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A comparative study on indicators of vitamin A status and risk factors for sensitivity and specificity of the methods to detect vitamin A deficiency. 维生素A状态指标及危险因素对维生素A缺乏症检测方法敏感性和特异性的比较研究
IF 4.5 2区 医学 Q1 Medicine Pub Date : 2023-11-16 DOI: 10.1186/s12986-023-00768-7
Olivier O Sombié, Augustin N Zeba, Jérome W Somé, Adama Kazienga, Michael Grahn, Sherry A Tanumihardjo, Stefaan De Henauw, Souheila Abbeddou

Background: Serum retinol (SR) and retinol-binding protein (RBP) are commonly used indicators, but they are affected by infections and inflammation. This study aimed to assess the sensitivity and specificity of VA indicators to detect vitamin A deficiency (VAD) in 36-59-month-old children living in a rural area in Burkina Faso.

Methods: In a community-based study, two cross-sectional surveys were carried out from November 2016 to September 2017 in the health district of Dandé in Burkina Faso. The surveys included 115 children 36-59 months old. Indicators of VA and inflammation assessed in all children included SR, RBP and total liver VA reserves (TLR) estimated by retinol isotope dilution, and inflammation markers (C-reactive protein (CRP) and alpha 1-acid glycoprotein (AGP)). We calculated the sensitivity, specificity, positive and negative predictive values. In addition, the effects of inflammation, helminth infection, and season on sensitivity and specificity were assessed.

Results: The prevalence of VAD assessed by SR (< 0.7 µmol/L), RBP (< 0.7 µmol/L), and TLR (< 0.1 µmol/g liver) were, respectively, 30.9%, 33.3%, and 0%. Compared to TLR, the specificity, positive predictive value, and negative predictive value of SR were 71.1%, 0%, and 100%, and of RBP, were 68.9%, 0%, and 100%, respectively. The sensitivity was indeterminable for SR and RBP. The specificity of SR and RBP was lower during the dry season. Elevated CRP (> 5.0 mg/L) and AGP (> 1.0 g/L) were detected in 1.9% and 28.6% of children, respectively. The adjustment of VA indicators for inflammation improved SR's specificity to 75.9% and decreased RBP's specificity to 67.8%.

Conclusion: No cases of VAD were identified by TLR. However, (inflammation-adjusted) SR and RBP had varying accuracy in the estimation of VAD.

Trial registration: The study was registered, retrospectively, on 22 March 2018 as a clinical trial with the Pan African Clinical Trials Registry under the number Cochrane South Africa; PACTR201803002999356.

背景:血清视黄醇(SR)和视黄醇结合蛋白(RBP)是常用的指标,但受感染和炎症的影响。本研究旨在评估VA指标在布基纳法索农村地区36-59个月儿童中检测维生素A缺乏症(VAD)的敏感性和特异性。方法:以社区为基础,于2016年11月至2017年9月在布基纳法索dand卫生区进行了两次横断面调查。调查对象包括115名年龄在36-59个月之间的儿童。所有患儿的VA和炎症指标包括:视黄醇同位素稀释法估计的SR、RBP和总肝脏VA储备(TLR),以及炎症标志物(c反应蛋白(CRP)和α 1-酸性糖蛋白(AGP))。计算敏感性、特异性、阳性预测值和阴性预测值。此外,还评估了炎症、寄生虫感染和季节对敏感性和特异性的影响。结果:以SR (5.0 mg/L)和AGP (> 1.0 g/L)评估的VAD患病率分别为1.9%和28.6%。调整VA炎症指标后,SR特异性提高至75.9%,RBP特异性降低至67.8%。结论:TLR未发现VAD病例。然而,(炎症调整)SR和RBP在VAD估计中的准确性不同。试验注册:该研究于2018年3月22日作为临床试验在泛非临床试验注册中心回顾性注册,编号为Cochrane South Africa;PACTR201803002999356。
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引用次数: 0
Early adulthood weight change, midlife "Life's essential 8" health status and risk of cardiometabolic diseases: a chinese nationwide cohort study. 成年早期体重变化、中年“生命必需8”健康状况和心脏代谢疾病风险:一项中国全国性队列研究。
IF 4.5 2区 医学 Q1 Medicine Pub Date : 2023-11-01 DOI: 10.1186/s12986-023-00765-w
Qiuyu Cao, Mian Li, Guijun Qin, Li Yan, Jiang He, Min Xu, Yu Xu, Tiange Wang, Yuhong Chen, Shuangyuan Wang, Hong Lin, Zhiyun Zhao, Zhengnan Gao, Tianshu Zeng, Ruying Hu, Xuefeng Yu, Gang Chen, Qing Su, Yiming Mu, Lulu Chen, Xulei Tang, Qin Wan, Guixia Wang, Feixia Shen, Zuojie Luo, Yingfen Qin, Li Chen, Yanan Huo, Qiang Li, Zhen Ye, Yinfei Zhang, Chao Liu, Youmin Wang, Shengli Wu, Tao Yang, Huacong Deng, Jiajun Zhao, Lixin Shi, Guang Ning, Weiqing Wang, Jieli Lu, Yufang Bi

Background: The association between weight change during early adulthood and cardiometabolic diseases remains uncertain in Chinese population. Whether the association varies with comprehensive cardiovascular health (CVH) in midlife assessed by "Life's Essential 8" has not been characterized. We aim to examine the associations of early adulthood weight change and midlife "Life's Essential 8" CVH status with cardiometabolic outcomes in a Chinese cohort.

Methods: The study participants were from the China Cardiometabolic Disease and Cancer Cohort (4 C) Study. This analysis included 72,610 middle-aged and older participants followed for a median of 3.6 years. At baseline, the participants recalled body weight at age 20 and 40 years, and we calculated change in weight and BMI between 20 and 40 years of age. Health behaviors information in "Life's Essential 8" was collected by questionnaire, and health factors were measured in the study center. During follow-up, we ascertained incident cardiovascular events based on medical records, and diagnosed incident diabetes according to the American Diabetes Association 2010 criteria.

Results: 72,610 study participants were included with a mean age of 56.0 ± 8.8 years and 29% of them were males. Weight gain of more than 10 kg between 20 and 40 years of age was associated with 22% increased risk of incident cardiovascular events (HR: 1.22; 95%CI: 1.04-1.43) and 38% increased risk of diabetes (HR: 1.38; 95%CI: 1.25-1.53) compared to stable weight. Besides, the association of weight gain more than 10 kg in early adulthood with cardiometabolic risk was even stronger in those with low CVH score in midlife (HR: 2.44; 95%CI: 2.01-2.97 for incident cardiovascular events; HR: 2.20; 95%CI: 1.90-2.55 for incident diabetes) or with few ideal cardiovascular health metrics in midlife.

Conclusions: Our study indicated that weight gain in early adulthood was associated with significantly increased risk of cardiometabolic diseases. And the association could be stronger in those with poor CVH profiles in midlife. These findings confirmed the significance of weight management during early adulthood and suggested that individuals who experienced substantial weight gain in early life should be encouraged to maintain good CVH status in Chinese population.

背景:在中国人群中,成年早期体重变化与心脏代谢疾病之间的关系尚不确定。这种关联是否与“生命的基本8”评估的中年综合心血管健康(CVH)有关,目前尚未确定。我们的目的是在一个中国队列中研究成年早期体重变化和中年“生命必需8”CVH状态与心脏代谢结果的关系。方法:研究参与者来自中国心脏代谢疾病和癌症队列(4C)研究。该分析包括72610名中老年参与者,平均随访3.6年。在基线时,参与者回忆了20岁和40岁时的体重,我们计算了20岁到40岁之间体重和BMI的变化。采用问卷调查的方法收集《生活必需品8》中的健康行为信息,并在研究中心对健康因素进行测量。在随访期间,我们根据医疗记录确定了心血管事件,并根据美国糖尿病协会2010年的标准诊断为糖尿病。结果:72610名研究参与者,平均年龄56.0岁 ± 8.8岁,其中男性占29%。与稳定体重相比,20至40岁期间体重增加超过10公斤与心血管事件风险增加22%(HR:1.22;95%CI:1.04-1.43)和糖尿病风险增加38%(HR:1.38;95%CI:1.25-1.53)相关。此外,在中年CVH评分较低的人群中,成年早期体重增加超过10公斤与心脏代谢风险的相关性更强(HR:2.44;95%CI:2.01-2.97,针对心血管事件;HR:2.20;95%CI:1.90-2.55,针对糖尿病事件),或中年时几乎没有理想的心血管健康指标。结论:我们的研究表明,成年早期的体重增加与心脏代谢疾病的风险显著增加有关。在中年CVH状况不佳的人群中,这种联系可能会更强。这些发现证实了成年早期体重管理的重要性,并建议应鼓励早期体重大幅增加的人在中国人群中保持良好的CVH状态。
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引用次数: 0
Healthy lifestyle scores associate with incidence of type 2 diabetes mediated by uric acid. 健康生活方式评分与尿酸介导的2型糖尿病的发病率相关。
IF 4.5 2区 医学 Q1 Medicine Pub Date : 2023-11-01 DOI: 10.1186/s12986-023-00763-y
Xinyue He, Wei Shao, Senhai Yu, Jiazhou Yu, Changzhen Huang, Haiqing Ren, Chengguo Liu, Yuying Xu, Yimin Zhu

Background: Whether and to what extent serum uric acid (SUA) mediates the association between combined lifestyle behaviors and type 2 diabetes mellitus (T2DM) remain unclear. This study aimed to investigate the role of SUA in the relationship between healthy lifestyle scores (HLS) and the incidence of T2DM.

Methods: This prospective study used data from Zhejiang Metabolic Syndrome cohort. A HLS (5-point scale including healthy waist circumference (WC), never smoking, high physical activity, healthy diet and moderate alcohol intake) was estimated in 13,919 participants, who had SUA at baseline examination in 2009-2014, and were followed-up to 2021-2022 to ascertain incident of T2DM. Cox proportional hazards models and mediation analysis were used to examine the associations between HLS, SUA and T2DM.

Results: We included 13,919 participants aged 18 years or older without diabetes at baseline (mean age 54.6 [SD 13.9] years, 58.7% female). During a median follow-up of 9.94 years, 645 cases of T2DM occurred. Compared with participants with a poor HLS, those with 4-5 low-risk lifestyle factors showed a 60% reduction in the risk of developing T2DM (adjusted HR, 0.40; 95% CI: 0.28-0.57). Further, the population-attributable risk percent (95% CI) of T2DM for poor adherence to the overall healthy lifestyle (< 4 low-risk factors) was 43.24% (30.02%, 56.46%). The HLS was inversely associated with SUA level. With per score increased in HLS, the beta (95% CI) of SUA (log transformed) was - 0.03 (- 0.03, - 0.02), and the odds ratio (95% CI) of hyperuricemia was 0.82 (0.77, 0.86). The relationship between the HLS and risk of T2DM was mediated by SUA with a 13.06% mediation effect. There was no significant combined effect of HLS and SUA on risk of T2DM (P = 0.097).

Conclusions: The relationship between overall healthy lifestyle behaviors and T2DM was reconfirmed and the association appeared to be mediated by SUA. The mediation effect of baseline SUA was more pronounced among women who were below 60 years old.

背景:血清尿酸(SUA)是否以及在多大程度上介导综合生活方式行为与2型糖尿病(T2DM)之间的关系尚不清楚。本研究旨在探讨SUA在健康生活方式评分(HLS)与T2DM发病率之间的关系中的作用。方法:本前瞻性研究使用了浙江代谢综合征队列的数据。对13919名参与者进行了HLS(5分量表,包括健康腰围(WC)、从不吸烟、高体力活动、健康饮食和适度饮酒)评估,这些参与者在2009-2014年的基线检查中患有SUA,并随访至2021-2022年,以确定T2DM的发生率。Cox比例风险模型和中介分析用于检验HLS、SUA和T2DM之间的相关性。结果:我们纳入了13919名18岁或18岁以上基线时没有糖尿病的参与者(平均年龄54.6[SD13.9]岁,58.7%为女性)。在9.94年的中位随访中,发生了645例T2DM。与HLS较差的参与者相比,那些有4-5种低风险生活方式因素的参与者患T2DM的风险降低了60%(调整后的HR为0.40;95%CI:0.28-0.57)。此外,2型糖尿病患者对整体健康生活方式依从性差的人群归因风险百分比(95%CI)(结论:总体健康生活方式行为与2型糖尿病之间的关系得到了重新确认,这种关系似乎是由SUA介导的。基线SUA的介导作用在60岁以下的女性中更为明显。
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引用次数: 0
The association of serum betaine concentrations with the risk of new-onset cancers: results from two independent nested case-control studies. 血清甜菜碱浓度与新发癌症风险的相关性:两项独立的嵌套病例对照研究结果。
IF 4.5 2区 医学 Q1 Medicine Pub Date : 2023-10-30 DOI: 10.1186/s12986-023-00755-y
Hailun Xie, Kangping Zhang, Yaping Wei, Guotian Ruan, Heyang Zhang, Shuqun Li, Yun Song, Ping Chen, Lishun Liu, Binyan Wang, Hanping Shi

Evidence from epidemiologic studies on the association of circulating betaine levels with the incident risk of cancer has been inconsistent. We aimed to investigate the prospective association of serum betaine concentrations with the risk of cancer. We performed two, nested, case-control studies utilizing data from the "H-type Hypertension Prevention and Control Public Service Project" (HHPCP) and the China Stroke Primary Prevention Trial (CSPPT), with 2782 participants (1391 cancer cases and 1391 matched controls) in the discovery cohort, and 228 participants (114 cancer cases and 114 matched controls) in the validation cohort. Odds ratios (OR) of the association between betaine and cancer were calculated using conditional logistic regression models. There was an association between serum betaine as a continuous variable and total cancer (OR = 1.03, 95%CI = 0.99-1.07, p = 0.097). Among cancer subtypes, a positive association was found between serum betaine and the risk of lung cancer, and an inverse association was found with other cancers. Interestingly, a U-shaped association was observed between serum betaine and digestive cancers, with a turning point of 5.01 mmol/L for betaine (betaine < 5.01 mmol/L, OR = 0.82, 95%CI = 0.59-1.14, p = 0.228; betaine ≥ 5.01 mmol/L, OR = 1.08, 95%CI = 1.01-1.17, p = 0.036). In the validation cohort, a significant association between serum betaine as a continuous variable and total cancer (OR = 1.48, 95%CI = 1.06-2.05, P = 0.020) was also found. High serum betaine was associated with increased risk of total cancer and lung cancer, and a U-shaped association was found with the risk of digestive cancers, with a turning point at about 5.01 mmol/L.

关于循环甜菜碱水平与癌症发病风险之间关系的流行病学研究证据不一致。我们旨在研究血清甜菜碱浓度与癌症风险的前瞻性关联。我们利用“H型高血压预防和控制公共服务项目”(HHPCP)和中国卒中一级预防试验(CSPT)的数据进行了两项嵌套的病例对照研究,发现队列中有2782名参与者(1391例癌症病例和1391例匹配对照),验证队列中有228名参与者(114例癌症病例和114例配对对照)。用条件逻辑回归模型计算甜菜碱和癌症之间的比值比(OR)。血清甜菜碱作为一个连续变量与癌症总数之间存在相关性(OR = 1.03,95%CI = 0.99-1.07,p = 在癌症亚型中,发现血清甜菜碱与癌症风险呈正相关,而与其他癌症呈负相关。有趣的是,在血清甜菜碱和消化道癌症之间观察到U型关联,甜菜碱的转折点为5.01 mmol/L(甜菜碱
{"title":"The association of serum betaine concentrations with the risk of new-onset cancers: results from two independent nested case-control studies.","authors":"Hailun Xie,&nbsp;Kangping Zhang,&nbsp;Yaping Wei,&nbsp;Guotian Ruan,&nbsp;Heyang Zhang,&nbsp;Shuqun Li,&nbsp;Yun Song,&nbsp;Ping Chen,&nbsp;Lishun Liu,&nbsp;Binyan Wang,&nbsp;Hanping Shi","doi":"10.1186/s12986-023-00755-y","DOIUrl":"10.1186/s12986-023-00755-y","url":null,"abstract":"<p><p>Evidence from epidemiologic studies on the association of circulating betaine levels with the incident risk of cancer has been inconsistent. We aimed to investigate the prospective association of serum betaine concentrations with the risk of cancer. We performed two, nested, case-control studies utilizing data from the \"H-type Hypertension Prevention and Control Public Service Project\" (HHPCP) and the China Stroke Primary Prevention Trial (CSPPT), with 2782 participants (1391 cancer cases and 1391 matched controls) in the discovery cohort, and 228 participants (114 cancer cases and 114 matched controls) in the validation cohort. Odds ratios (OR) of the association between betaine and cancer were calculated using conditional logistic regression models. There was an association between serum betaine as a continuous variable and total cancer (OR = 1.03, 95%CI = 0.99-1.07, p = 0.097). Among cancer subtypes, a positive association was found between serum betaine and the risk of lung cancer, and an inverse association was found with other cancers. Interestingly, a U-shaped association was observed between serum betaine and digestive cancers, with a turning point of 5.01 mmol/L for betaine (betaine < 5.01 mmol/L, OR = 0.82, 95%CI = 0.59-1.14, p = 0.228; betaine ≥ 5.01 mmol/L, OR = 1.08, 95%CI = 1.01-1.17, p = 0.036). In the validation cohort, a significant association between serum betaine as a continuous variable and total cancer (OR = 1.48, 95%CI = 1.06-2.05, P = 0.020) was also found. High serum betaine was associated with increased risk of total cancer and lung cancer, and a U-shaped association was found with the risk of digestive cancers, with a turning point at about 5.01 mmol/L.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10614375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71413297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Does dietary nitrate boost the effects of caloric restriction on brain health? Potential physiological mechanisms and implications for future research. 饮食中的硝酸盐是否能促进热量限制对大脑健康的影响?潜在的生理机制和对未来研究的启示。
IF 4.5 2区 医学 Q1 Medicine Pub Date : 2023-10-25 DOI: 10.1186/s12986-023-00766-9
Mushari Alharbi, Blossom Cm Stephan, Oliver M Shannon, Mario Siervo

Dementia is a highly prevalent and costly disease characterised by deterioration of cognitive and physical capacity due to changes in brain function and structure. Given the absence of effective treatment options for dementia, dietary and other lifestyle approaches have been advocated as potential strategies to reduce the burden of this condition. Maintaining an optimal nutritional status is vital for the preservation of brain function and structure. Several studies have recognised the significant role of nutritional factors to protect and enhance metabolic, cerebrovascular, and neurocognitive functions. Caloric restriction (CR) positively impacts on brain function via a modulation of mitochondrial efficiency, endothelial function, neuro-inflammatory, antioxidant and autophagy responses. Dietary nitrate, which serves as a substrate for the ubiquitous gasotransmitter nitric oxide (NO), has been identified as a promising nutritional intervention that could have an important role in improving vascular and metabolic brain regulation by affecting oxidative metabolism, ROS production, and endothelial and neuronal integrity. Only one study has recently tested the combined effects of both interventions and showed preliminary, positive outcomes cognitive function. This paper explores the potential synergistic effects of a nutritional strategy based on the co-administration of CR and a high-nitrate diet as a potential and more effective (than either intervention alone) strategy to protect brain health and reduce dementia risk.

痴呆症是一种高度流行且代价高昂的疾病,其特征是由于大脑功能和结构的变化而导致认知和身体能力下降。鉴于痴呆症缺乏有效的治疗选择,饮食和其他生活方式方法被认为是减轻这种疾病负担的潜在策略。保持最佳的营养状态对保持大脑功能和结构至关重要。一些研究已经认识到营养因素在保护和增强代谢、脑血管和神经认知功能方面的重要作用。热量限制(CR)通过调节线粒体效率、内皮功能、神经炎症、抗氧化和自噬反应对大脑功能产生积极影响。膳食硝酸盐是普遍存在的气体传输型一氧化氮(NO)的底物,已被确定为一种有前途的营养干预措施,通过影响氧化代谢、ROS产生以及内皮和神经元完整性,在改善血管和代谢性大脑调节方面发挥重要作用。最近只有一项研究测试了这两种干预措施的综合效果,并显示出初步的、积极的结果——认知功能。本文探讨了基于CR和高硝酸盐饮食联合给药的营养策略的潜在协同效应,作为一种潜在且更有效(比单独干预更有效)的策略来保护大脑健康和降低痴呆风险。
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引用次数: 0
Differential effects of plant-based flours on metabolic homeostasis and the gut microbiota in high-fat fed rats. 植物性面粉对高脂肪喂养大鼠代谢稳态和肠道微生物群的不同影响。
IF 4.5 2区 医学 Q1 Medicine Pub Date : 2023-10-19 DOI: 10.1186/s12986-023-00767-8
Taylor M Martinez, Hallie R Wachsmuth, Rachel K Meyer, Savanna N Weninger, Adelina I Lane, Archana Kangath, Gabriele Schiro, Daniel Laubitz, Jennifer H Stern, Frank A Duca

Background: The gut microbiome is a salient contributor to the development of obesity, and diet is the greatest modifier of the gut microbiome, which highlights the need to better understand how specific diets alter the gut microbiota to impact metabolic disease. Increased dietary fiber intake shifts the gut microbiome and improves energy and glucose homeostasis. Dietary fibers are found in various plant-based flours which vary in fiber composition. However, the comparative efficacy of specific plant-based flours to improve energy homeostasis and the mechanism by which this occurs is not well characterized.

Methods: In experiment 1, obese rats were fed a high fat diet (HFD) supplemented with four different plant-based flours for 12 weeks. Barley flour (BF), oat bran (OB), wheat bran (WB), and Hi-maize amylose (HMA) were incorporated into the HFD at 5% or 10% total fiber content and were compared to a HFD control. For experiment 2, lean, chow-fed rats were switched to HFD supplemented with 10% WB or BF to determine the preventative efficacy of flour supplementation.

Results: In experiment 1, 10% BF and 10% WB reduced body weight and adiposity gain and increased cecal butyrate. Gut microbiota analysis of WB and BF treated rats revealed increases in relative abundance of SCFA-producing bacteria. 10% WB and BF were also efficacious in preventing HFD-induced obesity; 10% WB and BF decreased body weight and adiposity, improved glucose tolerance, and reduced inflammatory markers and lipogenic enzyme expression in liver and adipose tissue. These effects were accompanied by alterations in the gut microbiota including increased relative abundance of Lactobacillus and LachnospiraceaeUCG001, along with increased portal taurodeoxycholic acid (TDCA) in 10% WB and BF rats compared to HFD rats.

Conclusions: Therapeutic and preventative supplementation with 10%, but not 5%, WB or BF improves metabolic homeostasis, which is possibly due to gut microbiome-induced alterations. Specifically, these effects are proposed to be due to increased concentrations of intestinal butyrate and circulating TDCA.

背景:肠道微生物组是肥胖发展的重要因素,而饮食是肠道微生物组的最大调节剂,这突出表明需要更好地了解特定饮食如何改变肠道微生物组以影响代谢性疾病。膳食纤维摄入量的增加改变了肠道微生物组,改善了能量和葡萄糖稳态。膳食纤维存在于各种不同纤维组成的植物性面粉中。然而,特定植物性面粉改善能量稳态的比较功效及其发生机制尚未得到很好的表征。方法:在实验1中,给肥胖大鼠喂食添加四种不同植物性面粉的高脂肪饮食(HFD)12周。将大麦粉(BF)、燕麦麸(OB)、小麦麸(WB)和高玉米直链淀粉(HMA)以5%或10%的总纤维含量掺入HFD中,并与HFD对照进行比较。对于实验2,将瘦的、食物喂养的大鼠切换到补充有10%WB或BF的HFD,以确定补充面粉的预防效果。结果:在实验1中,10%BF和10%WB降低了体重和肥胖增加,并增加了盲肠丁酸盐。WB和BF处理大鼠的肠道微生物群分析显示,SCFA产生菌的相对丰度增加。10%WB和BF在预防HFD诱导的肥胖方面也是有效的;10%WB和BF降低了体重和肥胖,改善了葡萄糖耐量,并降低了肝脏和脂肪组织中的炎症标志物和脂肪生成酶的表达。这些影响伴随着肠道微生物群的改变,包括与HFD大鼠相比,10%WB和BF大鼠的乳酸杆菌和钩端螺旋杆菌UCG001的相对丰度增加,以及门脉牛脱氧胆酸(TDCA)增加。结论:治疗性和预防性补充10%而非5%的WB或BF可以改善代谢稳态,这可能是由于肠道微生物组诱导的改变。具体而言,这些影响被认为是由于肠道丁酸盐和循环TDCA的浓度增加。
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引用次数: 0
New insights into the nutritional genomics of adult-onset riboflavin-responsive diseases. 成人发病核黄素反应性疾病营养基因组学的新见解。
IF 4.5 2区 医学 Q1 Medicine Pub Date : 2023-10-16 DOI: 10.1186/s12986-023-00764-x
Chiara Murgia, Ankush Dehlia, Mark A Guthridge

Riboflavin, or vitamin B2, is an essential nutrient that serves as a precursor to flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN). The binding of the FAD and/or FMN cofactors to flavoproteins is critical for regulating their assembly and activity. There are over 90 proteins in the human flavoproteome that regulate a diverse array of biochemical pathways including mitochondrial metabolism, riboflavin transport, ubiquinone and FAD synthesis, antioxidant signalling, one-carbon metabolism, nitric oxide signalling and peroxisome oxidative metabolism. The identification of patients with genetic variants in flavoprotein genes that lead to adult-onset pathologies remains a major diagnostic challenge. However, once identified, many patients with adult-onset inborn errors of metabolism demonstrate remarkable responses to riboflavin therapy. We review the structure:function relationships of mutant flavoproteins and propose new mechanistic insights into adult-onset riboflavin-responsive pathologies and metabolic dysregulations that apply to multiple biochemical pathways. We further address the vexing issue of how the inheritance of genetic variants in flavoprotein genes leads to an adult-onset disease with complex symptomologies and varying severities. We also propose a broad clinical framework that may not only improve the current diagnostic rates, but also facilitate a personalized approach to riboflavin therapy that is low cost, safe and lead to transformative outcomes in many patients.

核黄素或维生素B2是一种必需营养素,是黄素腺嘌呤二核苷酸(FAD)和黄素单核苷酸(FMN)的前体。FAD和/或FMN辅因子与黄素蛋白的结合对于调节其组装和活性至关重要。人类黄素蛋白质组中有90多种蛋白质调节多种生化途径,包括线粒体代谢、核黄素转运、泛醌和FAD合成、抗氧化信号传导、单碳代谢、一氧化氮信号传导和过氧化物酶体氧化代谢。识别具有导致成人发病的黄蛋白基因遗传变异的患者仍然是一个主要的诊断挑战。然而,一旦发现,许多成年先天性代谢错误患者对核黄素治疗表现出显著的反应。我们综述了突变黄素蛋白的结构-功能关系,并对成人发病的核黄素反应性病理和代谢失调提出了新的机制见解,这些病理和代谢紊乱适用于多种生物化学途径。我们进一步解决了一个令人烦恼的问题,即黄蛋白基因的遗传变异如何导致一种具有复杂症状和不同严重程度的成人发病。我们还提出了一个广泛的临床框架,该框架不仅可以提高当前的诊断率,还可以促进核黄素治疗的个性化方法,该方法成本低、安全,并在许多患者中带来变革性的结果。
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引用次数: 0
The effect of the modified fat-protein unit algorithm compared with that of carbohydrate counting on postprandial glucose in adults with type-1 diabetes when consuming meals with differing macronutrient compositions: a randomized crossover trial. 1型糖尿病成年人在食用不同宏量营养成分的膳食时,改良脂肪-蛋白质单位算法与碳水化合物计数对餐后血糖的影响的比较:一项随机交叉试验。
IF 4.5 2区 医学 Q1 Medicine Pub Date : 2023-10-16 DOI: 10.1186/s12986-023-00757-w
Yunying Cai, Mengge Li, Lun Zhang, Jie Zhang, Heng Su

Background: The optimization of glucose control in type-1 diabetes is challenged by postprandial glycemic variability. This study aimed to compare the postprandial glycemic effects of carbohydrate counting and the modified fat-protein unit (FPU) algorithms following meals with different protein and fat emphases in adults with type-1 diabetes.

Methods: Thirty adults with type-1 diabetes aged 18 to 45 years participated in a randomized crossover trial. In a random order, participants consumed four test meals with equivalent energy and different macronutrient emphases on four separate mornings. The modified FPU algorithms and carbohydrate counting were used to determine the insulin dose for the test meals. A continuous glucose monitoring system was used to measured postprandial glycemia.

Results: Compared with carbohydrate counting, the modified FPU algorithm significantly decreased the late postprandial mean glucose levels (p = 0.026) in high protein-fat meals. The number of hypoglycemia episodes was similar between insulin dosing algorithms for the high protein-fat meals; hypoglycemic events were considerably higher for the modified FPU in the normal protein-fat meal (p = 0.042).

Conclusions: The modified FPU algorithm may improve postprandial glycemic control after consuming high protein-fat meals in adults with type-1 diabetes but may result in increased hypoglycemia risk when used with a normal protein-fat meal.

背景:1型糖尿病血糖控制的优化受到餐后血糖变化的挑战。本研究旨在比较1型糖尿病成年人在不同蛋白质和脂肪重点饮食后碳水化合物计数和改良脂肪-蛋白质单位(FPU)算法对餐后血糖的影响。方法:30名18至45岁的1型糖尿病成年人参加了一项随机交叉试验。按照随机顺序,参与者在四个不同的早晨吃了四顿能量相等、重点不同的测试餐。使用改良的FPU算法和碳水化合物计数来确定测试膳食的胰岛素剂量。使用连续血糖监测系统来测量餐后血糖。结果:与碳水化合物计数相比,改进的FPU算法显著降低了餐后后期的平均血糖水平(p = 0.026)。高蛋白脂肪餐的胰岛素给药算法之间的低血糖发作次数相似;在正常蛋白质-脂肪膳食中,改良FPU的低血糖事件明显更高(p = 0.042)。结论:改良的FPU算法可以改善1型糖尿病成年人在食用高蛋白脂肪餐后的餐后血糖控制,但与正常蛋白脂肪餐一起使用可能会增加低血糖风险。
{"title":"The effect of the modified fat-protein unit algorithm compared with that of carbohydrate counting on postprandial glucose in adults with type-1 diabetes when consuming meals with differing macronutrient compositions: a randomized crossover trial.","authors":"Yunying Cai, Mengge Li, Lun Zhang, Jie Zhang, Heng Su","doi":"10.1186/s12986-023-00757-w","DOIUrl":"10.1186/s12986-023-00757-w","url":null,"abstract":"<p><strong>Background: </strong>The optimization of glucose control in type-1 diabetes is challenged by postprandial glycemic variability. This study aimed to compare the postprandial glycemic effects of carbohydrate counting and the modified fat-protein unit (FPU) algorithms following meals with different protein and fat emphases in adults with type-1 diabetes.</p><p><strong>Methods: </strong>Thirty adults with type-1 diabetes aged 18 to 45 years participated in a randomized crossover trial. In a random order, participants consumed four test meals with equivalent energy and different macronutrient emphases on four separate mornings. The modified FPU algorithms and carbohydrate counting were used to determine the insulin dose for the test meals. A continuous glucose monitoring system was used to measured postprandial glycemia.</p><p><strong>Results: </strong>Compared with carbohydrate counting, the modified FPU algorithm significantly decreased the late postprandial mean glucose levels (p = 0.026) in high protein-fat meals. The number of hypoglycemia episodes was similar between insulin dosing algorithms for the high protein-fat meals; hypoglycemic events were considerably higher for the modified FPU in the normal protein-fat meal (p = 0.042).</p><p><strong>Conclusions: </strong>The modified FPU algorithm may improve postprandial glycemic control after consuming high protein-fat meals in adults with type-1 diabetes but may result in increased hypoglycemia risk when used with a normal protein-fat meal.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10580506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41237150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Prospective association between an obesogenic dietary pattern in early adolescence and metabolomics derived and traditional cardiometabolic risk scores in adolescents and young adults from the ALSPAC cohort. 青少年早期致胖饮食模式与ALSPAC队列中青少年和年轻人的代谢组学衍生和传统心脏代谢风险评分之间的前瞻性关联
IF 4.5 2区 医学 Q1 Medicine Pub Date : 2023-09-15 DOI: 10.1186/s12986-023-00754-z
Eduard Martínez Solsona, Laura Johnson, Kate Northstone, Genevieve Buckland

Background: Dietary intake during early life may be a modifying factor for cardiometabolic risk (CMR). Metabolomic profiling may enable more precise identification of CMR in adolescence than traditional CMR scores. We aim to assess and compare the prospective associations between an obesogenic dietary pattern (DP) score at age 13 years with a novel vs. traditional CMR score in adolescence and young adulthood in the Avon Longitudinal Study of Parents and Children (ALSPAC).

Methods: Study participants were ALSPAC children with diet diary data at age 13. The obesogenic DP z-score, characterized by high energy-density, high % of energy from total fat and free sugars, and low fibre density, was previously derived using reduced rank regression. CMR scores were calculated by combining novel metabolites or traditional risk factors (fat mass index, insulin resistance, mean arterial blood pressure, triacylglycerol, HDL and LDL cholesterol) at age 15 (n = 1808), 17 (n = 1629), and 24 years (n = 1760). Multivariable linear regression models estimated associations of DP z-score with log-transformed CMR z-scores.

Results: Compared to the lowest tertile, the highest DP z-score tertile at age 13 was associated with an increase in the metabolomics CMR z-score at age 15 (β = 0.20, 95% CI 0.09, 0.32, p trend < 0.001) and at age 17 (β = 0.22, 95% CI 0.10, 0.34, p trend < 0.001), and with the traditional CMR z-score at age 15 (β = 0.15, 95% CI 0.05, 0.24, p trend 0.020). There was no evidence of an association at age 17 for the traditional CMR z-score (β = 0.07, 95% CI -0.03, 0.16, p trend 0.137) or for both scores at age 24.

Conclusions: An obesogenic DP was associated with greater CMR in adolescents. Stronger associations were observed with a novel metabolite CMR score compared to traditional risk factors. There may be benefits from modifying diet during adolescence for CMR health, which should be prioritized for further research in trials.

背景:生命早期的饮食摄入可能是心血管代谢风险(CMR)的一个调节因素。代谢组学分析可以比传统的CMR评分更准确地识别青少年的CMR。我们的目的是评估和比较13岁时的致肥性饮食模式(DP)评分与青少年和青年期的新型CMR评分与传统CMR评分之间的前瞻性关联。方法:研究对象为13岁时有饮食日记资料的ALSPAC儿童。致肥性DP z-score的特征是高能量密度,总脂肪和游离糖的能量百分比高,纤维密度低,先前使用降秩回归得出。CMR评分是通过结合15岁(n = 1808)、17岁(n = 1629)和24岁(n = 1760)时的新代谢物或传统危险因素(脂肪质量指数、胰岛素抵抗、平均动脉血压、甘油三酯、高密度脂蛋白和低密度脂蛋白胆固醇)来计算的。多变量线性回归模型估计DP z-score与log-transform CMR z-score的关联。结果:与最低分位数相比,13岁时DP z评分最高的分位数与15岁时代谢组学CMR z评分的增加相关(β = 0.20, 95% CI 0.09, 0.32, p趋势)。结论:肥胖性DP与青少年较高的CMR相关。与传统的危险因素相比,新的代谢物CMR评分观察到更强的相关性。在青春期调整饮食可能对CMR健康有好处,这应该优先用于进一步的试验研究。
{"title":"Prospective association between an obesogenic dietary pattern in early adolescence and metabolomics derived and traditional cardiometabolic risk scores in adolescents and young adults from the ALSPAC cohort.","authors":"Eduard Martínez Solsona, Laura Johnson, Kate Northstone, Genevieve Buckland","doi":"10.1186/s12986-023-00754-z","DOIUrl":"10.1186/s12986-023-00754-z","url":null,"abstract":"<p><strong>Background: </strong>Dietary intake during early life may be a modifying factor for cardiometabolic risk (CMR). Metabolomic profiling may enable more precise identification of CMR in adolescence than traditional CMR scores. We aim to assess and compare the prospective associations between an obesogenic dietary pattern (DP) score at age 13 years with a novel vs. traditional CMR score in adolescence and young adulthood in the Avon Longitudinal Study of Parents and Children (ALSPAC).</p><p><strong>Methods: </strong>Study participants were ALSPAC children with diet diary data at age 13. The obesogenic DP z-score, characterized by high energy-density, high % of energy from total fat and free sugars, and low fibre density, was previously derived using reduced rank regression. CMR scores were calculated by combining novel metabolites or traditional risk factors (fat mass index, insulin resistance, mean arterial blood pressure, triacylglycerol, HDL and LDL cholesterol) at age 15 (n = 1808), 17 (n = 1629), and 24 years (n = 1760). Multivariable linear regression models estimated associations of DP z-score with log-transformed CMR z-scores.</p><p><strong>Results: </strong>Compared to the lowest tertile, the highest DP z-score tertile at age 13 was associated with an increase in the metabolomics CMR z-score at age 15 (β = 0.20, 95% CI 0.09, 0.32, p trend < 0.001) and at age 17 (β = 0.22, 95% CI 0.10, 0.34, p trend < 0.001), and with the traditional CMR z-score at age 15 (β = 0.15, 95% CI 0.05, 0.24, p trend 0.020). There was no evidence of an association at age 17 for the traditional CMR z-score (β = 0.07, 95% CI -0.03, 0.16, p trend 0.137) or for both scores at age 24.</p><p><strong>Conclusions: </strong>An obesogenic DP was associated with greater CMR in adolescents. Stronger associations were observed with a novel metabolite CMR score compared to traditional risk factors. There may be benefits from modifying diet during adolescence for CMR health, which should be prioritized for further research in trials.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10504726/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10310479","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
METTL3 exacerbates insulin resistance in hepatocytes by regulating m6A modification of cytochrome P450 2B6. METTL3通过调节m6A修饰细胞色素P450 2B6而加剧肝细胞的胰岛素抵抗。
IF 4.5 2区 医学 Q1 Medicine Pub Date : 2023-09-15 DOI: 10.1186/s12986-023-00762-z
Yongqing Li, Dantong Zhang, Yinan Gao, Peijun Wang, Zejun Wang, Bingyang Zhang, Junjun Liu, Diwen Ye, Wanshan Ma, Sumei Lu

Background: Insulin resistance (IR) in hepatocytes endangers human health, and frequently results in the development of non-alcoholic fatty liver disease (NAFLD). Research on m6A methylation of RNA molecules has gained popularity in recent years; however, the molecular mechanisms regulating the processes of m6A modification and IR are not known. The cytochrome P450 (CYP450) enzyme system, which is mainly found in the liver, is associated with the pathogenesis of NAFLD. However, few studies have been conducted on CYP450 related m6A methylation. Here, we investigated the role of the methyltransferase METTL3 in exacerbating IR in hepatocytes, mainly focusing on the regulation of m6A modifications in CYP2B6.

Methods and results: Analysis using dot blot and epitranscriptomic chips revealed that the m6A modification pattern of the transcriptome in high-fat diet (HFD)-induced fatty liver and free fatty acid (FFA)-induced fatty hepatocytes showed significant changes. CYP450 family members, especially Cyp2b10, whose homolog in humans is CYP2B6, led to a noticeable increase in m6A levels in HFD-induced mice livers. Application of the METTL3 methyltransferase inhibitor, STM2457, increased the level of insulin sensitivity in hepatocytes. We then analyzed the role of METTL3 in regulating m6A modification of CYP2B6 in hepatocytes. METTL3 regulated the m6A modification of CYP2B6, and a positive correlation was found between the levels of CYP2B6 translation and m6A modifications. Furthermore, interference with METTL3 expression and exposure to STM2457 inhibited METTL3 activity, which in turn interfered with the phosphorylated insulin receptor substrate (pIRS)-glucose transporter 2 (GLUT2) insulin signaling pathway; overexpression of CYP2B6 hindered IRS phosphorylation and translocation of GLUT2 to membranes, which ultimately exacerbated IR.

Conclusion: These findings offer unique insights into the role that METTL3-mediated m6A modifications of CYP2B6 play in regulating insulin sensitivity in hepatocytes and provide key information for the development of strategies to induce m6A modifications for the clinical treatment of NAFLD.

背景:肝细胞胰岛素抵抗(IR)危害人体健康,并经常导致非酒精性脂肪性肝病(NAFLD)的发展。近年来,对RNA分子m6A甲基化的研究得到了广泛的关注;然而,调控m6A修饰和IR过程的分子机制尚不清楚。主要存在于肝脏的细胞色素P450 (CYP450)酶系统与NAFLD的发病机制有关。然而,关于CYP450相关的m6A甲基化的研究很少。在这里,我们研究了甲基转移酶METTL3在加剧肝细胞IR中的作用,主要关注CYP2B6中m6A修饰的调节。方法与结果:采用dot blot和表转录组芯片分析发现,高脂饮食(HFD)诱导的脂肪肝和游离脂肪酸(FFA)诱导的脂肪肝细胞中转录组的m6A修饰模式发生了显著变化。CYP450家族成员,特别是Cyp2b10,其在人类中的同源物是CYP2B6,导致hfd诱导小鼠肝脏中m6A水平显著升高。METTL3甲基转移酶抑制剂STM2457的应用增加了肝细胞的胰岛素敏感性水平。然后,我们分析了METTL3在调节肝细胞中CYP2B6的m6A修饰中的作用。METTL3调控CYP2B6的m6A修饰,CYP2B6翻译水平与m6A修饰水平呈正相关。此外,干扰METTL3表达和暴露于STM2457会抑制METTL3活性,从而干扰磷酸化的胰岛素受体底物(pIRS)-葡萄糖转运蛋白2 (GLUT2)胰岛素信号通路;CYP2B6的过表达阻碍了IRS磷酸化和GLUT2向膜的易位,最终加重了IR。结论:这些发现为mettl3介导的CYP2B6的m6A修饰在调节肝细胞胰岛素敏感性中的作用提供了独特的见解,并为制定诱导m6A修饰的策略以用于NAFLD的临床治疗提供了关键信息。
{"title":"METTL3 exacerbates insulin resistance in hepatocytes by regulating m<sup>6</sup>A modification of cytochrome P450 2B6.","authors":"Yongqing Li, Dantong Zhang, Yinan Gao, Peijun Wang, Zejun Wang, Bingyang Zhang, Junjun Liu, Diwen Ye, Wanshan Ma, Sumei Lu","doi":"10.1186/s12986-023-00762-z","DOIUrl":"10.1186/s12986-023-00762-z","url":null,"abstract":"<p><strong>Background: </strong>Insulin resistance (IR) in hepatocytes endangers human health, and frequently results in the development of non-alcoholic fatty liver disease (NAFLD). Research on m<sup>6</sup>A methylation of RNA molecules has gained popularity in recent years; however, the molecular mechanisms regulating the processes of m<sup>6</sup>A modification and IR are not known. The cytochrome P450 (CYP450) enzyme system, which is mainly found in the liver, is associated with the pathogenesis of NAFLD. However, few studies have been conducted on CYP450 related m<sup>6</sup>A methylation. Here, we investigated the role of the methyltransferase METTL3 in exacerbating IR in hepatocytes, mainly focusing on the regulation of m<sup>6</sup>A modifications in CYP2B6.</p><p><strong>Methods and results: </strong>Analysis using dot blot and epitranscriptomic chips revealed that the m<sup>6</sup>A modification pattern of the transcriptome in high-fat diet (HFD)-induced fatty liver and free fatty acid (FFA)-induced fatty hepatocytes showed significant changes. CYP450 family members, especially Cyp2b10, whose homolog in humans is CYP2B6, led to a noticeable increase in m<sup>6</sup>A levels in HFD-induced mice livers. Application of the METTL3 methyltransferase inhibitor, STM2457, increased the level of insulin sensitivity in hepatocytes. We then analyzed the role of METTL3 in regulating m<sup>6</sup>A modification of CYP2B6 in hepatocytes. METTL3 regulated the m<sup>6</sup>A modification of CYP2B6, and a positive correlation was found between the levels of CYP2B6 translation and m<sup>6</sup>A modifications. Furthermore, interference with METTL3 expression and exposure to STM2457 inhibited METTL3 activity, which in turn interfered with the phosphorylated insulin receptor substrate (pIRS)-glucose transporter 2 (GLUT2) insulin signaling pathway; overexpression of CYP2B6 hindered IRS phosphorylation and translocation of GLUT2 to membranes, which ultimately exacerbated IR.</p><p><strong>Conclusion: </strong>These findings offer unique insights into the role that METTL3-mediated m<sup>6</sup>A modifications of CYP2B6 play in regulating insulin sensitivity in hepatocytes and provide key information for the development of strategies to induce m<sup>6</sup>A modifications for the clinical treatment of NAFLD.</p>","PeriodicalId":19196,"journal":{"name":"Nutrition & Metabolism","volume":null,"pages":null},"PeriodicalIF":4.5,"publicationDate":"2023-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10502999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10260138","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 1
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