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Serum metabolomics profiles in response to n-3 fatty acids in Chinese patients with type 2 diabetes: a double-blind randomised controlled trial.

ABSTRACT: We aimed to investigate the change of serum metabolomics in response to n-3 fatty acid supplements in Chinese patients with type 2 diabetes (T2D). In a double-blind parallel randomised controlled trial, 59 Chinese T2D patients were randomised to receive either fish oil (FO), flaxseed oil (FSO) or corn oil capsules (CO, served as a control group) and followed up for 180 days. An additional 17 healthy non-T2D participants were recruited at baseline for cross-sectional comparison between cases and non-cases. A total of 296 serum metabolites were measured among healthy controls and T2D patients before and after the intervention. Serum 3-carboxy-4-methyl-5-propyl-2-furanpropanoate (CMPF) (P-interaction?=?1.8?×?10(-7)) was the most significant metabolite identified by repeated-measures ANOVA, followed by eicosapentaenoate (P-interaction?=?4.6?×?10(-6)), 1-eicosapentaenoylglycerophosphocholine (P-interaction?=?3.4?×?10(-4)), docosahexaenoate (P-interaction?=?0.001), linolenate (n-3 or n-6, P-interaction?=?0.005) and docosapentaenoate (n-3, P-interaction?=?0.021). CMPF level was lower in T2D patients than in the healthy controls (P?=?0.014) and it was significantly increased in the FO compared with CO group (P?=?1.17?×?10(-7)). Furthermore, change of CMPF during the intervention was negatively correlated with change of serum triglycerides (P?=?0.016). In conclusion, furan fatty acid metabolite CMPF was the strongest biomarker of fish oil intake. The association of CMPF with metabolic markers warrants further investigation.

SUBMITTER: Zheng JS

PROVIDER: S-EPMC4941578 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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Serum metabolomics profiles in response to n-3 fatty acids in Chinese patients with type 2 diabetes: a double-blind randomised controlled trial.

Zheng Ju-Sheng JS Lin Mei M Imamura Fumiaki F Cai Wenwen W Wang Ling L Feng Jue-Ping JP Ruan Yue Y Tang Jun J Wang Fenglei F Yang Hong H Li Duo D

Scientific reports 20160712

We aimed to investigate the change of serum metabolomics in response to n-3 fatty acid supplements in Chinese patients with type 2 diabetes (T2D). In a double-blind parallel randomised controlled trial, 59 Chinese T2D patients were randomised to receive either fish oil (FO), flaxseed oil (FSO) or corn oil capsules (CO, served as a control group) and followed up for 180 days. An additional 17 healthy non-T2D participants were recruited at baseline for cross-sectional comparison between cases and ...[more]

PMID: 27404516

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Project description:Diabetes refers to a group of metabolic diseases with blood glucose of higher than normal ranges. Furthermore, n-3 polyunsaturated fatty acids are necessary for the regulation of the activity of human function. The effect of n-3 PUFA on diabetes has been investigated in animal studies, yet, the exact amount has not been set, to date. Irisin, as a new myokine, is released from skeletal muscle and Irisin levels decrease as a result of physical inactivity, overweightness, and obesity. Also, the reduction of serum irisin level is associated with development of insulin resistance and type 2 diabetes. This study was performed to assess the effects of n-3 PUFA supplementation on serum irisin level in patients with diabetes.This randomized clinical trial included 43 patients with type 2 diabetes (21 patients in the placebo group and 22 patients in the n-3 PUFA supplement group). They were randomized to groups, one receiving 10 weeks of either n-3 PUFA supplement and the other the placebo (1250 mg capsule, three times per day). Samples were also matched by age, gender, and body mass index (BMI) in the 2 groups. Anthropometric measurements, demographic information and dietary intakes were obtained both before and after the intervention. Serum irisin levels were measured before and after the intervention using human irisin enzyme linked immunosorbent assay (ELISA) kit. Independent t-test was used to compare the mean outcomes between groups.At baseline, irisin serum levels were not significantly different between the placebo and n-3 PUFA supplementation groups (P > 0.05). However, a significant change was observed between the groups after intervention (P = 0.04). Also there was a significant difference in mean change (after versus before the intervention) (P = 0.05). Compared to the placebo, n-3 PUFA supplementation decreased serum FBS and HbA1C (P = 0.036 and 0.001; respectively). Also, there were significant differences between changes of diastolic blood pressure and HOMA-IR after the intervention between the groups. The duration of illness was not considered as a confounding factor because there was no significant association between irisin level (after versus before the intervention) and the illness duration.The current study indicated that n-3 PUFA supplementation with a dosage of 1250 mg three times per day, resulted in increased serum irisin level of diabetic patients.

Project description:AIMS/HYPOTHESIS:The EFFECT-II study aimed to investigate the effects of dapagliflozin and omega-3 (n-3) carboxylic acids (OM-3CA), individually or combined, on liver fat content in individuals with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). METHODS:This randomised placebo-controlled double-blind parallel-group study was performed at five clinical research centres at university hospitals in Sweden. 84 participants with type 2 diabetes and NAFLD were randomly assigned 1:1:1:1 to four treatments by a centralised randomisation system, and all participants as well as investigators and staff involved in the study conduct and analyses were blinded to treatments. Each group received oral doses of one of the following: 10 mg dapagliflozin (n?=?21), 4 g OM-3CA (n?=?20), a combination of both (n?=?22) or placebo (n?=?21). The primary endpoint was liver fat content assessed by MRI (proton density fat fraction [PDFF]) and, in addition, total liver volume and markers of glucose and lipid metabolism as well as of hepatocyte injury and oxidative stress were assessed at baseline and after 12 weeks of treatment (completion of the trial). RESULTS:Participants had a mean age of 65.5 years (SD 5.9), BMI 31.2 kg/m2 (3.5) and liver PDFF 18% (9.3). All active treatments significantly reduced liver PDFF from baseline, relative changes: OM-3CA, -15%; dapagliflozin, -13%; OM-3CA + dapagliflozin, -21%. Only the combination treatment reduced liver PDFF (p?=?0.046) and total liver fat volume (relative change, -24%, p?= 0.037) in comparison with placebo. There was an interaction between the PNPLA3 I148M polymorphism and change in liver PDFF in the active treatment groups (p = 0.03). Dapagliflozin monotherapy, but not the combination with OM-3CA, reduced the levels of hepatocyte injury biomarkers, including alanine aminotransferase, aspartate aminotransferase, ?-glutamyl transferase (?-GT), cytokeratin (CK) 18-M30 and CK 18-M65 and plasma fibroblast growth factor 21 (FGF21). Changes in ?-GT correlated with changes in liver PDFF (? = 0.53, p?= 0.02). Dapagliflozin alone and in combination with OM-3CA improved glucose control and reduced body weight and abdominal fat volumes. Fatty acid oxidative stress biomarkers were not affected by treatments. There were no new or unexpected adverse events compared with previous studies with these treatments. CONCLUSIONS/INTERPRETATION:Combined treatment with dapagliflozin and OM-3CA significantly reduced liver fat content. Dapagliflozin monotherapy reduced all measured hepatocyte injury biomarkers and FGF21, suggesting a disease-modifying effect in NAFLD. TRIAL REGISTRATION:ClinicalTrials.gov NCT02279407 FUNDING: The study was funded by AstraZeneca.

Project description:INTRODUCTION:Psoriasis vulgaris is a common skin disease that is characterised by persistent localised erythematous scaly plaques. Yinxieling is a Chinese herbal formula for psoriasis that has been used for more than 20 years in China. To facilitate application, PSORI-CM01 was developed based on the optimisation and simplification of Yinxieling tablets performed in a previous study and in clinical practice. However, the scientific evidence regarding whether PSORI-CM01 is more effective for psoriasis than the original Yinxieling remains insufficient. Therefore, we designed a randomised clinical trial to investigate the effect, safety and cost-effectiveness of PSORI-CM01 granules compared with those of Yinxieling tablets for the treatment of patients with psoriasis. METHODS AND ANALYSIS:This ongoing study is a two-arm parallel, randomised, double-blind, double-dummy clinical trial. Five hundred and fifty-six participants with psoriasis will be recruited and then randomly allocated into two groups in a 1:1 ratio. Participants in PSORI-CM01 group will receive a 5.5?g granule of PSORI-CM01 two times daily and five placebo tablets three times daily for 12 weeks. The participants in the Yinxieling group will receive five Yinxieling tablets three times daily and a placebo granule two times daily for 12 weeks. The primary outcome is the reduction of the Psoriasis Area and Severity Index. The secondary outcomes include relapse rate, Visual Analogue Scale scores, body surface area and the Dermatology Life Quality Index. Cost-effectiveness analysis will be performed from a health and community care provider perspective. ETHICS AND DISSEMINATION:This research protocol had been reviewed and approved by the institutional review boards of three trial centres (Guangdong Provincial Hospital of Chinese Medicine (B2014-026-01), Affiliated Hospital of Tianjin Chinese Medicine Academy (2014-KY-001) and Third Hospital of Hangzhou (B2014-026-01)). The findings will be disseminated to the public through conference presentations and open-access journals. TRIAL REGISTRATION NUMBER:Chinese Clinical Trial Registry (ChiCTR-TRC-14005185); Pre-results.

Project description:While cardiovascular and mood benefits of dietary omega-3 fatty acids such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) are manifest, direct neurophysiological evidence of their effects on cortical activity is still limited. Hence we chose to examine the effects of two proprietary fish oil products with different EPA:DHA ratios (EPA-rich, high EPA:DHA; DHA-rich) on mental processing speed and visual evoked brain activity. We proposed that nonlinear multifocal visual evoked potentials (mfVEP) would be sensitive to any alteration of the neural function induced by omega-3 fatty acid supplementation, because the higher order kernel responses directly measure the degree of recovery of the neural system as a function of time following stimulation. Twenty-two healthy participants aged 18-34, with no known neurological or psychiatric disorder and not currently taking any nutritional supplementation, were recruited. A double-blind, crossover design was utilized, including a 30-day washout period, between two 30-day supplementation periods of the EPA-rich and DHA-rich diets (with order of diet randomized). Psychophysical choice reaction times and multi-focal nonlinear visual evoked potential (VEP) testing were performed at baseline (No Diet), and after each supplementation period. Following the EPA-rich supplementation, for stimulation at high luminance contrast, a significant reduction in the amplitude of the first slice of the second order VEP kernel response, previously related to activation in the magnocellular pathway, was observed. The correlations between the amplitude changes of short latency second and first order components were significantly different for the two supplementations. Significantly faster choice reaction times were observed psychophysically (compared with baseline performance) under the EPA-rich (but not DHA-rich) supplementation, while simple reaction times were not affected. The reduced nonlinearities observed under the EPA-rich diet suggest a mechanism involving more efficient neural recovery of magnocellular-like visual responses following cortical activation.

Project description:By far, no study has focused on observing the metabolomic profiles in perimenopause-related obesity. This study attempted to identify the metabolic characteristics of subjects with perimenopause obesity (PO). Thirty-nine perimenopausal Chinese women, 21 with PO and 18 without obesity (PN), were recruited in this study. A conventional ultra-high-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UHPLC-QTOF/MS) followed by principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used as untargeted metabolomics approaches to explore the serum metabolic profiles. Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst were used to identify the related metabolic pathways. A total of 46 differential metabolites, along with seven metabolic pathways relevant to PO were identified, which belonged to lipid, amino acids, carbohydrates, and organic acids. As for amino acids, we found a significant increase in l-arginine and d-ornithine in the positive ion (POS) mode and l-leucine, l-valine, l-tyrosine, and N-acetyl-l-tyrosine in the negative ion (NEG) mode and a significant decrease in l-proline in the POS mode of the PO group. We also found phosphatidylcholine (PC) (16:0/16:0), palmitic acid, and myristic acid, which are associated with the significant upregulation of lipid metabolism. Moreover, the serum indole lactic acid and indoleacetic acid were upregulated in the NEG mode. With respect to the metabolic pathways, the d-arginine and d-ornithine metabolisms and the arginine and proline metabolism pathways in POS mode were the most dominant PO-related pathways. The changes of metabolisms of lipid, amino acids, and indoleacetic acid provided a pathophysiological scenario for Chinese women with PO. We believe that the findings of this study are helpful for clinicians to take measures to prevent the women with PO from developing severe incurable obesity-related complications, such as cardiovascular disease and stroke.

Dataset Information

Serum metabolomics profiles in response to n-3 fatty acids in Chinese patients with type 2 diabetes: a double-blind randomised controlled trial.

Publications

Serum metabolomics profiles in response to n-3 fatty acids in Chinese patients with type 2 diabetes: a double-blind randomised controlled trial.

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