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Liraglutide in combination with metformin may improve the atherogenic lipid profile and decrease C-reactive protein level in statin treated obese patients with coronary artery disease and newly diagnosed type 2 diabetes: A randomized trial.
Anholm, C, Kumarathurai, P, Pedersen, LR, Samkani, A, Walzem, RL, Nielsen, OW, Kristiansen, OP, Fenger, M, Madsbad, S, Sajadieh, A, et al
Atherosclerosis. 2019;:60-66
Abstract
BACKGROUND AND AIMS Atherosclerosis in obesity and type 2 diabetes (T2DM) is associated with low-grade inflammation (LGI) and dyslipidemia, where especially small, dense lipoprotein particles are atherogenic. The glucagon-like peptide-1 receptor agonist, liraglutide, reduces cardiovascular events by poorly understood mechanisms. We investigated the effect of liraglutide combined with metformin on LGI and lipoprotein density profiles in patients with stable coronary artery disease (CAD) and newly diagnosed T2DM. METHODS We conducted a randomized, double-blind, placebo-controlled, cross-over trial over a 12 + 12-week period, with ≥2-week wash-out. INTERVENTION liraglutide/metformin vs. placebo/metformin. Lipoproteins were separated by continuous density gradient ultracentrifugation, and LDL divided into five subfractions between 226 and 270 Å, considering particle size ≤255 Å as the atherogenic pattern. Plasma C-reactive protein and tumor necrosis factor-α were assessed by the enzyme-linked immunosorbent-assay. RESULTS 28 out of 41 randomized patients completed all visits. Intention-to-treat analysis was performed but one patient had statin dosage and was excluded from the analysis. 95% of the patients were on statin therapy. Overall, liraglutide did not affect lipid subfractions or markers of LGI compared to placebo. The combination of liraglutide and metformin reduced the total LDL subfractions, primarily by reducing the most atherogenic subfraction LDL5, and reduced CRP but not TNF-α. Explorative analyses suggested that the subfraction LDL5 during the wash-out period rebounded significantly at least in a per-protocol analysis of the sub-group of patients starting the liraglutide therapy. CONCLUSIONS In patients with CAD and newly diagnosed T2DM on stable statin therapy, liraglutide combined with metformin may improve the atherogenic LDL lipid profile and CRP.
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Effects of cholecalciferol supplementation on inflammatory markers and muscle damage indices of soccer players after a simulated soccer match.
Parsaie, N, Ghavamzadeh, S, Cheraghi, M
Nutrition (Burbank, Los Angeles County, Calif.). 2019;:37-43
Abstract
OBJECTIVES Soccer-induced muscle damage and inflammation lead to a reduction in athletic performance. The aim of this study was to determine whether supplementation with cholecalciferol would reduce inflammation and muscle damage in soccer players after a simulated soccer match. METHODS Twenty-two soccer players (median age 27 y, interquartile range 5 y) were divided randomly into two groups, as follows: a cholecalciferol group (n = 11) and a placebo group (n = 11). Cholecalciferol supplements (50 000 IU/wk) or placebos were administered to the groups by an independent co-worker. After 8 wk, the athletes participated in a simulated soccer match, and perceived exertion and heart rates were measured during the trial. Blood samples were obtained presupplementation, postsupplementation, immediately after, and 2- and 24-h postexercise for measurement of lactate dehydrogenase, creatine phosphokinase, C-reactive protein (CRP), and interleukin (IL)-6. RESULTS The intervention group demonstrated a significant increase in serum 25-hydroxyvitamin D levels (53.93, 10.68 ng/mL, P < 0.0001), which is the best indicator of vitamin D levels in the body, with no change in the circulating markers of muscle damage and CRP (P ˃ 0.05) but showed increased IL-6 (P = 0.034). In addition, the ratings of perceived exertion and heart rates were not altered by vitamin D compared with placebo ingestion (P = 0.155 versus P = 0.261; P = 0.600 versus P = 0.983). CONCLUSION The study showed that 50 000 IU/wk of cholecalciferol supplementation for 8 wk increased the 25-hydroxyvitamin D levels, with no effect on muscle damage indices or CRP. However, The IL-6 concentration was generally higher in the intervention group.
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Effects of 1 year of exercise training versus combined exercise training and weight loss on body composition, low-grade inflammation and lipids in overweight patients with coronary artery disease: a randomized trial.
Pedersen, LR, Olsen, RH, Anholm, C, Astrup, A, Eugen-Olsen, J, Fenger, M, Simonsen, L, Walzem, RL, Haugaard, SB, Prescott, E
Cardiovascular diabetology. 2019;(1):127
Abstract
BACKGROUND Dyslipidaemia and low-grade inflammation are central in atherogenesis and linked to overweight and physical inactivity. Lifestyle changes are important in secondary prevention of coronary artery disease (CAD). We compared the effects of combined weight loss and interval training with interval training alone on physical fitness, body composition, dyslipidaemia and low-grade inflammation in overweight, sedentary participants with CAD. METHODS Seventy CAD patients, BMI 28-40 kg/m2 and age 45-75 years were randomised to (1) 12 weeks' aerobic interval training (AIT) at 90% of peak heart rate three times/week followed by 40 weeks' AIT twice weekly or (2) a low energy diet (LED) (800-1000 kcal/day) for 8-10 weeks followed by 40 weeks' weight maintenance including AIT twice weekly and a high-protein/low-glycaemic load diet. Effects of the intervention were evaluated by physical fitness, body weight and composition. Dyslipidaemia was described using both biochemical analysis of lipid concentrations and lipoprotein particle subclass distribution determined by density profiling. Low-grade inflammation was determined by C-reactive protein, soluble urokinase-type plasminogen activator receptor and tumour necrosis factor α. Effects on continuous outcomes were tested by mixed-models analysis. RESULTS Twenty-six (74%) AIT and 29 (83%) LED + AIT participants completed the study. At baseline subject included 43 (78%) men; subjects averages were: age 63 years (6.2), body weight 95.9 kg (12.2) and VO2peak 20.7 mL O2/kg/min (4.9). Forty-six (84%) had pre-diabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance). LED + AIT reduced body weight by 7.2 kg (- 8.4; - 6.1) and waist circumference by 6.6 cm (- 7.7; - 5.5) compared to 1.7 kg (- 0.7; - 2.6) and 3.3 cm (- 5.1; - 1.5) after AIT (within-group p < 0.001, between-group p < 0.001 and p = 0.018, respectively). Treatments caused similar changes in VO2peak and lowering of total cholesterol, triglycerides, non-HDL cholesterol and low-grade inflammation. A shift toward larger HDL particles was seen following LED + AIT while AIT elicited no change. CONCLUSIONS Both interventions were feasible. Both groups obtained improvements in VO2peak, serum-lipids and inflammation with superior weight loss and greater central fat loss following LED + AIT. Combined LED induced weight loss and exercise can be recommended to CAD patients. Trial registration NCT01724567, November 12, 2012, retrospectively registered (enrolment ended in April 2013).
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Associations between Dietary Acid Load and Biomarkers of Inflammation and Hyperglycemia in Breast Cancer Survivors.
Wu, T, Seaver, P, Lemus, H, Hollenbach, K, Wang, E, Pierce, JP
Nutrients. 2019;(8)
Abstract
Metabolic acidosis can lead to inflammation, tissue damage, and cancer metastasis. Dietary acid load contributes to metabolic acidosis if endogenous acid-base balance is not properly regulated. Breast cancer survivors have reduced capacities to adjust their acid-base balance; yet, the associations between dietary acid load and inflammation and hyperglycemia have not been examined among them. We analyzed data collected from 3042 breast cancer survivors enrolled in the Women's Healthy Eating and Living (WHEL) Study who had provided detailed dietary intakes and measurements of plasma C-reactive protein (CRP) and hemoglobin A1c (HbA1c). Using a cross-sectional design, we found positive associations between dietary acid load and plasma CRP and HbA1c. In the multivariable-adjusted models, compared to women with the lowest quartile, the intakes of dietary acid load among women with the highest quartile showed 30-33% increases of CRP and 6-9% increases of HbA1c. Our study is the first to demonstrate positive associations between dietary acid load and CRP and HbA1c in breast cancer survivors. Our study identifies a novel dietary factor that may lead to inflammation and hyperglycemia, both of which are strong risk factors for breast cancer recurrence and comorbidities.
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The role of hormonal, metabolic and inflammatory biomarkers on sleep and appetite in drug free patients with major depression: A systematic review.
Caroleo, M, Carbone, EA, Primerano, A, Foti, D, Brunetti, A, Segura-Garcia, C
Journal of affective disorders. 2019;:249-259
Abstract
BACKGROUND Major depressive disorder (MDD) is a complex and heterogeneous disorder in which clinical symptoms can widely differ among patients. Neurovegetative symptoms, i.e. decreased or increased appetite, changes in body weight and sleep disturbances, described as 'melancholic' or 'atypical' features of a depressive episode, are the most variable symptoms among patients with MDD. We hypothesized biomarkers differences underlying this neurovegetative variability in major depression. METHODS We systematically reviewed, according to the PRISMA guidelines, the role of specific metabolic, hormonal and inflammatory biomarkers in drug-free MDD patients, that could have neurobiological effects on appetite, weight regulation and circadian rhythms, influencing eating behaviour and sleep patterns. All studies regarding the co-occurrence of disturbed sleep and appetite were examined. RESULTS Besides the well-known leptin and ghrelin, other biomarkers such as BDNF, VEGF, NPY, orexin, and the recent discovered nesfatin-1 seem to be involved in neurovegetative changes in depressive disorders playing a role in the regulation of affective states, stress reactions and sleep patterns. Interestingly, based on the existing evidence, ghrelin, orexin and nesfatin-1 could be linked both to sleep and appetite regulation in depressed patients. LIMITATIONS Heterogeneous studies with low sample size. CONCLUSIONS Despite the wide heterogeneity of results, studies on biomarkers of appetite and sleep in MDD are an interesting field of research to explain the neurobiological substrates of depressive symptoms that deserve further investigation.
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Effect of Bariatric Surgery on Serum Inflammatory Factors of Obese Patients: a Systematic Review and Meta-Analysis.
Askarpour, M, Khani, D, Sheikhi, A, Ghaedi, E, Alizadeh, S
Obesity surgery. 2019;(8):2631-2647
Abstract
Obesity is one of the main causes of inflammation. Previous studies have reported inconclusive results regarding the effect of bariatric surgery on inflammatory markers. This systematic review and meta-analysis is aimed at describing the effect of bariatric surgery on C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α). PubMed/Medline and Scopus were systematically searched for all eligible studies from inception to June 2018. Results are expressed as weighted mean difference (MD) with 95% confidence intervals (CI) using a random effects model. Overall, 116 studies which evaluated serum CRP, IL-6, and TNF-α after bariatric surgery were included. Pooled effect size showed significant reduction in serum CRP (- 5.30 mg/l, 95% CI - 5.46, - 5.15, P < 0.001), IL-6 (- 0.58 pg/ml, 95% CI - 0.64, - 0.53, P < 0.001), and TNF-α (- 0.20 pg/ml, 95% CI - 0.39, - 0.02, P = 0.031) with significant heterogeneity across studies (> 95% for all factors). Bariatric surgery significantly lowered inflammatory factors; however, baseline BMI, follow-up duration and type of surgery could impact the extent of observed effects.
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Vegetarian-Based Dietary Patterns and their Relation with Inflammatory and Immune Biomarkers: A Systematic Review and Meta-Analysis.
Craddock, JC, Neale, EP, Peoples, GE, Probst, YC
Advances in nutrition (Bethesda, Md.). 2019;(3):433-451
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Abstract
Dietary patterns with substantial proportions of energy from plant sources have been associated with favorable biomarkers of low-grade inflammation. Less is known of the relation between vegetarian-based dietary patterns and markers of inflammation and immune status. This systematic review and meta-analysis aimed to determine the relation between vegetarian-based dietary patterns and inflammatory and immune markers (C-reactive protein, tumour necrosis factor α, fibrinogen, natural killer cells, leukocytes, lymphocytes, thrombocytes, interleukins, and immunoglobulins). PubMed, Medline, and Cochrane scientific databases were searched to identify relevant studies. Random effects meta-analyses were conducted to assess the weighted mean differences (WMDs) for each outcome variable between vegetarian and non-vegetarian groups. Thirty observational and 10 intervention studies were included in the review. Pooled effects of vegetarian-based dietary patterns were associated with significantly lower concentrations of CRP (WMD: -0.61 mg/L; 95% CI: -0.91, -0.32 mg/L; P = 0.0001), fibrinogen (WMD: -0.22 g/L; 95% CI: -0.41, -0.04 mg/L; P = 0.02), and total leukocyte (WMD: -0.62 × 10(3)/μL; 95% CI -1.13 × 10(3), -0.10 × 10(3)/μL; P = 0.02) compared with those following non-vegetarian dietary patterns in observational studies. Insufficient data were identified for a meta-analysis of intervention studies. This study provides evidence that vegetarian-based dietary patterns are associated with lowered serum C-reactive protein, fibrinogen, and total leukocyte concentrations. Future research should focus on large-scale intervention trials, contrasting differences in inflammation and immune status and function between vegetarian and non-vegetarian-based populations.
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Effects of flaxseed and flaxseed oil supplement on serum levels of inflammatory markers, metabolic parameters and severity of disease in patients with ulcerative colitis.
Morshedzadeh, N, Shahrokh, S, Aghdaei, HA, Amin Pourhoseingholi, M, Chaleshi, V, Hekmatdoost, A, Karimi, S, Zali, MR, Mirmiran, P
Complementary therapies in medicine. 2019;:36-43
Abstract
OBJECTIVE The present study aimed to evaluate the possible effect of grounded flaxseed and flaxseed oil on serum levels of inflammatory markers, metabolic parameters, and the severity of disease in patients with UC. METHODS In this open-labeled randomized controlled trial, 90 UC patients were randomly assigned to one of the 3 groups for 12 weeks: grounded flaxseed (GF; 30 g/day), flaxseed oil (FO; 10 g/day) and control group. The weight, waist circumference, systolic and diastolic blood pressure, serum inflammatory markers (interleukin-6 (IL-6), interferon gamma (INF-γ), transforming growth factor beta (TGF-β), and Erythrocyte Sedimentation Rate (ESR)), and fecal calprotectin were measured at the baseline and end of the study. RESULTS Totally, 75 patients (43 men and 32 women) with a mean age of 31.54 ± 9.84 years participated in the present study. Comparing the change of the variables indicated a significant decrease in fecal calprotectin (P < 0.001), Mayo score (P < 0.001), ESR (P < 0.001), INF-γ (P < 0.001), IL-6 (P < 0.001), waist circumference (P = 0.02), Diastolic Blood Pressure (DBP) (P < 0.001), and Systolic Blood Pressure (SBP) (P < 0.001) and a significant increase in TGF-β (P < 0.001) and Inflammatory Bowel Disease Questionnaire-Short form (IBDQ-9) score (P < 0.001) in the GF and FO groups compared to the control. No difference was obvious between the FO and GF groups except for TGF-β. CONCLUSION The present study showed that both flaxseed and flaxseed oil, attenuate inflammatory markers, disease severity, blood pressure, and WC. However, the effect of flaxseed on weight and BMI was not evident.
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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.