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Pathophysiology of Gastroparesis Syndromes Includes Anatomic and Physiologic Abnormalities.
Abell, TL, Kedar, A, Stocker, A, Beatty, K, McElmurray, L, Hughes, M, Rashed, H, Kennedy, W, Wendelschafer-Crabb, G, Yang, X, et al
Digestive diseases and sciences. 2021;(4):1127-1141
Abstract
BACKGROUND Factors underlying gastroparesis are not well defined. AIMS We hypothesized that multiple systems may be involved in patients with gastroparesis symptoms and performed a comparative physiologic study. METHODS We studied 43 consecutive eligible patients with gastroparetic symptoms categorized by GI symptoms, metabolic status, illness quantification, and gastric physiology. Patients were evaluated by two methods in each of five core areas: inflammatory, autonomic, enteric, electrophysiologic, and hormonal with abnormalities examined by correlations. RESULTS Patients had similar GI symptoms regardless of baseline gastric emptying or diabetic/idiopathic status, and all patients demonstrated abnormalities in each of the 5 areas studied. Nearly all patients presented with elevated markers of serum TNFα (88%) and serum IL-6 (91%); elevated cutaneous electrogastrogram frequency (95%); and interstitial cells of Cajal count abnormalities (inner: 97%, outer: 100%). Measures of inflammation correlated with a number of autonomic, enteric anatomy, electrophysiologic and hormonal abnormalities. CONCLUSIONS We conclude that patients with the symptoms of gastroparesis have multiple abnormalities, when studied by traditional, as well as newer, diagnostic assessments. Inflammation appears to be a fundamental abnormality that affects other organ systems in symptomatic patients. Future work on gastroparetic syndromes and their treatment may benefit from a focus on the diffuse nature of their illness, diverse pathophysiologic mechanisms involved, especially the possible causes of underlying inflammation and disordered hormonal status. TRAIL REGISTRY This study is registered with Clinicaltrials.gov under study # NCT03178370 https://clinicaltrials.gov/ct2/show/NCT03178370 .
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Effect of atorvastatin on lipogenic, inflammatory and thrombogenic markers in women with the metabolic syndrome.
Velarde, GP, Choudhary, N, Bravo-Jaimes, K, Smotherman, C, Sherazi, S, Kraemer, DF
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(2):634-640
Abstract
BACKGROUND AND AIM Specific drug therapy to target the underlying proinflammatory and prothrombotic state in patients with metabolic syndrome (MS) is lacking. We sought to study the effect of high-intensity atorvastatin on markers of lipogenesis, inflammation and thrombogenesis, in women with MS in the absence of cardiovascular disease or diabetes. METHODS AND RESULTS This randomized double-blinded controlled trial included 88 women with MS (according to National Cholesterol Education Panel Adult Treatment Panel III criteria) and low atherosclerotic cardiovascular risk. Participants were randomized to receive atorvastatin 80 mg or matching placebo. Thrombogenic, lipogenic and inflammatory markers were collected at the time of enrollment, after a 6-week dietary run-in phase (time of randomization), and at 6- and 12-weeks after randomization. At 6 weeks post-randomization, there was significant reduction in total cholesterol, low density lipoprotein cholesterol, triglycerides, apolipoprotein-B (Apo-B) and Apo-B/Apo-A1 ratio in the atorvastatin arm compared to placebo. This difference persisted at 12-weeks post randomization. There was no significant difference in fasting blood glucose, high-density lipoprotein cholesterol, high sensitivity C-reactive protein, serum leptin, Apo-A1, intercellular adhesion molecule 1 and platelet activity. A significant increase in vascular adhesion molecule 1 at 6 and 12 weeks was seen within the atorvastatin arm. No difference was observed in blood pressure and waist circumference. CONCLUSIONS In conclusion, high-intensity atorvastatin has an early and significant impact on lipoproteins and apolipoproteins but did not lower inflammatory, thrombogenic or biomarkers of platelet activity and aggregation in women with MS. The use of statins for primary prevention in these patients should be further explored.
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Sex-Specific Regulation of Inflammation and Metabolic Syndrome in Obesity.
Ter Horst, R, van den Munckhof, ICL, Schraa, K, Aguirre-Gamboa, R, Jaeger, M, Smeekens, SP, Brand, T, Lemmers, H, Dijkstra, H, Galesloot, TE, et al
Arteriosclerosis, thrombosis, and vascular biology. 2020;(7):1787-1800
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Abstract
OBJECTIVE Metabolic dysregulation and inflammation are important consequences of obesity and impact susceptibility to cardiovascular disease. Anti-inflammatory therapy in cardiovascular disease is being developed under the assumption that inflammatory pathways are identical in women and men, but it is not known if this is indeed the case. In this study, we assessed the sex-specific relation between inflammation and metabolic dysregulation in obesity. Approach and Results: Three hundred two individuals were included, half with a BMI 27 to 30 kg/m2 and half with a BMI>30 kg/m2, 45% were women. The presence of metabolic syndrome was assessed according to the National Cholesterol Education Program-ATPIII criteria, and inflammation was studied using circulating markers of inflammation, cell counts, and ex vivo cytokine production capacity of isolated immune cells. Additionally, lipidomic and metabolomic data were gathered, and subcutaneous fat biopsies were histologically assessed. Metabolic syndrome is associated with an increased inflammatory profile that profoundly differs between women and men: women with metabolic syndrome show a lower concentration of the anti-inflammatory adiponectin, whereas men show increased levels of several pro-inflammatory markers such as IL (interleukin)-6 and leptin. Adipose tissue inflammation showed similar sex-specific associations with these markers. Peripheral blood mononuclear cells isolated from men, but not women, with metabolic syndrome display enhanced cytokine production capacity. CONCLUSIONS We identified sex-specific pathways that influence inflammation in obesity. Excessive production of proinflammatory cytokines was observed in men with metabolic syndrome. In contrast, women typically showed reduced levels of the anti-inflammatory adipokine adiponectin. These different mechanisms of inflammatory dysregulation between women and men with obesity argue for sex-specific therapeutic strategies.
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Effects of garlic supplementation on serum inflammatory markers: A systematic review and meta-analysis of randomized controlled trials.
Mirzavandi, F, Mollahosseini, M, Salehi-Abargouei, A, Makiabadi, E, Mozaffari-Khosravi, H
Diabetes & metabolic syndrome. 2020;(5):1153-1161
Abstract
BACKGROUND AND AIMS Previous studies have indicated that garlic consumption may be beneficial in improving inflammation. This systematic review and meta-analysis aimed to examine the effect of garlic supplementation on inflammatory biomarkers. METHODS PubMed/Medline, Scopus and ISI web of science were searched up to February 2019. Random effects model was used to calculate the overall effects on C-reactive protein (CRP), Interleukin-6 (IL-6), and Tumor necrosis factor- α (TNF-α). RESULTS 17 randomized controlled trials (RCTs) were included in the meta-analyses. Garlic supplementation significantly reduced the level of circulating CRP (P < 0.05), whereas it did not have any significant effect on IL-6 level (p > 0.05). Sub-group analysis showed that aged garlic extract (AGE) was able to reduce CRP and TNF-α significantly (P < 0.05). CONCLUSIONS This meta-analysis showed that supplementation with garlic could reduce the level of circulating CRP and AGE could reduce the level of TNF-α and CRP, whereas it had no significant effect on the IL-6 level.
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Prospective association of physical activity and inflammatory biomarkers in older adults from the PREDIMED-Plus study with overweight or obesity and metabolic syndrome.
Fuentes, GC, Castañer, O, Warnberg, J, Subirana, I, Buil-Cosiales, P, Salas-Salvadó, J, Corella, D, Serra-Majem, L, Romaguera, D, Estruch, R, et al
Clinical nutrition (Edinburgh, Scotland). 2020;(10):3092-3098
Abstract
BACKGROUND There is limited prospective evidence on the association between physical activity (PA) and inflammation in older adults. Our aim was to assess the associations between changes in PA and changes in the inflammatory profile in older individuals who are overweight or obese. METHODS This prospective study included 489 men and women, aged 55-75 years, from the PREDIMED-Plus trial. Levels of interleukin 6 (IL-6), interleukin 8 (IL-8), interleukin 18 (IL-18), monocyte chemo-attractant protein-1 (MCP-1), C-peptide, high-sensitivity C-reactive protein (hs-CRP), leptin, and regulated on activation, normal T-cell expressed and secreted chemokine (RANTES) were obtained from fasting blood samples and a composite inflammatory score based on these biomarkers was calculated. Physical activity was measured by a validated questionnaire. All measures were taken at baseline and one-year follow-up. RESULTS Multiple linear regression models showed an association between an increase in total PA and a decrease in the inflammatory score (p = 0.012), which was particularly driven by a decrease in C-peptide (p = 0.037). Similarly, the inflammatory score decreased with increasing moderate PA (p = 0.001), and moderate-to-vigorous PA (p = 0.006). CONCLUSIONS Increases in total PA, moderate and moderate-to-vigorous PA were associated with a decrease in the inflammatory profile of obese or overweight older individuals. This finding is relevant for PA recommendations and public health strategies. CLINICAL TRIAL REGISTRY Clinical trial identifier: International Standard Randomized Controlled Trial 89898870.
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Impact of resveratrol supplementation on inflammatory, antioxidant, and periodontal markers in type 2 diabetic patients with chronic periodontitis.
Javid, AZ, Hormoznejad, R, Yousefimanesh, HA, Haghighi-Zadeh, MH, Zakerkish, M
Diabetes & metabolic syndrome. 2019;(4):2769-2774
Abstract
BACKGROUND Diabetes mellitus and periodontal disease are two common and chronic diseases with bidirectional relationship influence public health and quality of life. The aims of this study was to study the impact of resveratrol supplementation in adjunct with non-surgical periodontal therapy on inflammatory, antioxidant, and periodontal markers in patients with type 2 diabetes with periodontal disease. MATERIALS AND METHODS In this randomized clinical trial, 43 patients with diabetes and chronic periodontitis were randomly allocated into two intervention and control groups receiving either resveratrol supplements or placebo for 4 weeks. Serum levels of interleukin 6 (IL6), tumor necrosis factor α (TNFα), total antioxidant capacity (TAC) and clinical attachment loss (CAL) as the main index of periodontal marker were measured pre-intervention and post-intervention. RESULTS In the intervention group, the mean serum level of IL6 was reduced significantly (P = 0.039) post-intervention (2.19 ± 1.09 and 1.58 ± 1.06). No significant differences were seen in the mean levels of IL6, TNFα, TAC and CAL between two groups post-intervention. CONCLUSIONS It is suggested that daily consumption of resveratrol supplement may not change TNFα, TAC and CAL, but it would be beneficial in reducing serum levels of IL6. Therefore, further studies are suggested to investigate the effects of resveratrol supplementation along with NST on periodontal status.
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The Effects of Synbiotic Supplementation on Body Mass Index, Metabolic and Inflammatory Biomarkers, and Appetite in Patients with Metabolic Syndrome: A Triple-Blind Randomized Controlled Trial.
Rabiei, S, Hedayati, M, Rashidkhani, B, Saadat, N, Shakerhossini, R
Journal of dietary supplements. 2019;(3):294-306
Abstract
It has been shown recently that metabolic syndrome is associated with gut dysbiosis. The gut microbiota may be the main target for prevention or treatment of metabolic syndrome. We investigated the effects of synbiotic supplementation on metabolic syndrome. In this triple-blinded clinical trial, 46 Iranian patients with metabolic syndrome, from both sexes, aged 25-70 years, who fulfilled inclusion criteria were randomly categorized to receive either the synbiotic or a placebo capsule, twice a day for three months, plus a weight-loss diet using stratified random sampling based on body mass index (BMI). Each synbiotic capsule consisted of seven strains probiotic bacteria (2× 108) plus fructooligosaccharide as a prebiotic. Anthropometric measurements and biochemical tests were assessed at baseline and at the end of week 12 for fasting blood sugar (FBS), insulin, lipid profile, high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), peptide YY (PYY), and glucagon-like peptide-1 (GLP-1). The mean changes of weight, BMI, FBS, insulin, homeostatic model assessment for insulin resistance (HOMA-IR), and GLP-1 between the two groups was statistically significant (p < .001). Furthermore, peptide YY (PYY) increased significantly in the synbiotic group (p ≤ .05). The trend of weight loss in the synbiotic group was significant until the end of the study (p < .001) while it stopped at week 6 in the placebo group. Synbiotic treatment may improve the status of BMI, FBS, insulin resistance, HOMA-IR, GLP-1, and PYY in patients with metabolic syndrome.
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Effect of metformin combined with lifestyle modification versus lifestyle modification alone on proinflammatory-oxidative status in drug-naïve pre-diabetic and diabetic patients: A randomized controlled study.
Bulatova, N, Kasabri, V, Qotineh, A, Al-Athami, T, Yousef, AM, AbuRuz, S, Momani, M, Zayed, A
Diabetes & metabolic syndrome. 2018;(3):257-267
Abstract
BACKGROUND Targeting biomarkers of oxidative-proinflammatory stress may result in improvement of modifiable metabolic syndrome, pre-diabetes and diabetes risk factors and subsequent risk reduction. METHODS 64 newly diagnosed antihyperglycemic treatment-naïve prediabetic and type 2 diabetes mellitus (T2DM) patients were randomly assigned using block design to either metformin combined with therapeutic lifestyle changes (TLC) or TLC alone. Body mass index (BMI), waist circumference, blood pressure, fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), fasting lipid profile, plasma oxidative status and tumor necrosis factor (TNF)-α were measured at baseline, after 3 months and after 6 months from baseline. RESULTS Except for HbA1c, baseline values did not differ significantly between the two groups. The post 3-months relative reductions in BMI (P=0.014) and HbA1c (P=0.037) in metformin combined with TLC intervention were significantly greater than those in TLC alone group. TNFα plasma levels were decreased significantly vs. baseline by metformin combined with TLC intervention (-22.90±46.76%, P=0.01). Conversely, TLC alone basically worsened proinflammatory status (42.40±40.82 %), P<0.001. Metformin with TLC treatment effected a therapeutic decrement of the oxidative stress (-15.44±35.32%, P=0.029 vs. baseline) unlike TLC alone (61.49±122.66%, P=0.01 vs. baseline). Both interventions' effects were sustained in the 6-month follow up periods. CONCLUSION In both intervention groups, the relative changes in plasma TNFα were significantly correlated (P<0.01) with systolic blood pressure and the relative changes in oxidative stress were markedly correlated (P<0.05) with total cholesterol.
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Effect of Vegan Fecal Microbiota Transplantation on Carnitine- and Choline-Derived Trimethylamine-N-Oxide Production and Vascular Inflammation in Patients With Metabolic Syndrome.
Smits, LP, Kootte, RS, Levin, E, Prodan, A, Fuentes, S, Zoetendal, EG, Wang, Z, Levison, BS, Cleophas, MCP, Kemper, EM, et al
Journal of the American Heart Association. 2018;(7)
Abstract
BACKGROUND Intestinal microbiota have been found to be linked to cardiovascular disease via conversion of the dietary compounds choline and carnitine to the atherogenic metabolite TMAO (trimethylamine-N-oxide). Specifically, a vegan diet was associated with decreased plasma TMAO levels and nearly absent TMAO production on carnitine challenge. METHODS AND RESULTS We performed a double-blind randomized controlled pilot study in which 20 male metabolic syndrome patients were randomized to single lean vegan-donor or autologous fecal microbiota transplantation. At baseline and 2 weeks thereafter, we determined the ability to produce TMAO from d6-choline and d3-carnitine (eg, labeled and unlabeled TMAO in plasma and 24-hour urine after oral ingestion of 250 mg of both isotope-labeled precursor nutrients), and fecal samples were collected for analysis of microbiota composition. 18F-fluorodeoxyglucose positron emission tomography/computed tomography scans of the abdominal aorta, as well as ex vivo peripheral blood mononuclear cell cytokine production assays, were performed. At baseline, fecal microbiota composition differed significantly between vegans and metabolic syndrome patients. With vegan-donor fecal microbiota transplantation, intestinal microbiota composition in metabolic syndrome patients, as monitored by global fecal microbial community structure, changed toward a vegan profile in some of the patients; however, no functional effects from vegan-donor fecal microbiota transplantation were seen on TMAO production, abdominal aortic 18F-fluorodeoxyglucose uptake, or ex vivo cytokine production from peripheral blood mononuclear cells. CONCLUSIONS Single lean vegan-donor fecal microbiota transplantation in metabolic syndrome patients resulted in detectable changes in intestinal microbiota composition but failed to elicit changes in TMAO production capacity or parameters related to vascular inflammation. CLINICAL TRIAL REGISTRATION URL: http://www.trialregister.nl. Unique identifier: NTR 4338.
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Yoga's effect on inflammatory biomarkers and metabolic risk factors in a high risk population - a controlled trial in primary care.
Wolff, M, Memon, AA, Chalmers, JP, Sundquist, K, Midlöv, P
BMC cardiovascular disorders. 2015;:91
Abstract
BACKGROUND Yoga can reduce blood pressure and has also been suggested to reduce inflammatory biomarkers and metabolic risk factors for cardiovascular diseases (CVDs). We aimed to assess the benefit of two yoga interventions on inflammatory biomarkers and metabolic risk factors in a high risk population in primary care. METHODS Adult patients from a health care center in Sweden, with diagnosed hypertension, were invited to undergo a baseline check at the health care center. Baseline check included standardized blood pressure measurement, BMI and weight circumference measurements, blood sampling (hs-CRP, IL-6, FP-glucose, HbA1c, cholesterol, TG, LDL and HDL) and a questionnaire on self-rated quality of life (WHOQOL-BREF). There were three groups: 1) yoga class with yoga instructor; 2) yoga at home; and 3) a control group. In total, 83 patients were included and matched at the group level for systolic blood pressure. A majority of the patients (92 %) were on antihypertensive medication, which they were requested not to change during the study. After 12 weeks of intervention, the assessments were performed again. RESULTS We recorded no evidence that yoga altered inflammatory biomarkers or metabolic risk factors in our study population. A total of 49 participants (59 %) met the criteria for metabolic syndrome. CONCLUSION The yoga interventions performed in our study did not affect inflammatory biomarkers or metabolic risk factors associated with CVD in the study population of primary care patients with hypertension. Further randomized trials are needed to elucidate the effects of yoga on CVD risk factors in this particular group. TRAIL REGISTRATION NCT01302535 , February 22, 2011.