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Colchicine's effects on lipoprotein particle concentrations in adults with metabolic syndrome: A secondary analysis of a randomized controlled trial.

ABSTRACT: BACKGROUND:Colchicine has received renewed interest for its potential beneficial effects in secondary prevention of cardiovascular disease. This was presumed to be primarily because of its anti-inflammatory effects; however, limited data exist regarding colchicine's impact on other cardiovascular risk factors. OBJECTIVE:The aim of this study was to examine if colchicine's anti-inflammatory actions would lead to reduced circulating concentrations of oxidized low-density lipoprotein (oxLDL) in metabolically unhealthy individuals. We also examined if colchicine would improve concentrations of other atherogenic lipoprotein subfractions. METHODS:This is a secondary analysis of a double-blind, randomized, placebo-controlled pilot study in which 40 adults with metabolic syndrome were randomized to colchicine 0.6 mg or placebo twice daily for 3 months. Blood samples were collected in the fasted state. OxLDL was measured using enzyme-linked immunosorbent assay. Nuclear magnetic resonance spectroscopy was used to measure other lipoprotein particle subfraction concentrations. RESULTS:Compared with placebo, colchicine reduced markers of inflammation, including C-reactive protein, erythrocyte sedimentation rate, and GlycA (P < .01). Concentrations of oxLDL (P = .019) and small LDL (P = .022) appeared significantly increased in the colchicine arm. Colchicine had no significant effect on other lipoprotein subfractions or lipoprotein particle sizes (all P > .05). CONCLUSION:Although colchicine may have benefit in secondary prevention of cardiovascular disease in at-risk individuals, we found no evidence that these effects are because of improvements in circulating atherogenic lipoprotein particle concentrations. Further studies are needed to confirm whether colchicine increases circulating oxLDL and small LDL levels in adults with metabolic syndrome. If true, additional research is warranted to elucidate the mechanisms underlying these associations.

SUBMITTER: Demidowich AP

PROVIDER: S-EPMC6911837 | biostudies-literature | 2019 Nov - Dec

REPOSITORIES: biostudies-literature

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Colchicine's effects on lipoprotein particle concentrations in adults with metabolic syndrome: A secondary analysis of a randomized controlled trial.

Demidowich Andrew P AP Wolska Anna A Wilson Sierra R SR Levine Jordan A JA Sorokin Alexander V AV Brady Sheila M SM Remaley Alan T AT Yanovski Jack A JA

Journal of clinical lipidology 20191022 6

<h4>Background</h4>Colchicine has received renewed interest for its potential beneficial effects in secondary prevention of cardiovascular disease. This was presumed to be primarily because of its anti-inflammatory effects; however, limited data exist regarding colchicine's impact on other cardiovascular risk factors.<h4>Objective</h4>The aim of this study was to examine if colchicine's anti-inflammatory actions would lead to reduced circulating concentrations of oxidized low-density lipoprotein ...[more]

PMID: 31740368

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Project description:Aims/hypothesis: Dietary restriction (DR) reduces adiposity and improves metabolism in patients with one or more symptoms of the metabolic syndrome. Nonetheless, it remains elusive whether the benefits of DR in humans are mediated by calorie or nutrient restriction. This study was conducted to identify whether isocaloric dietary protein restriction is sufficient to confer the beneficial effects of dietary restriction in patients with metabolic syndrome. Methods: We performed a prospective, randomized controlled dietary intervention under constant nutritional and medical supervision. A total of 21 individuals diagnosed with the metabolic syndrome was randomly assigned for caloric restriction (CR; n = 11, mean age 49 ± 8.5 years, female 63%; diet of 5,941 ± 686 KJ per day) or isocaloric dietary protein restriction (PR; n = 10, mean age 51.6 ± 8.9 years, female 50%; diet of 8,409 ± 2,360 KJ per day) and followed for 27 days. Results: Like CR, PR promoted weight loss (-6.6%, P= 0.0041) due to reduction in adiposity (-9.9%, P= 0.0007), associated with reductions in blood glucose (-52.7%, P= 0.0002), lipid levels (cholesterol, -35.4%, P= 0.0010; triglycerides, -39.5% P= 0.0022) and blood pressure (systolic, -37.7 P< 0.0001; diastolic, -73.2% P< 0.0001). PR resulted in enrichment of metabolic pathways related to the immune system such as B cell proliferation, lymphocyte proliferation and leukocyte proliferation in subcutaneous adipose tissue. Hence, a reduction in calorie intake or changes in the gut microbiome are not necessary to confer the metabolic benefits of DR. Instead, a reduction in protein intake with a mild increase in carbohydrate intake to maintain the isocaloric balance of the diet is sufficient to improve metabolic control. Conclusions/interpretation: Protein restriction is sufficient to confer almost the same clinical outcomes as calorie restriction without the need for a reduction in calorie intake. The isocaloric characteristic of the PR intervention makes this approach a more attractive and less drastic dietary strategy in clinical settings and has greater potential to be used as adjuvant therapy for people with the metabolic syndrome.

Project description:BACKGROUND: Intensive lifestyle intervention significantly reduces the progression to diabetes in high-risk individuals. OBJECTIVE: It is not known whether a program of moderate intervention might effectively reduce metabolic abnormalities in the general population. DESIGN: Two-arm randomized controlled 1-year trial. PATIENTS: Three hundred and thirty-five patients participated from a dysmetabolic population-based cohort of 375 adults aged 45-64 years in northwestern Italy. MEASUREMENTS: We compared the effectiveness of a general recommendation-based program of lifestyle intervention carried out by trained professionals versus standard unstructured information given by family physicians at reducing the prevalence of multiple metabolic and inflammatory abnormalities. RESULTS: At baseline, clinical/anthropometric/laboratory and lifestyle characteristics of the intervention (n = 169) and control (n = 166) groups were not significantly different. The former significantly reduced total/saturated fat intake and increased polyunsaturated fat/fiber intake and exercise level compared to the controls. Weight, waist circumference, high-sensitivity C-reactive protein, and most of the metabolic syndrome components decreased in the intervention group and increased in the controls after 12 months. Lifestyle intervention significantly reduced metabolic syndrome (odds ratio [OR] = 0.28; 95% CI 0.18-0.44), with a 31% (21-41) absolute risk reduction, corresponding to 3.2 (2-5) patients needing to be treated to prevent 1 case after 12 months. The intervention significantly reduced the prevalence of central obesity (OR = 0.33; 0.20-0.56), and hypertriglyceridemia (OR = 0.48; 0.31-0.75) and the incidence of diabetes (OR = 0.23; 0.06-0.85). CONCLUSION: A lifestyle intervention based on general recommendations was effective in reducing multiple metabolic/inflammatory abnormalities. The usual care by family physicians was ineffective at modifying progressive metabolic deterioration in high-risk individuals.

Project description:BackgroundRecent studies indicate that participation in exercise-related games can improve executive function, attention processing, and visuospatial skills.ObjectiveThe aim of this study was to investigate whether exercise via exergaming (EXG) can improve executive function in patients with metabolic syndrome (MetS).MethodsA total of 22 MetS patients were recruited and randomly assigned to an EXG group or a treadmill exercise (TE) group. The reaction time (RT) and electrophysiological signals from the frontal (Fz), central (Cz), and parietal (Pz) cortices were collected during a Stroop task after 12 weeks of exercise.ResultsDuring the Stroop congruence (facilitation) judgment task, both the EXG and TE groups showed significantly faster RT after 12 weeks of exercise training. For N200 amplitude, the EXG group demonstrated significantly increased electrophysiological signals from the Fz and Cz cortices. These changes were significantly larger in the EXG group than in the TE group. Separately, for the P300 amplitude, the EXG groups presented significantly increased electrophysiological signals from the Fz, Cz, and Pz cortices, whereas the TE group showed significantly increased electrophysiological signals from the Cz and Pz cortices only. During the Stroop incongruence (interference) judgment task, both the EXG and TE groups showed significantly faster RT. For P300 amplitude, the EXG group had significantly increased electrophysiological signals from the Fz and Cz cortices only, whereas the TE group had significantly increased electrophysiological signals from the Fz, Cz, and Pz cortices.ConclusionsEXG improves executive function in patients with MetS as much as normal aerobic exercise does. In particular, a unique benefit of EXG beyond increased aerobic capacity is the improved selective attention among cognitive functions. Thus, EXG could be recommended to someone who needs to improve their brain responses of concentration and judgment as well as physical fitness.Trial registrationClinicalTrials.gov NCT04015583; https://clinicaltrials.gov/ct2/show/NCT04015583.

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Colchicine's effects on lipoprotein particle concentrations in adults with metabolic syndrome: A secondary analysis of a randomized controlled trial.

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Colchicine's effects on lipoprotein particle concentrations in adults with metabolic syndrome: A secondary analysis of a randomized controlled trial.

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