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Serum Arylsulfatase and Acid Phosphatase Activity in Patients with Metabolic Syndrome as a Result of Oxidative Damage to Lysosomes.
Olszewska-Słonina, DM
Protein and peptide letters. 2021;(11):1246-1258
Abstract
BACKGROUND Metabolic and clinical disorders forming the complex of interrelated abnormalities is known as metabolic syndrome (METs). OBJECTIVE Our goal was to assess the dependence of serum arylsulfatase (AS) and acid phosphatase (ACP) activities on anthropometric and biochemical parameters in patients with METs. METHODS In 142 patients with METs (IDF criteria), consisting of different components in different sequences (hypertension, diabetes, lipid disorders), and in 65 healthy participants, basic biochemical parameters were determined in laboratory tests. The activity of serum hydrolases was determined using Bessey's (ACP) and Roy's (AS) methods. RESULTS The AS activity is correlated with waist-to-hip ratio (WHR) (more strongly in women and in most advanced METs), BMI (in men), and triglycerides (TG) (in women, participants with I degree obesity, and those with three METs components). The ACP activity correlated with the WHR of patients with II degree obesity, TG in those with III degree of obesity, and total cholesterol (TC) in those with four METs components. CONCLUSION Increased AS activity in patients with METs compared to lower AS activity in the control group may be due to decreased lysosomal function and related to the amount of adipose tissue. Low activity of ACP in the blood serum of patients with METs compared to high activity of ACP in the control group may indicate exhaustion of the lysosomal apparatus and loss of hydrolytic activity. The increase in TG and TC in groups with an increasing number of METs-defining components may be due to the abnormal lysosomal degradation of these compounds.
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Fecal microbial transplantation and fiber supplementation in patients with severe obesity and metabolic syndrome: a randomized double-blind, placebo-controlled phase 2 trial.
Mocanu, V, Zhang, Z, Deehan, EC, Kao, DH, Hotte, N, Karmali, S, Birch, DW, Samarasinghe, KK, Walter, J, Madsen, KL
Nature medicine. 2021;(7):1272-1279
Abstract
Fecal microbial transplantation (FMT) from lean donors to patients with obesity has been associated with metabolic benefits, yet results so far have been inconsistent. In this study, we tested the application of daily fiber supplementation as an adjunct to FMT therapy to modulate cardiometabolic outcomes. We performed a double-blind randomized trial in patients with severe obesity and metabolic syndrome receiving oral FMT, to test high-fermentable (HF) and low-fermentable (LF) fiber supplements (NCT03477916). Seventy participants were randomized to the FMT-HF (n = 17), FMT-LF (n = 17), HF (n = 17) and LF (n = 19) groups. The primary outcome was the assessment of change in insulin sensitivity from baseline to 6 weeks using the homeostatic model assessment (HOMA2-IR/IS). After 6 weeks, only patients in the FMT-LF group had significant improvements in HOMA2-IR (3.16 ± 3.01 at 6 weeks versus 3.77 ± 3.57 at baseline; P = 0.02). No difference in HOMA2-IR was observed over this period for those in the FMT-HF group (3.25 ± 1.70 at 6 weeks versus 3.17 ± 1.72 at baseline; P = 0.8), the HF group (3.49 ± 1.43 at 6 weeks versus 3.26 ± 1.33 at baseline; P = 0.8) or the LF group (3.76 ± 2.01 at 6 weeks versus 3.56 ± 1.81 at baseline; P = 0.8). Interventions were safe and well-tolerated with no treatment-attributed serious adverse events. We provide proof of concept for the use of a single-dose oral FMT combined with daily low-fermentable fiber supplementation to improve insulin sensitivity in patients with severe obesity and metabolic syndrome.
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Lifestyle Habits, Dietary Factors, and the Metabolically Unhealthy Obese Phenotype in Youth.
Roberge, JB, Van Hulst, A, Barnett, TA, Drapeau, V, Benedetti, A, Tremblay, A, Henderson, M
The Journal of pediatrics. 2019;:46-52.e1
Abstract
OBJECTIVE To determine whether lifestyle habits and dietary factors at age 8-10 years predict the development of metabolically unhealthy obesity 2 years later among children who were previously metabolically healthy obese. STUDY DESIGN The QUebec Adipose and Lifestyle InvesTigation in Youth cohort comprises 630 youth with a parental history of obesity. Metabolically healthy obesity and metabolically unhealthy obesity were defined using cut-offs for the components of pediatric metabolic syndrome. Dietary factors, physical activity, fitness, sedentary behavior, screen time, and sleep duration were measured. Multivariable logistic regressions were used to examine associations. RESULTS At baseline, 48 participants with metabolically healthy obesity were identified; 2 years later, 19 became metabolically unhealthy obese and 29 remained metabolically healthy obese. Every additional daily portion of fruits and vegetables decreased the risk of converting to metabolically unhealthy obesity by 39% (OR 0.61, 95% CI 0.40-0.94). Cumulating more hours of screen time and diets high in saturated fat and sugar-sweetened beverages and low in protein were associated with a tendency to develop metabolically unhealthy obesity. CONCLUSIONS Fruit and vegetable intake and possibly screen time, saturated fat, sugar-sweetened beverages, and protein intake may be important targets for the prevention of cardiometabolic complications in obese children. TRIAL REGISTRATION ClinicalTrials.gov: NCT03356262.
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Capacity adiposity indices to identify metabolic syndrome in subjects with intermediate cardiovascular risk (MARK study).
Gomez-Marcos, MA, Gomez-Sanchez, L, Patino-Alonso, MC, Recio-Rodriguez, JI, Gomez-Sanchez, M, Rigo, F, Marti, R, Agudo-Conde, C, Maderuelo-Fernandez, JA, Ramos, R, et al
PloS one. 2019;(1):e0209992
Abstract
BACKGROUND Obesity increases mortality, and is linked to cardiovascular diseases and metabolic syndrome (MetS). Therefore, the purpose of this study was to analyze the ability of different adiposity indices to identify subjects with MetS among people with intermediate cariovascular risk. MATERIALS AND METHODS The cross-sectional study involved 2478 subjects, recruited by the MARK study. Adiposity measures: general adiposity by body mass index (BMI), central adiposity by waist-to-height ratio (WHtR), fat mass percent by the Clínica Universidad de Navarra-body adiposity estimator (CUN-BAE), percentage of body fat and of visceral adipose tissue by body roundness index (BRI) and visceral obesity and general adiposity with body shape index (ABSI). The diagnosis of MetS was made in accordance with the criteria established in the international consensus of the Joint Scientific Statement National Cholesterol Education Program III. RESULTS The highest correlation coefficients were obtained by the glycemic components (HbA1c and FPG) of the MetS and ranged from 0.155 to 0.320. The exception was ABSI, which showed lower values in the global analysis and in the males. Values of the area under the ROC curve with the adiposity indices ranged from 0.773 with the BMI in males to 0.567 with ABSI in males. In the logistic regression analysis, all adiposity factors, except ABSI, showed similar OR values of MetS after adjusting for possible confounding factors. In the global analysis, the adiposity index that showed a highest OR of MetS was CUN-BAE (OR 5.50; 95% CI 4.27-7.09). In the analysis by gender, the highest ORs were BMI in males (OR 5.98; 95% CI 4.70-7.60) and both WHtR and BRI in females (OR 4.15; 95% CI 3.09-5.58). CONCLUSION All adiposity indices, except for ABSI, show an association with MetS and similar ability to detect subjects with MetS among people with intermediate cariovascular risk.
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A randomized controlled trial of Mediterranean diet and metformin to prevent age-related diseases in people with metabolic syndrome.
Pasanisi, P, Gargano, G, Gaetana Di Mauro, M, Cortellini, M, Casagrande, A, Villarini, A, Bruno, E, Roveda, E, Saibene, G, Venturelli, E, et al
Tumori. 2018;(2):137-142
Abstract
PURPOSE Age-related non-communicable chronic diseases (ArCDs) are the leading cause of mortality. The major metabolic risk factor for their development is the metabolic syndrome (MetS), defined as a clustering of risk factors of metabolic origin such as abdominal obesity, high blood pressure, dyslipidemia and high fasting glycemia. There is increasing observational and experimental evidence that improving diet and the use of metformin (a calorie-restriction mimetic drug) may modify the risk of developing MetS and ArCD. We designed a phase III randomized controlled trial (the Me.Me.Me trial) to evaluate the effect of a comprehensive lifestyle intervention (including moderate physical activity and a Mediterranean-macrobiotic diet) and the effect of treatment with metformin in the prevention of ArCDs in healthy people with MetS. This report describes the scientific protocol of this trial. METHODS The design of the study is 2 × 2 factorial with 2,000 volunteers to be randomized into 4 equal groups of 500 each, which are allocated to the following treatments: metformin (1,700 mg/day) + active lifestyle intervention, placebo + active lifestyle intervention, metformin (1,700 mg/day) alone, and placebo alone. The metformin/placebo component of the study is double blind. The study is planned for a term of 5 years. RESULTS The Me.Me.Me. trial is ongoing and recruitment of participants is underway. No patient has completed the 5 years of follow-up. CONCLUSIONS We believe that the results of the trial will clarify the importance of lifestyle for primary prevention and the role of metformin as a potential chemopreventive agent. The trial is registred on ClinicalTrials.gov with the identification NCT02960711.
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Diets Low in Saturated Fat with Different Unsaturated Fatty Acid Profiles Similarly Increase Serum-Mediated Cholesterol Efflux from THP-1 Macrophages in a Population with or at Risk for Metabolic Syndrome: The Canola Oil Multicenter Intervention Trial.
Liu, X, Garban, J, Jones, PJ, Vanden Heuvel, J, Lamarche, B, Jenkins, DJ, Connelly, PW, Couture, P, Pu, S, Fleming, JA, et al
The Journal of nutrition. 2018;(5):721-728
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Abstract
BACKGROUND Cholesterol efflux plays an important role in preventing atherosclerosis progression. Vegetable oils with varying unsaturated fatty acid profiles favorably affect multiple cardiovascular disease risk factors; however, their effects on cholesterol efflux remain unclear. OBJECTIVE The objectives of this study were to examine the effects of diets low in saturated fatty acids (SFAs) with varying unsaturated fatty acid profiles on serum-mediated cholesterol efflux and its association with the plasma lipophilic index and central obesity. METHODS The present study is a randomized, crossover, controlled-feeding study. Participants [men: n = 50; women: n = 51; mean ± SE age: 49.5 ± 1.2 y; body mass index (in kg/m2): 29.4 ± 0.4] at risk for or with metabolic syndrome (MetS) were randomly assigned to 5 isocaloric diets containing the treatment oils: canola oil, high oleic acid-canola oil, DHA-enriched high oleic acid-canola oil, corn oil and safflower oil blend, and flax oil and safflower oil blend. These treatment oils were incorporated into smoothies that participants consumed 2 times/d. For a 3000-kcal diet, 60 g of treatment oil was required to provide 18% of total energy per day. Each diet period was 4 wk followed by a 2- to 4-wk washout period. We quantified cholesterol efflux capacity with a validated ex vivo high-throughput cholesterol efflux assay. Statistical analyses were performed with the use of the SAS mixed-model procedure. RESULTS The 5 diets increased serum-mediated cholesterol efflux capacity from THP-1 macrophages similarly by 39%, 34%, 55%, 49% and 51%, respectively, compared with baseline (P < 0.05 for all). Waist circumference and abdominal adiposity were negatively correlated with serum-mediated cholesterol efflux capacity (r = -0.25, P = 0.01, r = -0.33, P = 0.02, respectively). CONCLUSION Diets low in SFAs with different monounsaturated fatty acid and polyunsaturated fatty acid profiles improved serum-mediated cholesterol efflux capacity in individuals with or at risk for MetS. This mechanism may account, in part, for the cardiovascular disease benefits of diets low in SFAs and high in unsaturated fatty acids. Importantly, central obesity is inversely associated with cholesterol efflux capacity. This trial was registered at www.clinicaltrials.gov as NCT01351012.
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Prevalence and characteristics of metabolic syndrome in adults from the French childhood leukemia survivors' cohort: a comparison with controls from the French population.
Oudin, C, Berbis, J, Bertrand, Y, Vercasson, C, Thomas, F, Chastagner, P, Ducassou, S, Kanold, J, Tabone, MD, Paillard, C, et al
Haematologica. 2018;(4):645-654
Abstract
The prevalence of the metabolic syndrome among adults from the French LEA childhood acute leukemia survivors' cohort was prospectively evaluated considering the type of anti-leukemic treatment received, and compared with that of controls. The metabolic profile of these patients was compared with that of controls. A total of 3203 patients from a French volunteer cohort were age- and sex-matched 3:1 to 1025 leukemia survivors (in both cohorts, mean age: 24.4 years; females: 51%). Metabolic syndrome was defined according to the National Cholesterol Education Program's Adult Treatment Panel III criteria. Metabolic syndrome was found in 10.3% of patients (mean follow-up duration: 16.3±0.2 years) and 4.5% of controls, (OR=2.49; P<0.001). Patients transplanted with total body irradiation presented the highest risk (OR=6.26; P<0.001); the other treatment groups also showed a higher risk than controls, including patients treated with chemotherapy only. Odd Ratios were 1.68 (P=0.005) after chemotherapy only, 2.32 (P=0.002) after chemotherapy and cranial irradiation, and 2.18 (P=0.057) in patients transplanted without irradiation. Total body irradiation recipients with metabolic syndrome displayed a unique profile compared with controls: smaller waist circumference (91 vs 99.6 cm; P=0.01), and increased triglyceride levels (3.99 vs 1.5 mmol/L; P<0.001), fasting glucose levels (6.2 vs 5.6 mmol/L; P=0.049), and systolic blood pressure (137.9 vs 132.8 mmHg; P=0.005). By contrast, cranial irradiation recipients with metabolic syndrome had a larger waist circumference (109 vs 99.6 cm; P=0.007) than controls. Regardless of the anti-leukemic treatment, metabolic syndrome risk was higher among childhood leukemia survivors. Its presentation differed depending on the treatment type, thus suggesting a divergent pathophysiology. This study is registered at clinicaltrials.gov identifier: 01756599.
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The 24-month metabolic benefits of the healthy living partnerships to prevent diabetes: A community-based translational study.
Pedley, CF, Case, LD, Blackwell, CS, Katula, JA, Vitolins, MZ
Diabetes & metabolic syndrome. 2018;(3):215-220
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AIMS: Large-scale clinical trials and translational studies have demonstrated that weight loss achieved through diet and physical activity reduced the development of diabetes in overweight individuals with prediabetes. These interventions also reduced the occurrence of metabolic syndrome and risk factors linked to other chronic conditions including obesity-driven cancers and cardiovascular disease. The Healthy Living Partnerships to Prevent Diabetes (HELP PD) was a clinical trial in which participants were randomized to receive a community-based lifestyle intervention translated from the Diabetes Prevention Program (DPP) or an enhanced usual care condition. The objective of this study is to compare the 12 and 24 month prevalence of metabolic syndrome in the two treatment arms of HELP PD. MATERIALS AND METHODS The intervention involved a group-based, behavioral weight-loss program led by community health workers monitored by personnel from a local diabetes education program. The enhanced usual care condition included dietary counseling and written materials. RESULTS HELP PD included 301 overweight or obese participants (BMI 25-39.9kg/m2) with elevated fasting glucose levels (95-125mg/dl). At 12 and 24 months of follow-up there were significant improvements in individual components of the metabolic syndrome: fasting blood glucose, waist circumference, HDL, triglycerides and blood pressure and the occurrence of the metabolic syndrome in the intervention group compared to the usual care group. CONCLUSIONS This study demonstrates that a community diabetes prevention program in participants with prediabetes results in metabolic benefits and a reduction in the occurrence of the metabolic syndrome in the intervention group compared to the enhanced usual care group.
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Duality of statin action on lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome: Quantity vs quality over time and implication of CETP.
Chapman, MJ, Orsoni, A, Robillard, P, Therond, P, Giral, P
Journal of clinical lipidology. 2018;(3):784-800.e4
Abstract
BACKGROUND Statins impact the metabolism, concentrations, composition, and function of circulating lipoproteins. OBJECTIVE We evaluated time course relationships between statin-mediated reduction in atherogenic apolipoprotein B (ApoB)-containing particles and dynamic intravascular remodeling of ApoAI-containing lipoprotein subpopulations in the mixed dyslipidemia of metabolic syndrome. METHODS Insulin-resistant, hypertriglyceridemic, hypercholesterolemic, obese males (n = 12) were treated with pitavastatin (4 mg/d) and response evaluated at 6, 42, and 180 days. RESULTS Reduction in low-density lipoprotein (LDL) cholesterol, ApoB, and triglycerides (TGs) was essentially complete at 42 days (-38%, -32%, and -35%, respectively); rapid reduction equally occurred in remnant cholesterol, ApoCII, CIII, and E levels (day 6; -35%, -50%, -23%, and -26%, respectively). Small dense LDLs (LDL4 and LDL5 subpopulations) predominated at baseline and were markedly reduced on treatment (-29% vs total LDL mass). Cholesteryl ester (CE) transfer protein activity and mass decreased progressively (-18% and -16%, respectively); concomitantly, TG depletion (up to -49%) and CE enrichment occurred in all high-density lipoprotein (HDL) particle subpopulations with normalization of CE/TG mass ratio at 180 days. ApoAI was redistributed from LpAI to LpAI:AII particles in HDL2a and HDL3a subpopulations; ApoCIII was preferentially depleted from LpAI:AII-rich particles on treatment. CONCLUSION Overall, statin action exhibits duality in mixed dyslipidemia, as CE transfer protein-mediated normalization of the HDL CE/TG core lags markedly behind subacute reduction in elevated levels of atherogenic ApoB-containing lipoproteins. Normalization of the HDL neutral lipid core is consistent with enhanced atheroprotective function. The HDL CE/TG ratio constitutes a metabolomic marker of perturbed HDL metabolism in insulin-resistant states, equally allowing monitoring of statin impact on HDL metabolism, structure, and function.
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Impact of the Triglyceride/High-Density Lipoprotein Cholesterol Ratio and the Hypertriglyceremic-Waist Phenotype to Predict the Metabolic Syndrome and Insulin Resistance.
von Bibra, H, Saha, S, Hapfelmeier, A, Müller, G, Schwarz, PEH
Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme. 2017;(7):542-549
Abstract
Insulin resistance is the underlying mechanism for the metabolic syndrome and associated dyslipidaemia that theoretically implies a practical tool for identifying individuals at risk for cardiovascular disease and type-2-diabetes. Another screening tool is the hypertriglyceremic-waist phenotype (HTW). There is important impact of the ethnic background but a lack of studied European populations for the association of the triglyceride/high-density lipoprotein cholesterol (HDL-C) ratio and insulin resistance. This observational, retrospective study evaluated lipid ratios and the HTW for predicting the metabolic syndrome/insulin resistance in 1932 non-diabetic individuals from Germany in the fasting state and during a glucose tolerance test. The relations of triglyceride/HDL-C, total-cholesterol/HDL-C, and low-density lipoprotein cholesterol/HDL-C with 5 surrogate estimates of insulin resistance/sensitivity and metabolic syndrome were analysed by linear regression analysis and receiver operating characteristics (ROC) in participants with normal (n=1 333) or impaired fasting glucose (n=599), also for the impact of gender. Within the lipid ratios, triglyceride/HDL-C had the strongest associations with insulin resistance/sensitivity markers. In the prediction of metabolic syndrome, diagnostic accuracy was good for triglyceride/HDL-C (area under the ROC curve 0.817) with optimal cut-off points (in mg/dl units) of 2.8 for men (80% sensitivity, 71% specificity) and 1.9 for women (80% sensitivity, 75% specificity) and fair for HTW and HOMA-IR (area under the curve 0.773 and 0.761). These data suggest the triglyceride/HDL-C ratio as a physiologically relevant and practical index for predicting the concomitant presence of metabolic syndrome, insulin resistance and dyslipidaemia for therapeutic and preventive care in apparently healthy European populations.