2754) and 1-year in-trial (n = 2581) samples. Associations with CVD events and all-cause mortality were assessed using multivariable Cox proportional hazards regression adjusted for age, sex, diabetes, treatment assignment, and lipoproteins. RESULTS Compared to placebo, ERN treatment lowered very low-density lipoprotein and LDL and increased HDL particle concentrations, increased LDL and HDL particle sizes (all P < .0001), but did not affect GlycA. Baseline and in-trial GlycA levels were associated with increased risk of CVD events: hazard ratio (HR) per SD increment, 1.17 (95% confidence interval [CI], 1.06-1.28) and 1.13 (1.02-1.26), respectively. However, none of the lipoprotein particle classes or subclasses was associated with incident CVD. By contrast, all-cause mortality was significantly associated with both GlycA (baseline HR: 1.46 [1.22-1.75]; in-trial HR: 1.41 [1.24-1.60]) and low levels of small HDL particles (baseline HR: 0.69 [0.56-0.86]; in-trial HR: 0.69 [0.56-0.86]). CONCLUSIONS This Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes trial post hoc substudy indicates that inflammation, as indexed by GlycA, is unaffected by ERN treatment but is significantly associated with the residual risk of CVD and death in patients treated to low levels of LDL cholesterol.
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Vitamin D, parathyroid hormone and metabolic syndrome - the PORMETS study.
Raposo, L, Martins, S, Ferreira, D, Guimarães, JT, Santos, AC
BMC endocrine disorders. 2017;(1):71
Abstract
BACKGROUND Vitamin D (VitD) and parathyroid hormone (PTH) play important roles in calcium metabolism and skeletal homeostasis. Estimates of the VitD status in several European countries show large variations between them. In addition, no national population-based estimate has been published. VitD and PTH may also play important roles in cardiovascular risk, which has been suggested to be associated with metabolic syndrome (MetS) and is very prevalent in Portugal. The goal of our study was to evaluate the prevalence of hypovitaminosis D and its determinants as well as PTH serum level determinants and associations of the 25-hydroxyvitamin D and PTH serum levels with MetS and its individual components in a sample of the Portuguese mainland population. METHODS PORMETS is a national cross-sectional study that includes a total sample of 4095 adults. A subsample, including 500 participants, was randomly selected for the present study. A structured questionnaire was administered to collect information on personal medical histories and socio-demographic and behavioral characteristics. Blood pressure and anthropometrics measurements were performed. Fasting venous samples were collected and PTH and 25-hydroxyvitamin D were measured. VitD adequacy was classified according to the Institute of Medicine, and MetS was classified according to the Joint Interim Statement recommendations. Multiple linear regression and unconditional logistic regression models were used to estimate the associations between the levels of PTH and 25-hydroxyvitamin D and with MetS and its individual components. RESULTS The prevalence of VitD deficiency was 37.7%, and MetS was present in 191 participants (38.4%). The serum PTH levels showed a positive association (OR: 1.014; 95%CI: 1.002, 1.026) with the waist circumference component of MetS. The serum 25-hydroxyvitamin D levels were negatively associated with MetS (OR: 0.957; 95%CI: 0.922, 0.993) as well as with its blood pressure (OR: 0.949; 95%CI: 0.912, 0.987) and triglycerides (OR: 0.930; 95%CI: 0.892, 0.969) components. CONCLUSION This study showed a high national prevalence of hypovitaminosis D. The PTH levels showed a significant positive association with the WC component of MetS, and the VitD levels were negatively associated with the BP and triglycerides components as well as with the MetS.
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Increased static and decreased capacity oxidation-reduction potentials in plasma are predictive of metabolic syndrome.
Bobe, G, Cobb, TJ, Leonard, SW, Aponso, S, Bahro, CB, Koley, D, Mah, E, Bruno, RS, Traber, MG
Redox biology. 2017;:121-128
Abstract
Electric conductivity in plasma is the balance between oxidized and reduced molecules (static Oxidation-Reduction Potential, sORP) and the amount of readily oxidizable molecules (capacity ORP, cORP). Adults with metabolic syndrome (MetS) have increased inflammation, dyslipidemia and oxidative stress; therefore, participants with MetS were hypothesized to have higher plasma sORP and lower cORP than those measures in healthy adults. Heparin-anticoagulated plasma from healthy and age- and gender-matched individuals with MetS (BMI: 22.6±0.7 vs. 37.7±3.0kg/m2, respectively) was collected in the fasting state at 0, 24, 48, and 72h during each of four separate interventions in a clinical trial. At baseline, plasma sORP was 12.4% higher (P=0.007), while cORP values were less than half (41.1%, P=0.001) in those with MetS compared with healthy participants. An sORP >140mV detected MetS with 90% sensitivity and 80% specificity, while a cORP <0.50μC detected MetS with 80% sensitivity and 100% specificity. sORP and cORP values in participants with MetS compared with healthy adults were linked to differences in waist circumference and BMI; in plasma markers of dyslipidemia (triglycerides, HDL-cholesterol, and oxidized LDL-cholesterol) and inflammation (C-reactive protein, IL-10); as well as with urinary markers of lipid peroxidation (e.g., 2,3-dinor-5,6-dihydro-8-iso-PGF2α; 2,3-dinor-8-iso-PGF2α). Higher sORP values are a robust indicator of metabolic stress, while lower cORP values act as an indicator of decreased metabolic resilience.