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The Effect of Exercise Intensity and Volume on Metabolic Phenotype in Patients with Metabolic Syndrome: A Randomized Controlled Trial.
von Korn, P, Keating, S, Mueller, S, Haller, B, Kraenkel, N, Dinges, S, Duvinage, A, Scherr, J, Wisløff, U, Tjønna, AE, et al
Metabolic syndrome and related disorders. 2021;(2):107-114
Abstract
Background: Moderate intensity continuous training (MICT) ameliorates dysmetabolism in patients with metabolic syndrome (MetS). The impact of low- (1HIIT) versus high-volume high-intensity interval training (4HIIT) versus MICT on central adiposity, insulin resistance, and atherogenic dyslipidemia in patients with MetS has not yet been reported. Methods: Twenty-nine patients with MetS according to International Diabetes Federation criteria (nine females, age 61 ± 5 years, body mass index 31.1 ± 3.7 kg/m2, waist circumference (WC) ♀ 102.2 ± 10.6 cm, ♂ 108.5 ± 8.6 cm) were randomized (1:1:1) to 16 weeks of (1) MICT (5 × 30 min/week, 35%-50% heart rate reserve (HRR), (2) 1HIIT (3 × 17 min/week incl. 4 min @80%-90% HRR), and (3) 4HIIT (3 × 38 min/week incl. 4 × 4 min @80%-90% HRR). Peak oxygen uptake (V̇O2peak), WC and anthropometric/metabolic indices indicative of MetS, fasting glucose/insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), dyslipidemia, and respiratory exchange ratio (RER) at warm-up were quantified at baseline and study completion. Analysis of variance and paired t tests were used for statistical analysis. Analyses were performed after checking for parametric distribution. Results: There were no significant differences between groups in waist-to-height ratio (♀: Δ -0.10 ± -0.05, ♂: Δ -0.08 ± -0.06, P = 0.916), WC (♀: Δ -1.4 ± -0.1 cm, ♂: Δ 0.1 ± 0.9 cm, P = 0.590), fasting glucose (Δ -1.18 ± 16.7 μU/mL, P = 0.773), fasting insulin (Δ 0.76 ± 13.4 μU/mL, P = 0.509), HOMA-IR (Δ 0.55 ± 4.1, P = 0.158), atherogenic dyslipidemia [triglycerides (TAG) Δ -10.1 ± 46.9 mg/dL, P = 0.468, high-density lipoprotein cholesterol (HDL-C) Δ 1.5 ± 5.4, P = 0.665, TAG/HDL-C -0.19 ± 1.3, P = 0.502], V̇O2peak (P = 0.999), or RER (P = 0.842). In the entire group, waist-to-height-ratio and V̇O2peak significantly improved by a clinically meaningful amount (Δ 2.7 ± 0.9 mL/min/kg; P < 0.001) and RER at warm-up significantly decreased (Δ -0.03 ± 0.06, P = 0.039). Conclusion: In patients with MetS, there was no significant difference between HIIT, irrespective of volume, to MICT for improving exercise capacity or metabolic health.
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Mechanisms of action of duodenal mucosal resurfacing in insulin resistant women with polycystic ovary syndrome.
Kaur, V, Dimitriadis, GK, Pérez-Pevida, B, Bansi, DS, Jayasena, C, Bate, D, Houghton, R, Fielding, BA, Balfoussia, D, Webber, L, et al
Metabolism: clinical and experimental. 2021;:154908
Abstract
BACKGROUND Duodenal mucosal resurfacing (DMR) is a novel day-case endoscopic intervention which results in weight loss-independent reductions in HbA1c in patient with type 2 diabetes mellitus (T2DM). We hypothesized that DMR works by increasing insulin sensitivity and we aimed to investigate the mechanism of action of DMR through longitudinal metabolic phenotyping in humans. METHODS Thirty-two insulin-resistant women with polycystic ovary syndrome (PCOS) and obesity were randomised in a double-blinded manner to DMR or sham endoscopy. They underwent measurements of insulin sensitivity using euglycaemic hyperinsulinaemic clamps, insulin secretion using oral glucose tolerance tests and reproductive function using weekly reproductive hormone profiles and ovarian ultrasonography for 6 months post-intervention. RESULTS A small increase in total body insulin sensitivity measured by the clamp was observed in both groups at week 12. An increase in insulin sensitivity, as measured by HOMA-IR, was observed in both groups at week 24. There was an increase in the number of menses (median 2 DMR, 0.5 sham). There were no significant differences between the two groups in these outcomes or insulin secretion. CONCLUSIONS These findings suggest that DMR does not work by increasing insulin sensitivity in euglycaemic, insulin resistant women with PCOS. The procedure may exert its effects only in the context of hyperglycaemia or pathologically hyperplastic, insulin-desensitised duodenal mucosa.
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Randomized double blind clinical trial evaluating the Ellagic acid effects on insulin resistance, oxidative stress and sex hormones levels in women with polycystic ovarian syndrome.
Kazemi, M, Lalooha, F, Nooshabadi, MR, Dashti, F, Kavianpour, M, Haghighian, HK
Journal of ovarian research. 2021;(1):100
Abstract
OBJECTIVE The design of this study was due to the report of the antioxidant properties of Ellagic acid (EA) for its evaluation on the Insulin resistance (IR), oxidative stress and sex hormones levels in women with polycystic ovarian syndrome (PCOS). METHODS In this randomized, double-blind, placebo-controlled clinical trial, 60 patients were recruited. Patients were randomly allocated consumed a capsule containing 200 mg of EA per day (n = 30) or placebo (n = 30) for 8 weeks. The fasting blood sugar (FBS), insulin, IR, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL), high density lipoprotein (HDL), total antioxidant capacity (TAC), Malondialdehyde (MDA), C-reactive protein (CRP), Tumor necrosis factor-alpha (TNF-α), sex hormones and anti-mullerian hormone (AMH) were measured at the beginning and end of the study. RESULT At the end of the study, the mean of FBS, insulin, IR, TC, TG, LDL, MDA, CRP, TNF-α, total testosterone, prolactin and AMH were significantly decreased in the intervention group compared to the placebo group (P < 0.05). Also, there was a significant increase in the mean of TAC after supplementation with EA (P < 0.05). At the end of the study, no significant changes were observed in the mean of anthropometric factors, physical activity and food intake (P > 0.05). CONCLUSION EA supplementation can be helpful as a diet supplement in women with PCOS through improvement in insulin resistance. This supplement may be used to reduce metabolic disorders in women. TRIAL REGISTRATION This study was retrospectively (07-07-2019) registered in the Iranian website ( www.irct.ir ) for registration of clinical trials ( IRCT20141025019669N12 ).
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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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Hypoxia and exercise interactions on skeletal muscle insulin sensitivity in obese subjects with metabolic syndrome: results of a randomized controlled trial.
Mai, K, Klug, L, Rakova, N, Piper, SK, Mähler, A, Bobbert, T, Schulz-Menger, J, Spranger, J, Boschmann, M, Luft, FC
International journal of obesity (2005). 2020;(5):1119-1128
Abstract
BACKGROUND Physical activity improves insulin sensitivity in obesity. Hypoxia training is claimed to augment this effect. We tested the hypothesis that normobaric hypoxia training would improve insulin sensitivity in obese patients with metabolic syndrome. METHODS In a randomized controlled trial, 23 obese men with metabolic syndrome who were not informed of the FiO2 conditions underwent a 6-week physical exercise intervention under ambient (n = 11; FiO2 21%) conditions or hypoxia (n = 12; FiO2 15%) using a normobaric hypoxic chamber. Three 60-min sessions of interval training were performed each week at 60% of individual V̇O2max. Assessment of myocellular insulin sensitivity by euglycemic hyperinsulinemic clamp was performed in 21 of these subjects before and after 6 weeks of training. Comprehensive phenotyping also included biopsies of subcutaneous adipose tissues. RESULTS The intermittent moderate physical exercise protocol did not substantially change the myocellular insulin sensitivity within 6 weeks under normoxic conditions (ISIClamp: 0.035 (IQR 0.016-0.075) vs. 0.037 (IQR 0.026-0.056) mg* kg-1 *min-1/(mU* l-1); p = 0.767). In contrast, ISIClamp improved during hypoxia training (0.028 (IQR 0.018-0.035) vs. 0.038 (IQR 0.024-0.060) mg * kg-1 *min-1/(mU *l-1); p < 0.05). Between group comparison of ISIClamp change revealed a small difference between groups (Cohen's d = 0.26). Within the hypoxic group, improvement of ISIClamp during training was associated with individual increase of circulating vascular endothelial growth factor (VEGF) levels (r = 0.678, p = 0.015), even if mean VEGF levels were not modified by any training condition. Atrial natriuretic peptide (ANP) system components were not associated with increased ISIClamp during hypoxic training. CONCLUSIONS Physical training under hypoxic conditions could partially augment the favorable effects of exercise alone on myocellular insulin sensitivity in obese men with metabolic syndrome. Concomitant changes in VEGF might represent an underlying pathophysiological mechanism.
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A randomized control trial of the impact of LCPUFA-ω3 supplementation on body weight and insulin resistance in pubertal children with obesity.
López-Alarcón, M, Inda-Icaza, P, Márquez-Maldonado, MC, Armenta-Álvarez, A, Barbosa-Cortés, L, Maldonado-Hernández, J, Piña-Aguero, M, Barradas-Vázquez, A, Núñez-García, BA, Rodríguez-Cruz, M, et al
Pediatric obesity. 2019;(5):e12499
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Abstract
BACKGROUND Paediatric obesity and insulin resistance (IR) are potentially reversible inflammatory conditions. Long chain polyunsaturated fatty acids omega-3 (LCPUFA-ω3) show anti-inflammatory and metabolic properties, but their clinical efficacy is unclear. OBJECTIVE The objective of this study is to evaluate whether supplementation with LCPUFA-ω3 for 3 months reduces insulin resistance and weight to adolescents with obesity. METHODS Double-blind trial of 366 adolescents with obesity randomly assigned to 1.2-g LCPUFA-ω3 (DO3) or 1-g sunflower oil (DP) daily for 3 months; both groups received an energy-restricted diet. Children attended monthly for anthropometric, dietary, and clinical measurements. Basal and final blood samples were obtained to measure metabolic markers and erythrocytes fatty acids. Regression models were used for analysis. RESULTS A total of 119 DO3 and 126 DP children completed follow-up. At baseline, 92% of children presented IR, 66% hypertriglyceridemia, 37% low-grade inflammation, and 32% metabolic syndrome. Despite erythrocytes LCPUFA-ω3 increased more in DO3 (Median differences = 0.984 w/w%; 95 IC = 0.47, 1.53, P < 0.001), body weight, insulin, and HOMA changed similarly in both groups at the end of intervention. Adjusting for basal values, changes in weight, insulin, and HOMA was not related with supplementation. CONCLUSIONS Supplementation with LCPUFA-ω3 does not affect body weight or insulin in adolescents with obesity.
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TCF7L2-rs7903146 polymorphism modulates the effect of artichoke leaf extract supplementation on insulin resistance in metabolic syndrome: a randomized, double-blind, placebo-controlled trial.
Ebrahimi-Mameghani, M, Asghari-Jafarabadi, M, Rezazadeh, K
Journal of integrative medicine. 2018;(5):329-334
Abstract
BACKGROUND Transcription factor 7-like 2 (TCF7L2)-rs7903146 polymorphism is associated with increased risk of type 2 diabetes. The response of insulin and insulin resistance to artichoke leaf extract (ALE) may be affected by TCF7L2-rs7903146 polymorphism. OBJECTIVE This study examined the effects of ALE supplementation on metabolic parameters of the TCF7L2-rs7903146 polymorphism in patients with metabolic syndrome (MetS). DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS This double-blind clinical trial was conducted on 80 patients with MetS in Sina Clinic, Khoy, Iran. The patients were randomized into ALE or placebo groups to receive either ALE (1800 mg/d as four tablets) or matching placebo for 12 weeks. MAIN OUTCOME MEASURES Anthropometric indices, blood pressure, glucose and lipid profile levels were measured before and after the study. Moreover, patients were genotyped for TCF7L2 polymorphism. RESULTS ALE supplementation decreased insulin level and the homeostasis model assessment of insulin resistance (HOMA-IR) in patients with the TT genotype of TCF7L2-rs7903146 polymorphism (P < 0.05). There was no significant interaction between blood pressure, glucose and lipid profile response to ALE supplementation. CONCLUSION The responses of insulin and HOMA-IR to ALE supplementation have shown an interaction with single-nucleotide polymorphism rs7903146 in TCF7L2. TRIAL REGISTRATION Iranian Registry of Clinical Trial IRCT201409033320N9.
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The Effects of Flaxseed Oil Omega-3 Fatty Acids Supplementation on Metabolic Status of Patients with Polycystic Ovary Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial.
Mirmasoumi, G, Fazilati, M, Foroozanfard, F, Vahedpoor, Z, Mahmoodi, S, Taghizadeh, M, Esfeh, NK, Mohseni, M, Karbassizadeh, H, Asemi, Z
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2018;(4):222-228
Abstract
OBJECTIVE This study was conducted to evaluate the effects of flaxseed oil omega-3 fatty acids supplementation on metabolic status of patients with polycystic ovary syndrome (PCOS). METHODS This randomized double-blind, placebo-controlled trial was conducted on 60 women with PCOS according to the Rotterdam criteria aged 18-40 years old. Participants were randomly assigned into two groups to receive either 1,000 mg flaxseed oil omega-3 fatty acids (n=30) or placebo (n=30) twice a day for 12 weeks. Metabolic, endocrine, inflammatory factors were quantified at baseline and after the 12-week intervention. RESULTS After the 12-week intervention, compared to the placebo, flaxseed oil omega-3 supplementation significantly decreased insulin values (-2.6±7.7 vs.+1.3±3.9 µIU/mL, P=0.01), homeostasis model of assessment-estimated insulin resistance (-0.7±1.7 vs.+0.3±0.9, P=0.01), mF-G scores (-1.2±1.7 vs. -0.1±0.4, P=0.001), and increased quantitative insulin sensitivity check index (+0.01±0.02 vs. -0.01±0.02, P=0.01). In addition, supplementation with flaxseed oil omega-3 resulted in significant decreases in serum triglycerides (-5.1±20.9 vs.+9.7±26.1 mg/dL, P=0.01), VLDL-cholesterol (-1.0±4.2 vs.+1.9±5.2 mg/dL, P=0.01) and high-sensitivity C-reactive protein (hs-CRP) (-1.6±3.1 vs.+0.2±1.5 mg/L, P=0.004) compared to the placebo. We did not see any significant effect of flaxseed oil omega-3 supplementation on hormonal and other lipid profiles, and plasma nitric oxide levels. CONCLUSIONS Overall, flaxseed oil omega-3 supplementation for 12 weeks in women with PCOS had beneficial effects on insulin metabolism, mF-G scores, serum triglycerides, VLDL-cholesterol and hs-CRP levels, but did not affect hormonal and other lipid profiles, and plasma nitric oxide levels.
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Genistein supplementation improves insulin resistance and inflammatory state in non-alcoholic fatty liver patients: A randomized, controlled trial.
Amanat, S, Eftekhari, MH, Fararouei, M, Bagheri Lankarani, K, Massoumi, SJ
Clinical nutrition (Edinburgh, Scotland). 2018;(4):1210-1215
Abstract
BACKGROUND & AIMS The beneficial effect of genistein has indicated on metabolic disorders and inflammatory state. The aim of this study was to investigate the effect of genistein supplementation on non-alcoholic fatty liver disease (NAFLD) as the hepatic manifest of metabolic syndrome. METHODS In the present randomized double-blind controlled trial, patients with NAFLD were daily supplemented with either 250 mg genistein (n = 41) or placebo (n = 41) for 8-weeks. Both groups were instructed to follow an energy-balanced diet and physical activity recommendations. And their anthropometric and biochemical indices were assessed before and after the intervention. RESULTS At the end of the study, the genistein group had lower level of serum insulin (p = 0.001) and homeostasis model assessment for insulin resistance (HOMA-IR) (p = 0.041) compare to the placebo group. In addition serum malondialdehyde (MDA) (p = 0.004), tumor necrosis factor-α (TNF-α) (p = 0.045) and interleukin (IL)-6 (p = 0.018) also were lower in the genistein group. Compare with placebo, genistein supplementation significantly reduced waist to hip ratio (p = 0.021), body fat percentage (p = 0.015) and triglyceride (p = 0.018). However, there were no significant changes in BMI, fasting blood glucose (p = 0.122), alanine aminotransferase (ALT) (p = 0.536), aspartate aminotransferase (AST) (p = 0.265) between the two groups. CONCLUSIONS Oral supplementation with 250 mg genistein for 8-weeks can reduce insulin resistance, oxidative and inflammatory indices along with improvement in fat metabolism in patients with NAFLD. Studies with longer duration and larger samples might be needed to reveal other beneficial effects of genistein.
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Substituting poly- and mono-unsaturated fat for dietary carbohydrate reduces hyperinsulinemia in women with polycystic ovary syndrome.
Perelman, D, Coghlan, N, Lamendola, C, Carter, S, Abbasi, F, McLaughlin, T
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 2017;(4):324-327
Abstract
OBJECTIVE Hyperinsulinemia is a prevalent feature of polycystic ovary syndrome (PCOS), contributing to metabolic and reproductive manifestations of the syndrome. Weight loss reduces hyperinsulinemia but weight regain is the norm, thus preventing long-term benefits. In the absence of weight loss, replacement of dietary carbohydrate (CHO) with mono/polyunsaturated fat reduces ambient insulin concentrations in non-PCOS subjects. The current study evaluated whether this dietary intervention could ameliorate hyperinsulinemia in women with PCOS. DESIGN/SETTING/PATIENTS Obese women with PCOS (BMI 39 ± 7 kg/m2) and insulin resistance completed a crossover study (Stanford University Clinical Research Center) comparing two isocaloric diets, prepared by research dietitians, containing 60% CHO/25% fat versus 40% CHO/45% fat (both 15% protein and ≤7% saturated fat). After 3 weeks on each diet, daylong glucose, insulin, and fasting lipid/lipoproteins were measured. RESULTS Daylong glucose did not differ according to diet. Daylong insulin concentrations were substantially (30%) and significantly lower on the low CHO/higher fat diet. Beneficial changes in lipid profile were also observed. CONCLUSIONS Replacement of dietary CHO with mono/polyunsaturated fat yields clinically important reductions in daylong insulin concentrations, without adversely affecting lipid profile in obese, insulin-resistant women with PCOS. This simple and safe dietary intervention may constitute an important treatment for PCOS. ClinicalTrials.gov Identifier: NCT00186459.