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Colchicine's effects on metabolic and inflammatory molecules in adults with obesity and metabolic syndrome: results from a pilot randomized controlled trial.

ABSTRACT: OBJECTIVE:Recent clinical trials have demonstrated that colchicine may have metabolic and cardiovascular and benefits in at-risk patients; however, the mechanisms through which colchicine may improve outcomes are still unclear. We sought to examine colchicine's effects on circulating inflammatory and metabolic molecules in adults with obesity and metabolic syndrome (MetS). METHODS:Blood samples were collected pre- and post-intervention during a double-blind randomized controlled trial in which 40 adults with obesity and MetS were randomized to colchicine 0.6?mg or placebo twice-daily for 3 months. Serum samples were analyzed for 1305 circulating factors using the SomaScan Platform. The Benjamini-Hochberg procedure was used to adjust the false discovery rate (FDR) for multiple testing. RESULTS:At baseline, age (48.0?±?13.8 vs. 44.7?±?10.3 years) and BMI (39.8?±?6.4 vs. 41.8?±?8.2?kg/m2) were not different between groups. After controlling for the FDR, 34 molecules were significantly changed by colchicine. Colchicine decreased concentrations of multiple inflammatory molecules, including C-reactive protein, interleukin 6, and resistin, in addition to vascular-related proteins (e.g., oxidized low-density lipoprotein receptor, phosphodiesterase 5A). Conversely, relative to placebo, colchicine significantly increased concentrations of eight molecules including secreted factors associated with metabolism and anti-thrombosis. CONCLUSIONS:In adults with obesity, colchicine significantly affected concentrations of proteins involved in the innate immune system, endothelial function and atherosclerosis, uncovering new mechanisms behind its cardiometabolic effects. Further research is warranted to investigate whether colchicine's IL-6 suppressive effects may be beneficial in COVID-19.

SUBMITTER: Demidowich AP

PROVIDER: S-EPMC7253147 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Colchicine's effects on metabolic and inflammatory molecules in adults with obesity and metabolic syndrome: results from a pilot randomized controlled trial.

Demidowich Andrew P AP Levine Jordan A JA Apps Richard R Cheung Foo K FK Chen Jinguo J Fantoni Giovanna G Patel Tushar P TP Yanovski Jack A JA

International journal of obesity (2005) 20200527 8

<h4>Objective</h4>Recent clinical trials have demonstrated that colchicine may have metabolic and cardiovascular and benefits in at-risk patients; however, the mechanisms through which colchicine may improve outcomes are still unclear. We sought to examine colchicine's effects on circulating inflammatory and metabolic molecules in adults with obesity and metabolic syndrome (MetS).<h4>Methods</h4>Blood samples were collected pre- and post-intervention during a double-blind randomized controlled t ...[more]

PMID: 32461554

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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: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.

Project description:The objective of this study was to determine the ability of either aerobic or resistance training to counter weight-loss-associated bone loss in older adults. There were 187 older adults (67 years, 70% women, 64% white) with obesity (BMI = 34.5 ± 3.7 kg/m2 ) and cardiovascular disease and/or metabolic syndrome who were randomized to participate in an 18-month, community-based trial, with a follow-up assessment at 30 months. Intervention arms included: weight loss alone (WL; 7% to 10% baseline weight), WL plus aerobic training (WL + AT), and WL plus resistance training (WL + RT), as well as DXA-acquired total hip, femoral neck, and lumbar spine areal bone mineral density (aBMD), and trabecular bone score (TBS). Biomarkers of bone turnover (procollagen type 1 N-terminal propeptide, C-terminal telopeptide of type 1 collagen) were measured at baseline, 6, 18, and 30 (aBMD and TBS only) months. CT-acquired hip and spine volumetric BMD (vBMD), cortical thickness, and bone strength were measured in a subset at baseline (n = 55) and 18 months. Total hip aBMD was reduced by 2% in all groups at 18 months, with a primary analysis showing no significant treatment effects for any DXA, biomarker, or CT outcome. After adjustment for WL and follow-up at 30 months, secondary analyses revealed that total hip [-0.018 (-0.023 to -0.012) g/cm2 versus -0.025 (-0.031 to -0.019) g/cm2 ; p = 0.05] and femoral neck [-0.01 (-0.009 to 0.008) g/cm2 versus -0.011 (-0.020 to -0.002) g/cm2 ; p = 0.06] aBMD estimates were modestly attenuated in the WL + RT group compared with the WL group. Additionally, lumbar spine aBMD was increased in the WL [0.015 (0.007 to 0.024) g/cm2 ] and the WL + RT [0.009 (0.000 to 0.017) g/cm2 ] groups compared with the WL + AT [-0.003 (-0.012 to 0.005)g/cm2 ] group; both p ≤ 0.01. Community-based exercise does not prevent bone loss during active WL in older adults; however, adding RT may help minimize long-term hip bone loss. © 2018 American Society for Bone and Mineral Research.

Project description:IntroductionResistance to initiating insulin therapy is common for people with type 2 diabetes (T2D) using multiple oral agents, resulting in sustained poor glycemic control. We explored a non-pharmacologic option and examined whether adults with T2D and elevated hemoglobin A1c (HbA1c) who were using multiple, non-insulin antihyperglycemics could obtain glycemic benefit from limited, episodic use of real-time continuous glucose monitoring (rtCGM).MethodsA randomized, pilot trial enrolled patients with T2D who were using two or more non-insulin therapies and had HbA1c values of 7.8-10.5%. Following a baseline, 10-day, blinded CGM session, participants were randomized 2:1, rtCGM or self-monitoring of blood glucose (SMBG). Medication changes were not made during the 12-week study unless required for safety; benefits would result from lifestyle changes. The rtCGM group used unblinded rtCGM for three sessions at weeks 0, 4, and 8, and the control group managed diabetes with SMBG and wore blinded rtCGM at week 8. Glycemic endpoints were assessed.ResultsSeventy participants were enrolled from eight North American sites and data were available from 68 (n = 45 rtCGM; n = 23 SMBG). Median (IQR) baseline HbA1c was 8.4 (0.8)% and 8.3 (1.2)% and median (IQR) change in HbA1c at week 12 was - 0.5 (1.3)% and - 0.2 (1.1)% for the rtCGM and SMBG groups, respectively (between-group difference p = 0.74). More than one-third (34.1%) of the rtCGM group vs 17.4% of the SMBG group reached the HbA1c goal of less than 7.5% at week 12 (between-group difference p = 0.12). Compared to run-in, mean (SD) time in range (TIR 70-180 mg/dL) at week 8 increased for the rtCGM group (56.3 [24.5]% vs 63.1 [25.5]%) while it decreased for the SMBG group (68.4 [21.5]% vs 55.1 [30.3]%). HbA1c reductions were not sustained at month 9.ConclusionIn this pilot study, limited episodic rtCGM use in people failing multiple non-insulin therapies resulted in modest, short-term glycemic benefits.

Project description:BACKGROUND:Metabolic syndrome (MetS) is defined as the presence of central obesity plus any two of the following markers: high triglycerides (>?150 mg/dl), low high density lipoprotein (HDL) cholesterol <?40 mg/dl in men and?<?50 mg/dl in women, hypertension (blood pressure?>?130/85 mmHg or use of antihypertensive medication), high fasting blood glucose (>?100 mg/dl or use of treatment for diabetes mellitus). Since recently, metabolic syndrome and obesity have become emerging problems of both low and middle income countries, although they have been the leading cause of morbidity and mortality in high income countries for the past decades. It has been indicated that the international anthropometric cut-off for detecting obesity is not appropriate for Ethiopians. This study developed optimal cut off values for anthropometric indicators of obesity and markers of metabolic syndrome for Ethiopian adults to enhance preventive interventions. METHODS:A total of 704 employees of Jimma University were randomly selected using their payroll as a sampling frame. Data on socio-demographic, anthropometry, clinical and blood samples were collected from February to April 2015. Receiver Operating Characteristic Curve analyses were used to determine optimal anthropometric cut-off values for obesity and markers of the metabolic syndrome. WHO indicators of obesity based on body fat percent (>?25% for males and?>?35% for females) were used as binary classifiers for developing anthropometric cut-offs. Optimal cut-off values were presented using sensitivity, specificity and area under the curve. RESULTS:The optimal cut-off for obesity using body mass index was 22.2 k/m2 for males and 24.5 kg/m2 for females. Similarly, the optimal waist circumference cut-off for obesity was 83.7 cm for males and 78.0 cm for females. The cut-off values for detecting obesity using waist to hip ratio and waist to height ratio were: WHR (0.88) and WHtR (0.49) for males, while they were 0.82 and 0.50 for females, respectively. Anthropometric cut-off values for markers of metabolic syndrome were lower compared to the international values. For females, the optimal BMI cut-offs for metabolic syndrome markers ranged from 24.8 kg/m2 (triglycerides) to 26.8 kg/m2 (fasting blood sugar). For WC the optimal cut-off ranged from of 82.1 cm (triglyceride) to 96.0 cm(HDL); while for WHtR the optimal values varied from 0.47(HDL) to 0.56(fasting blood sugar). Likewise, the optimal cut-offs of WHR for markers of metabolic syndrome ranged from 0.78(fasting blood sugar) to 0.89(HDL and blood pressure). For males, the optimal BMI cut-offs for metabolic syndrome markers ranged from 21.0 kg/m2 (HDL) to 23.5 kg/m2 (blood pressure). For WC, the optimal cut-off ranged from 85.3 cm (triglyceride) to 96.0 cm(fasting blood sugar); while for WHtR the optimal values varied from 0.47(BP, FBS and HDL) to 0.53(Triglyceride). Similarly, the optimal cut-offs of WHR form markers of metabolic syndrome ranged from 0.86(blood pressure) to 0.95(fasting blood sugar). CONCLUSION:The optimal anthropometric cut-offs for obesity and markers of metabolic syndrome in Ethiopian adults are lower than the international values. The findings imply that the international cut-off for WC, WHtR, WHR and BMI underestimate obesity and metabolic syndrome markers among Ethiopian adults, which should be considered in developing intervention strategies. It is recommended to use the new cut-offs for public health interventions to curb the increasing magnitude of obesity and associated metabolic syndrome and diet related non-communicable diseases in Ethiopia.

Dataset Information

Colchicine's effects on metabolic and inflammatory molecules in adults with obesity and metabolic syndrome: results from a pilot randomized controlled trial.

Publications

Colchicine's effects on metabolic and inflammatory molecules in adults with obesity and metabolic syndrome: results from a pilot randomized controlled trial.

Similar Datasets

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