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Multilevel analysis of individual heterogeneity and discriminatory accuracy (MAIHDA) to understand how obesity risk varies according to multiple lifestyle behavior recommendations. 个体异质性和歧视性准确性(MAIHDA)的多水平分析,以了解肥胖风险如何根据多种生活方式行为建议而变化。
IF 3.8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-07 DOI: 10.1038/s41366-025-02010-1
Ansuman Swain, Natalie Pearson, Scott A Willis, William Johnson

Background: The combined and interactive effects of multiple lifestyle behaviours on obesity risk are not well understood. We used Multilevel Analysis of Individual Heterogeneity and Discriminatory Accuracy (MAIHDA) to examine how adherence to public health recommendations for five lifestyle behaviours affects BMI and obesity risk.

Methods: The sample included 139,540 men and 125,455 women from the UK Biobank. We categorized fruit and vegetable intake, physical activity, sleep duration and alcohol intake as binary variables (meeting vs. not meeting guidelines), and smoking status into three categories (previous, current, never). These categories were combined to form 48 unique strata, representing all possible combinations of the five behaviours. Linear and binary logistic MAIHDA models were used, with individuals nested within strata, and BMI and obesity status (obesity vs. normal weight) as outcomes. Three models were employed: Model 1 (null), Model 2 (with fixed effects for lifestyle behaviours), and Model 3 (with confounders and fixed effects). Variance Partition Coefficient (VPC), Proportional Change in Variance (PCV), and predicted BMI and obesity risk were estimated.

Results: For both sexes, strata with the lowest obesity risk were associated with meeting most recommendations, while strata with the highest risk were linked to meeting few. Logistic Model 1 VPCs revealed 7% of variance in obesity risk among males and 5% among females was explained by between-strata differences. In Model 3, VPCs attenuated to 0.5% among males and 0.1% among females, suggesting differences in obesity risk were largely additive effects. PCVs from Model 3 also indicated primarily additive rather than interactive effects. Results were similar for BMI in the linear models.

Conclusions: Using a novel statistical approach, this study shows that additive effects of multiple lifestyle behaviours predominantly explain differences in BMI and obesity risk. Meeting more public health lifestyle recommendations is important in mitigating obesity risk.

背景:多种生活方式行为对肥胖风险的综合和相互作用尚不清楚。我们使用个体异质性和歧视性准确性的多水平分析(MAIHDA)来检验五种生活方式行为的公共卫生建议如何影响BMI和肥胖风险。方法:样本包括来自英国生物银行的139,540名男性和125,455名女性。我们将水果和蔬菜摄入量、体力活动、睡眠时间和酒精摄入量作为二元变量(符合与不符合指南),并将吸烟状况分为三类(以前、现在、从不)。这些类别组合形成48个独特的地层,代表了五种行为的所有可能组合。使用线性和二元逻辑MAIHDA模型,将个体嵌套在地层中,并将BMI和肥胖状态(肥胖与正常体重)作为结果。我们采用了三个模型:模型1 (null)、模型2(对生活方式行为具有固定效应)和模型3(具有混杂因素和固定效应)。评估方差划分系数(VPC)、方差比例变化(PCV)和预测BMI和肥胖风险。结果:对于两性而言,肥胖风险最低的阶层符合大多数建议,而肥胖风险最高的阶层则很少符合建议。Logistic模型1 VPCs显示,男性肥胖风险变异的7%和女性肥胖风险变异的5%是由阶层间差异解释的。在模型3中,男性和女性的VPCs分别减弱至0.5%和0.1%,表明肥胖风险的差异在很大程度上是加性效应。Model 3的pcv也显示出主要的叠加效应,而非交互效应。线性模型的BMI结果相似。结论:本研究采用一种新颖的统计方法,表明多种生活方式行为的叠加效应主要解释了BMI和肥胖风险的差异。满足更多的公共健康生活方式建议对于减轻肥胖风险很重要。
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引用次数: 0
Greater early postprandial GLP-1 increase after Roux-en-Y than one-anastomosis gastric bypass, with unchanged secretin: a randomized controlled trial. 一项随机对照试验:Roux-en-Y术后早期餐后GLP-1升高高于一次胃旁路吻合,且分泌素不变。
IF 3.8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-06 DOI: 10.1038/s41366-025-02000-3
S Heinonen, J E Karppinen, T Saarinen, P-H Groop, A Juuti, J J Holst, K H Pietiläinen

Background: Few studies have compared gut hormone responses between bariatric procedures. This study compared Roux-en-Y and one-anastomosis gastric bypass (RYGB and OAGB) regarding glucagon-like peptide-1 (GLP-1), secretin, and glucose-insulin dynamics.

Methods: This study included 41 participants (RYGB: n = 21, OAGB: n = 20) from the randomized RYSA trial with similar amounts of bypassed intestine between the procedures. Plasma GLP-1, secretin, glucose, insulin, and C-peptide were measured during a 360-min mixed-meal test before, and at 6- and 12-months after surgery. Outcomes included total and early-phase (0-60 min) areas under the curve (AUCs) and peak concentrations. Visual analogue scales were used to measure hunger and satiety.

Results: Both procedures resulted in ~25% weight loss and marked metabolic improvements over 12 months. While fasting GLP-1 remained largely unchanged, postprandial concentrations rose markedly at 6 months (total AUC increase in RYGB: ~330%, OAGB: ~259%; p < 0.001) and remained elevated at 12 months. The increases in early-phase GLP-1 AUC were 31% higher in RYGB than OAGB at 6 months (95% CI: 3 to 68; p = 0.030) and 25% higher at 12 months (95% CI: -2 to 59; p = 0.072). Peak GLP-1 increases were significantly higher ( ~ 32%) after RYGB at both follow-ups (p < 0.05). Postprandial reduction in hunger was greater after RYGB than OAGB from baseline to 12 months. Fasting or postprandial secretin concentrations showed no significant changes. Both operations were associated with decreased fasting glucose, insulin, and C-peptide; increased early glucose but decreased glucose total AUCs; and increased insulin early AUC and C-peptide total and early AUCs. Glucose early-phase AUC and peak concentration increases were greater after RYGB than OAGB.

Conclusions: Both RYGB and OAGB lead to markedly enhanced postprandial GLP-1 responses, with no corresponding change in secretin levels. RYGB produces higher early postprandial increases in GLP-1 and glucose than OAGB, demonstrating that procedural differences can influence gut hormone and glucose responses.

背景:很少有研究比较减肥手术之间的肠道激素反应。本研究比较了Roux-en-Y和单吻合式胃旁路术(RYGB和OAGB)在胰高血糖素样肽-1 (GLP-1)、分泌素和葡萄糖-胰岛素动力学方面的差异。方法:本研究包括41名随机RYSA试验的参与者(RYGB: n = 21, OAGB: n = 20),在手术之间有相似数量的旁路肠。术前、术后6个月和12个月分别进行360分钟混合餐试验,测定血浆GLP-1、分泌素、葡萄糖、胰岛素和c肽。结果包括总和早期(0-60 min)曲线下面积(auc)和峰值浓度。视觉模拟量表用于测量饥饿和饱腹感。结果:在12个月的时间里,这两种方法都使体重减轻了25%,并显著改善了代谢。虽然空腹GLP-1基本保持不变,但餐后浓度在6个月时明显升高(RYGB的总AUC增加约330%,OAGB的总AUC增加约259%;p结论:RYGB和OAGB均可显著增强餐后GLP-1反应,而分泌素水平无相应变化。RYGB比OAGB在餐后早期产生更高的GLP-1和葡萄糖升高,表明程序差异可以影响肠道激素和葡萄糖反应。
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引用次数: 0
The effect of obesity and aging on NAD+/Sirtuin metabolism transcription and DNA methylation in subcutaneous adipose tissue of monozygotic twin pairs discordant for BMI. 肥胖和衰老对同卵双胞胎皮下脂肪组织NAD+/Sirtuin代谢转录和DNA甲基化的影响与BMI不一致
IF 3.8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-05 DOI: 10.1038/s41366-025-02007-w
Helena A K Lapatto, Birgitta W van der Kolk, Maheswary Muniandy, Sini Heinonen, Aino Heikkinen, Marcus Alvarez, Seung Hyuk T Lee, Riikka Jokinen, Jesper Lundbom, Juho Kuula, Antti Hakkarainen, Per-Henrik Groop, Jaakko Kaprio, Taru Tukiainen, Miina Ollikainen, Päivi Pajukanta, Eija Pirinen, Kirsi H Pietiläinen

Introduction: The expression and/or activity of sirtuins (SIRTs), nicotinamide adenine dinucleotide (NAD+)-dependent enzymes that regulate cellular energy metabolism, is decreased in obesity and in aging in animal models. However, the impact of obesity compared to aging on NAD+/SIRT expression in human white adipose tissue (AT) remains unexplored. Here, we unravel the effects of obesity and aging on the expression of NAD+/SIRT pathway and their associated genes in subcutaneous AT of identical twin pairs discordant for weight, in two age groups.

Methods: We examined 49 monozygotic twin pairs discordant for BMI (within-pair difference in BMI ≥ 2.5 kg/m2, with mean BMIs 25.6 kg/m2 (leaner) and 30.8 kg/m2 (heavier), aged 22-38 and 56-69 years. Detailed phenotyping included body composition, insulin resistance (oral glucose tolerance test) and plasma lipids and inflammation markers. RNA sequencing and DNA methylation analyses in AT identified differentially expressed and methylated NAD+/SIRT pathway genes in obesity and aging, with linear mixed models linking gene expression to metabolic features.

Results: SIRT5 and NAD+ biosynthetic genes were downregulated in AT in both obesity and aging. Obesity was characterized by downregulation of AT NAD+/SIRT genes, and NAD+/SIRT regulated mitochondrial oxidative metabolism genes, and upregulation of stress markers. Aging showed a downregulation of AT PARPs, except upregulation for PARP1, a main consumer of NAD+. Mitochondrial metabolism and glycolysis genes were linked to corresponding DNA methylation. Downregulation of NAD+/SIRT genes correlated with increased adiposity, insulin resistance, inflammation, and dyslipidemia.

Conclusion: Impaired NAD+/SIRT metabolism in AT may play a key role in obesity- and aging-related diseases. Both conditions are characterized by downregulation of NAD+/SIRT pathway genes, correlating with increased adiposity, insulin resistance, inflammation, and dyslipidemia. Obesity uniquely disrupts expression of NAD+/SIRT regulated mitochondrial genes, while aging is characterized by altered PARP expression, particularly increased PARP1, likely exacerbating metabolic dysfunction in AT.

在动物模型中,调节细胞能量代谢的烟酰胺腺嘌呤二核苷酸(NAD+)依赖性酶sirtuins (SIRTs)的表达和/或活性在肥胖和衰老中降低。然而,与衰老相比,肥胖对人类白色脂肪组织(AT)中NAD+/SIRT表达的影响尚不清楚。在这里,我们揭示了肥胖和衰老对两个年龄组体重不一致的同卵双胞胎皮下AT中NAD+/SIRT通路及其相关基因表达的影响。方法:选取年龄22 ~ 38岁和56 ~ 69岁的49对BMI不一致的同卵双胞胎(BMI≥2.5 kg/m2的对内差异,平均BMI为25.6 kg/m2(较瘦)和30.8 kg/m2(较重))。详细的表型包括身体组成、胰岛素抵抗(口服葡萄糖耐量试验)、血浆脂质和炎症标志物。AT的RNA测序和DNA甲基化分析发现了肥胖和衰老中NAD+/SIRT通路基因的差异表达和甲基化,并将基因表达与代谢特征联系起来。结果:肥胖和衰老AT中SIRT5和NAD+生物合成基因均下调。肥胖的特征是AT NAD+/SIRT基因下调,NAD+/SIRT调控线粒体氧化代谢基因,应激标志物上调。除了NAD+的主要消耗者PARP1上调外,衰老表现出AT PARPs下调。线粒体代谢和糖酵解基因与相应的DNA甲基化有关。NAD+/SIRT基因下调与肥胖、胰岛素抵抗、炎症和血脂异常增加相关。结论:AT中NAD+/SIRT代谢受损可能在肥胖和衰老相关疾病中起关键作用。这两种情况都以NAD+/SIRT通路基因下调为特征,与肥胖、胰岛素抵抗、炎症和血脂异常增加相关。肥胖独特地破坏了NAD+/SIRT调节的线粒体基因的表达,而衰老的特征是PARP表达的改变,特别是PARP1的增加,可能加剧了AT的代谢功能障碍。
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引用次数: 0
Mental health outcomes in obesity interventions with GLP-1 receptor agonists: is it similar to other obesity interventions? A narrative review with systematic evidence synthesis. GLP-1受体激动剂干预肥胖的心理健康结果:与其他肥胖干预相似吗?有系统证据综合的叙述性评论。
IF 3.8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-05 DOI: 10.1038/s41366-025-02002-1
Darin Osborne, Elamin Abdelgadir

Obesity is a chronic, debilitating condition with complex biological, psychosocial, and behavioral underpinnings. While the cardiometabolic consequences are reasonably well-established, the often-forgotten bidirectional association between obesity and mental health disorders, including anxiety, eating disorders, depression, and even suicidal ideations, is rarely assessed as a primary endpoint in obesity intervention studies. Similarly, documents summarizing and comparing various types of obesity interventions and their effects of mental health in this rapidly evolving field are scarce. This narrative review synthesizes the evidence on the psychological impact of lifestyle, pharmacological, and surgical interventions in the treatment of obesity. Special focus is placed on glucagon-like peptide-1 (GLP-1) receptor agonists, given their rising global use and emerging concerns regarding mental health safety. A thorough literature review was conducted across the MEDLINE, Embase, and Cochrane databases, focusing on meta-analyses, systematic reviews, and clinical trials published up to June 2025. Studies examining psychological outcomes in patients undergoing lifestyle modifications, pharmacotherapy, or bariatric surgery for weight loss were included. Mental health domains considered included quality of life, anxiety, depression, and suicidality. Due to the vast array of obesity interventions and the broad nature of mental health in the literature, this review was conducted to provide a narrative summary. Behavioral interventions consistently showed no harm to mental health and demonstrated modest improvements in depression and mental health-related quality of life. Bariatric surgery was associated with short-to-medium-term reductions in depressive and anxiety symptoms, though long-term benefits were attenuated, with some studies reporting increased suicidality after five years. Pharmacotherapies, including orlistat, bupropion/naltrexone, and phentermine/topiramate, showed mixed psychiatric impacts. The GLP-1 receptor agonists (Semaglutide, liraglutide, Tirzepatide) have shown an improvement in patient-reported mental wellbeing in several trials. Concerningly, pharmacovigilance data initially suggested a possible link with suicidality; however, subsequent robust cohort studies and meta-analyses have refuted this association. Mental health is a critical yet underprioritized element of obesity management. The current evidence suggests that most weight loss interventions are psychologically safe or beneficial, but long-term data remain limited, particularly for GLP-1 receptor agonists. Future randomized trials must incorporate mental health as a prespecified outcome, and individualized treatment approaches should integrate psychological support to optimize long-term outcomes. This review has summarized, side-by-side, the various outcomes of obesity interventions on mental health.

肥胖是一种慢性衰弱疾病,具有复杂的生物、社会心理和行为基础。虽然对心脏代谢的影响已经相当明确,但肥胖与心理健康障碍(包括焦虑、饮食失调、抑郁甚至自杀意念)之间的双向关联却经常被遗忘,很少被评估为肥胖干预研究的主要终点。同样,在这个快速发展的领域中,总结和比较各种肥胖干预措施及其对心理健康影响的文献很少。这篇叙述性综述综合了生活方式、药物和手术干预治疗肥胖的心理影响的证据。特别关注胰高血糖素样肽-1 (GLP-1)受体激动剂,鉴于其全球使用的增加和对精神健康安全的新关注。对MEDLINE、Embase和Cochrane数据库进行了全面的文献综述,重点关注截至2025年6月发表的荟萃分析、系统综述和临床试验。研究包括对接受生活方式改变、药物治疗或减肥手术的患者的心理结果的研究。考虑的心理健康领域包括生活质量、焦虑、抑郁和自杀。由于文献中大量的肥胖干预措施和心理健康的广泛性质,本综述旨在提供一个叙述性的总结。行为干预始终显示对心理健康没有危害,并且在抑郁症和与心理健康相关的生活质量方面表现出适度的改善。减肥手术与抑郁和焦虑症状的中短期减轻有关,尽管长期益处减弱,一些研究报告五年后自杀率增加。药物治疗,包括奥利司他、安非他酮/纳曲酮和芬特明/托吡酯,显示出混合的精神影响。GLP-1受体激动剂(Semaglutide, liraglutide, tizepatide)在几项试验中显示出对患者报告的精神健康的改善。令人关注的是,药物警戒数据最初表明可能与自杀有关;然而,随后强有力的队列研究和荟萃分析驳斥了这种关联。心理健康是肥胖管理中一个关键但未得到重视的因素。目前的证据表明,大多数减肥干预措施在心理上是安全的或有益的,但长期数据仍然有限,特别是GLP-1受体激动剂。未来的随机试验必须将心理健康作为预先指定的结果,个性化的治疗方法应该结合心理支持来优化长期结果。这篇综述并排总结了肥胖干预对心理健康的各种结果。
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引用次数: 0
Sex-specific longitudinal associations between repeatedly measured movement behaviours and adiposity measures in school-aged children: a compositional data analysis approach. 学龄儿童反复测量运动行为与肥胖测量之间的性别纵向关联:一种成分数据分析方法。
IF 3.8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-05 DOI: 10.1038/s41366-025-01969-1
Natarajan Padmapriya, Suresh Anand Sadananthan, Navin Michael, Mya-Thway Tint, Sarah Yi Xuan Tan, Airu Chia, Yeshe Manuel Kway, Shirong Cai, Jia Ying Toh, Kok Hian Tan, Yap Seng Chong, Yung Seng Lee, Fabian Yap, Mary F-F Chong, Keith M Godfrey, Johan G Eriksson, Jonathan Y Bernard, S Sendhil Velan, Falk Müller-Riemenschneider

Background: Movement behaviours, including moderate-to-vigorous-intensity physical activity (MVPA), light-intensity physical activity (LPA), sedentary behaviour (SB), and sleep, influence childhood adiposity. However, their collective impact on adiposity from a sex-specific perspective remains underexplored. Our research examined the sex-specific longitudinal associations of 24-h movement behaviours with body mass index (BMI) and abdominal adiposity among children.

Methods: In the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort study, we repeatedly measured 24-h movement behaviours using wrist-worn accelerometers (ActiGraph GT3x) and assessed adiposity (BMI, abdominal circumference, and MRI-based abdominal fat volumes) at three time points (ages 5.5-6, 7.5-8, and 10-10.5 years) within the same children in a longitudinal design. Compositional multivariable linear mixed-effect modelling and isotemporal substitution were used to estimate the associations.

Results: 531 children (49.5% girls) were included in the analysis. Significant interactions between movement behaviours and sex were observed across all outcomes. In girls, higher MVPA relative to other behaviours was linked to lower BMI [-0.8 (-1.5, -0.1) kg/m²] and total abdominal adiposity [-225.5 (-451.6, -2.5) mL], while in boys, longer sleep duration was associated with lower BMI [-1.6 (-3.2, -0.1) kg/m²] and total abdominal adiposity [-624.2 (-1225.6, -31.3) mL]. The isotemporal substitution model showed that replacing 30 min of LPA/SB with MVPA reduced BMI and abdominal circumference by 1-2% and MRI-measured abdominal adiposity by 6-9% in both sexes. However, replacing LPA/SB with sleep reduced BMI and abdominal circumference by 1% and MRI-measured adiposity by 3-6% only in boys, with no changes in girls. These associations were pronounced on visceral adiposity.

Conclusion: This study highlights sex-specific associations of movement behaviours with adiposity in school-aged children, with stronger associations observed in MRI-derived measures compared to conventional adiposity indices. Replacing LPA/SB with MVPA reduced BMI and abdominal adiposity in both sexes, with particularly pronounced effects on visceral adiposity. However, sleep replacement benefits were observed only in boys, suggesting the need for gender-sensitive approaches in lifestyle interventions.

背景:运动行为,包括中高强度身体活动(MVPA)、低强度身体活动(LPA)、久坐行为(SB)和睡眠,都会影响儿童肥胖。然而,从性别角度来看,它们对肥胖的共同影响仍未得到充分探讨。我们的研究考察了儿童24小时运动行为与体重指数(BMI)和腹部肥胖之间的性别纵向关联。方法:在新加坡成长迈向健康结局(GUSTO)队列研究中,我们使用腕带加速度计(ActiGraph GT3x)重复测量24小时运动行为,并在纵向设计中评估同一儿童的三个时间点(5.5-6岁、7.5-8岁和10-10.5岁)的肥胖(BMI、腹围和基于mri的腹部脂肪体积)。使用组合多变量线性混合效应模型和等时间替代来估计关联。结果:531名儿童(女孩49.5%)被纳入分析。在所有结果中都观察到运动行为和性别之间的显著相互作用。在女孩中,较高的MVPA相对于其他行为与较低的BMI [-0.8 (-1.5, -0.1) kg/m²]和腹部总脂肪[-225.5 (-451.6,-2.5)mL]有关,而在男孩中,较长的睡眠时间与较低的BMI [-1.6 (-3.2, -0.1) kg/m²]和腹部总脂肪[-624.2 (-1225.6,-31.3)mL]有关。等颞期替代模型显示,用MVPA代替30分钟的LPA/SB可使男女体重指数和腹围降低1-2%,mri测量的腹部脂肪减少6-9%。然而,用睡眠代替LPA/SB,仅男孩的BMI和腹围降低了1%,mri测量的肥胖减少了3-6%,女孩没有变化。这些关联在内脏肥胖上很明显。结论:这项研究强调了运动行为与学龄期儿童肥胖之间的性别特异性关联,与传统的肥胖指数相比,mri衍生的测量结果显示了更强的关联。用MVPA代替LPA/SB降低了两性的BMI和腹部脂肪,对内脏脂肪的影响尤其显著。然而,只有在男孩身上观察到睡眠替代的好处,这表明在生活方式干预中需要对性别敏感的方法。
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引用次数: 0
Distinct fasting and postprandial bile acid responses following Roux-en-Y and one-anastomosis gastric bypass. Roux-en-Y和单吻合术胃旁路术后不同的空腹和餐后胆汁酸反应。
IF 3.8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-05 DOI: 10.1038/s41366-025-01999-9
Matti Jänis, Tuure Saarinen, Jari E Karppinen, Per-Henrik Groop, Mikko Neuvonen, Mikko Niemi, Anne Juuti, Kirsi H Pietiläinen, Sini Heinonen

Objective: Bariatric surgery is the most effective long-term treatment for obesity, but how different surgical techniques affect metabolic outcomes remains unclear. Bile acids (BAs), increasingly recognized as metabolic regulators, rise postprandially after surgery and may mediate some of these effects. This exploratory study investigates the differential impact of Roux-en-Y gastric bypass (RYGB) and one-anastomosis gastric bypass (OAGB) on BA profiles and associated metabolic outcomes over one year.

Methods: Forty-five patients with obesity (15 men, 30 women; mean (SD) age 46.6 (7.1) years) were randomized to receive either RYGB (n = 24) or OAGB (n = 20). Clinical assessments, body composition measurements (Dual energy X-ray absorptiometer), fasting blood tests including lipids and inflammation markers, 360-minute mixed meal test, and oral glucose tolerance test were conducted 4-6 weeks before and at 6 and 12 months after operation. Plasma total and 15 individual BAs (LC-MS) were measured at eight time points during the mixed meal test.

Results: RYGB led to an increase in postprandial secondary BAs from baseline to 12 months (p = 0.004), particularly deoxycholic acid (DCA; p < 0.001) and glycodeoxycholic acid (GDCA; p = 0.006) compared with OAGB. In contrast, OAGB led to an increase in postprandial primary taurine-conjugated BAs (p = 0.039), especially taurochenodeoxycholic acid (TCDCA; p = 0.036) compared with RYGB. Similarly, RYGB increased unconjugated secondary BAs, especially DCA, whereas OAGB increased conjugated primary BAs, like TCA and GCA during fasting. Metabolic improvements were similar in both groups. Post-RYGB increases in secondary BAs correlated with improved insulin sensitivity and post-OAGB increases in primary taurine-conjugated BAs correlated with higher fat mass preservation during weight loss.

Conclusions: RYGB and OAGB differentially modulate BA profiles over one year, with RYGB increasing secondary BAs and OAGB increasing taurine-conjugated primary BAs. These findings suggest distinct mechanisms contributing to their metabolic benefits.

目的:减肥手术是治疗肥胖最有效的长期治疗方法,但不同的手术技术如何影响代谢结果尚不清楚。胆汁酸(BAs)越来越被认为是代谢调节剂,在手术后餐后升高,可能介导其中的一些作用。本探索性研究探讨了Roux-en-Y胃旁路术(RYGB)和单吻合式胃旁路术(OAGB)在一年内对BA谱和相关代谢结果的不同影响。方法:45例肥胖患者(男性15例,女性30例,平均(SD)年龄46.6(7.1)岁)随机分为RYGB组(n = 24)和OAGB组(n = 20)。术前4-6周、术后6个月、12个月进行临床评估、体成分测量(双能x线吸收仪)、空腹血脂、炎症标志物、360分钟混合餐试验、口服葡萄糖耐量试验。在混合餐试验的8个时间点测量血浆总BAs和15个个体BAs (LC-MS)。结果:RYGB导致餐后继发性BAs从基线到12个月的增加(p = 0.004),特别是脱氧胆酸(DCA); p结论:RYGB和OAGB在一年内对BA谱有差异调节,RYGB增加继发性BAs, OAGB增加牛磺酸偶联的原发性BAs。这些发现表明了促进其代谢益处的不同机制。
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引用次数: 0
Intersectional inequality in general and central obesity: cross-sectional UK Biobank study. 一般和中心性肥胖的交叉不平等:英国生物银行的横断面研究。
IF 3.8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-05 DOI: 10.1038/s41366-025-01984-2
Joseph Hutchinson, Natalie Darko, Rebecca Hardy, David Webb, Francesco Zaccardi, William Johnson

Background: People exist at a combination of different individual and neighbourhood deprivations. Each of these combinations may have a unique impact on health. However, little is known about the intersectional inequality of these combinations on general and central obesity, including when considering their demographics. This study aims to answer these questions.

Methods: The sample comprised 452,339 participants from the UK Biobank study. Individuals were grouped into 320 intersectional strata according to their household income, neighbourhood deprivation, sex, ethnicity and age. Linear and logistic multilevel analysis of individual heterogeneity and discriminatory accuracy was used to establish the total, additive and interactive inequality of body mass index (BMI), fat mass index (FMI), and waist to height ratio (WHtR), as well as the associated obesity classifications.

Results: 6.5%, 25.2% and 9.1% of the total variation in BMI, FMI and WHtR, respectively, was due to inequality between the strata. Of this, 26.5%, 3.5% and 22.0% is interactive. 79, 58 and 93 strata for BMI, FMI and WHtR demonstrate a significant interactive effect. We found some patterns; for example, affluent white women have an advantaged interactive effect, whilst deprived black women have a disadvantaged effect. Meanwhile men experience the inverse relationship. The relationship between individual and neighbourhood deprivation is not universally experienced by all strata. For example, black men living in areas of high deprivation have higher BMIs as their household income increases.

Conclusions: A large proportion of variation in general and central obesity is due to intersectional inequality, with up to 26.5% being interactive. It is important that these intersectional effects are considered when designing policy interventions to avoid policy failure, such as by focussing on groups with high total and interactive risk.

背景:人们存在于不同的个人和社区剥夺的组合中。每一种组合都可能对健康产生独特的影响。然而,人们对这些组合在一般肥胖和中心性肥胖上的交叉不平等知之甚少,包括在考虑其人口统计学时。本研究旨在回答这些问题。方法:样本包括来自英国生物银行研究的452,339名参与者。根据家庭收入、邻里贫困、性别、种族和年龄,个人被分为320个交叉阶层。采用个体异质性和判别精度的线性和logistic多水平分析,建立体重指数(BMI)、脂肪质量指数(FMI)和腰高比(WHtR)的总不平等、加性不平等和交互不平等,以及相关的肥胖分类。结果:在BMI、FMI和WHtR的总变异中,分别有6.5%、25.2%和9.1%是由于层间不平等造成的。其中,26.5%,3.5%和22.0%是互动的。79、58和93层的BMI、FMI和WHtR表现出显著的交互效应。我们发现了一些模式;例如,富裕的白人女性具有有利的互动效应,而贫困的黑人女性具有不利的互动效应。而男性则是相反的关系。个人和邻里贫困之间的关系并不是所有阶层都普遍存在的。例如,生活在高度贫困地区的黑人男性,随着家庭收入的增加,他们的bmi指数也会更高。结论:全身性和中心性肥胖的很大一部分变异是由于交叉不平等造成的,其中高达26.5%是相互作用的。在设计政策干预措施以避免政策失败时,重要的是要考虑这些交叉效应,例如通过关注具有高总风险和互动风险的群体。
{"title":"Intersectional inequality in general and central obesity: cross-sectional UK Biobank study.","authors":"Joseph Hutchinson, Natalie Darko, Rebecca Hardy, David Webb, Francesco Zaccardi, William Johnson","doi":"10.1038/s41366-025-01984-2","DOIUrl":"https://doi.org/10.1038/s41366-025-01984-2","url":null,"abstract":"<p><strong>Background: </strong>People exist at a combination of different individual and neighbourhood deprivations. Each of these combinations may have a unique impact on health. However, little is known about the intersectional inequality of these combinations on general and central obesity, including when considering their demographics. This study aims to answer these questions.</p><p><strong>Methods: </strong>The sample comprised 452,339 participants from the UK Biobank study. Individuals were grouped into 320 intersectional strata according to their household income, neighbourhood deprivation, sex, ethnicity and age. Linear and logistic multilevel analysis of individual heterogeneity and discriminatory accuracy was used to establish the total, additive and interactive inequality of body mass index (BMI), fat mass index (FMI), and waist to height ratio (WHtR), as well as the associated obesity classifications.</p><p><strong>Results: </strong>6.5%, 25.2% and 9.1% of the total variation in BMI, FMI and WHtR, respectively, was due to inequality between the strata. Of this, 26.5%, 3.5% and 22.0% is interactive. 79, 58 and 93 strata for BMI, FMI and WHtR demonstrate a significant interactive effect. We found some patterns; for example, affluent white women have an advantaged interactive effect, whilst deprived black women have a disadvantaged effect. Meanwhile men experience the inverse relationship. The relationship between individual and neighbourhood deprivation is not universally experienced by all strata. For example, black men living in areas of high deprivation have higher BMIs as their household income increases.</p><p><strong>Conclusions: </strong>A large proportion of variation in general and central obesity is due to intersectional inequality, with up to 26.5% being interactive. It is important that these intersectional effects are considered when designing policy interventions to avoid policy failure, such as by focussing on groups with high total and interactive risk.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145906051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Capturing metabolic syndrome: new thresholds for insulin resistance and novel body composition indices. 捕获代谢综合征:胰岛素抵抗的新阈值和新的身体成分指数。
IF 3.8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-03 DOI: 10.1038/s41366-025-01993-1
Francesco Frigerio, Alessia Vitozzi, Claudia Piciocchi, Federico Ricci, Maria De Marinis, Valeria Galfano, Carla Lubrano, Stefania Mariani, Elena Gangitano, Marianna Minnetti, Luca Muzzioli, Andrea Lenzi, Massimiliano Caprio, Andrea M Isidori, Lucio Gnessi, Silvia Migliaccio, Mario Siervo, Lorenzo Maria Donini, Eleonora Poggiogalle

Background: Despite being a defining feature of metabolic syndrome (MetS), clinical assessment of IR remains challenging, due to the costs of reference methods and the numerosity of IR indices. Furthermore, to which extent IR contributes to MetS, while controlling for altered body composition, is still largely unexplored.

Objectives: The present work aims at proposing new cut points for IR among people with overweight and obesity, assessing the concordance of different IR definitions and investigating how IR interacts with body composition in predicting MetS status.

Subjects: 665 patients were assessed for potential enrolment, using a cross-sectional design. The following inclusion criteria were applied: age ≥18 years, body mass index ≥25 kg/m2, White European, no fulfilled criterion for diabetes mellitus, no current pregnancy.

Methods: Concordance of previously validated IR definitions was assessed by Cohen's κ. ROC curve analysis with 5-fold cross-validation was used to determine novel cut points for IR indices based on MetS presence. Finally, mediation analysis was employed to test whether IR mediates the relationship between body composition indices (i.e., fat mass-to-fat-free mass ratio, FM:FFM and appendicular lean soft tissue-to-visceral fat area ratio, ALST:VFA) and MetS.

Results: A total of 515 patients were included in the final analysis (females: 80.9%; MetS prevalence: 40%). Overall, IR definitions which previously validated against the hyperinsulinemic-euglycemic clamp displayed the highest level of agreement. The following cut-points were identified from ROC curve analysis: ISI-Matsuda<3.33 (AUROC = 0.675, p < 0.001), HOMA-IR > 2.93 (AUROC = 0.663 p < 0.001), HOMA2-IR > 1.67 (AUROC = 0.651 p < 0.001). Finally, ALST:VFA but not FM:FFM significantly predicted MetS status independent of age, with the mediating role of ISI-Matsuda, HOMA-IR and HOMA2-IR.

Conclusions: IR indices mediated the effect of altered body composition (i.e., reduced appendicular muscularity and increased visceral adiposity) on MetS. Newly proposed diagnostic thresholds can aid in the identification of IR among patients at increased cardio-metabolic risk.

背景:尽管IR是代谢综合征(MetS)的定义特征,但由于参考方法的成本和IR指标的数量众多,临床评估仍然具有挑战性。此外,在控制身体成分改变的情况下,IR对MetS的贡献程度仍未得到充分研究。目的:目前的工作旨在提出超重和肥胖人群中IR的新切入点,评估不同IR定义的一致性,并研究IR如何与身体成分相互作用以预测MetS状态。受试者:采用横断面设计对665例患者进行潜在入组评估。纳入标准:年龄≥18岁,体重指数≥25 kg/m2,白种欧洲人,未满足糖尿病标准,无妊娠史。方法:采用Cohen’s κ法评估先前确认的IR定义的一致性。使用5倍交叉验证的ROC曲线分析来确定基于MetS存在的IR指数的新切点。最后,采用中介分析检验IR是否介导体成分指数(即脂肪质量与无脂质量比、FM:FFM和阑尾瘦软组织与内脏脂肪面积比、ALST:VFA)与MetS之间的关系。结果:最终分析共纳入515例患者(女性:80.9%;MetS患病率:40%)。总的来说,先前对高胰岛素-血糖钳钳进行验证的IR定义显示出最高水平的一致性。从ROC曲线分析中确定了以下切点:ISI-Matsuda 2.93 (AUROC = 0.663 p) 1.67 (AUROC = 0.651 p)结论:IR指数介导了身体成分改变(即阑尾肌肉减少和内脏脂肪增加)对MetS的影响。新提出的诊断阈值有助于在心脏代谢风险增加的患者中识别IR。
{"title":"Capturing metabolic syndrome: new thresholds for insulin resistance and novel body composition indices.","authors":"Francesco Frigerio, Alessia Vitozzi, Claudia Piciocchi, Federico Ricci, Maria De Marinis, Valeria Galfano, Carla Lubrano, Stefania Mariani, Elena Gangitano, Marianna Minnetti, Luca Muzzioli, Andrea Lenzi, Massimiliano Caprio, Andrea M Isidori, Lucio Gnessi, Silvia Migliaccio, Mario Siervo, Lorenzo Maria Donini, Eleonora Poggiogalle","doi":"10.1038/s41366-025-01993-1","DOIUrl":"https://doi.org/10.1038/s41366-025-01993-1","url":null,"abstract":"<p><strong>Background: </strong>Despite being a defining feature of metabolic syndrome (MetS), clinical assessment of IR remains challenging, due to the costs of reference methods and the numerosity of IR indices. Furthermore, to which extent IR contributes to MetS, while controlling for altered body composition, is still largely unexplored.</p><p><strong>Objectives: </strong>The present work aims at proposing new cut points for IR among people with overweight and obesity, assessing the concordance of different IR definitions and investigating how IR interacts with body composition in predicting MetS status.</p><p><strong>Subjects: </strong>665 patients were assessed for potential enrolment, using a cross-sectional design. The following inclusion criteria were applied: age ≥18 years, body mass index ≥25 kg/m<sup>2</sup>, White European, no fulfilled criterion for diabetes mellitus, no current pregnancy.</p><p><strong>Methods: </strong>Concordance of previously validated IR definitions was assessed by Cohen's κ. ROC curve analysis with 5-fold cross-validation was used to determine novel cut points for IR indices based on MetS presence. Finally, mediation analysis was employed to test whether IR mediates the relationship between body composition indices (i.e., fat mass-to-fat-free mass ratio, FM:FFM and appendicular lean soft tissue-to-visceral fat area ratio, ALST:VFA) and MetS.</p><p><strong>Results: </strong>A total of 515 patients were included in the final analysis (females: 80.9%; MetS prevalence: 40%). Overall, IR definitions which previously validated against the hyperinsulinemic-euglycemic clamp displayed the highest level of agreement. The following cut-points were identified from ROC curve analysis: ISI-Matsuda<3.33 (AUROC = 0.675, p < 0.001), HOMA-IR > 2.93 (AUROC = 0.663 p < 0.001), HOMA2-IR > 1.67 (AUROC = 0.651 p < 0.001). Finally, ALST:VFA but not FM:FFM significantly predicted MetS status independent of age, with the mediating role of ISI-Matsuda, HOMA-IR and HOMA2-IR.</p><p><strong>Conclusions: </strong>IR indices mediated the effect of altered body composition (i.e., reduced appendicular muscularity and increased visceral adiposity) on MetS. Newly proposed diagnostic thresholds can aid in the identification of IR among patients at increased cardio-metabolic risk.</p>","PeriodicalId":14183,"journal":{"name":"International Journal of Obesity","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Is lower extremity joint replacement surgery associated with weight loss? An institutional retrospective study of 36,993 cases. 下肢关节置换手术与体重减轻有关吗?对36,993例病例进行机构回顾性研究。
IF 3.8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-03 DOI: 10.1038/s41366-025-02014-x
Renee Ren, Periklis Giannakis, Haoyan Zhong, Jashvant Poeran, Alex Illescas, Crispiana Cozowicz, Lisa Reisinger, Stavros G Memtsoudis, Jiabin Liu

Total joint arthroplasty (TJA), including total hip (THA) and knee arthroplasty (TKA), improves mobility and quality of life. While often assumed to promote weight loss, evidence on long-term weight change remains mixed. In this large retrospective cohort study of 36,993 adults undergoing primary TJA at a tertiary academic center (2016-2021), we characterize weight and BMI changes following TJA, and identify postoperative weight patterns across preoperative BMI subgroups. BMI and weight were recorded at surgery and at routine 3-month postoperative intervals. Patients were stratified by baseline BMI to assess weight trajectories across subgroups (<25, 25 to <30, 30 to <35, 35 to <40, ≥40 kg/m²). Both THA and TKA patients demonstrated modest short-term BMI reductions within 1-3 months (-0.55% and -1.15%, respectively). However, by 13-15 months, net BMI change approached baseline for THA (-0.09%) and TKA (-0.65%). Patients with BMI ≥ 40 kg/m² exhibited the greatest initial loss (-1.30%) but later rebounded above baseline (+0.21%). Across all BMI groups, absolute changes in BMI and body weight were minimal, with an inflection toward weight regain at 7-9 months. Thus, TJA does not necessarily drive clinically meaningful or lasting weight loss, underscoring the importance of integrated perioperative weight-management strategies, particularly for patients with obesity.

全关节置换术(TJA),包括全髋关节(THA)和膝关节置换术(TKA),可改善活动能力和生活质量。虽然通常被认为可以促进减肥,但长期体重改变的证据仍然喜忧参半。在这项大型回顾性队列研究中,研究人员在某三级学术中心(2016-2021)对36,993名接受原发性TJA的成年人进行了研究,研究人员描述了TJA后体重和BMI的变化,并确定了术前BMI亚组的术后体重模式。在手术时和术后常规3个月间隔记录BMI和体重。根据基线BMI对患者进行分层,以评估各亚组的体重轨迹(
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引用次数: 0
The effect of resveratrol supplementation on anthropometric indices, adiponectin and leptin levels in individuals with overweight and obesity: a graded, systematic review and meta-analysis of randomized controlled trials. 补充白藜芦醇对超重和肥胖个体的人体测量指数、脂联素和瘦素水平的影响:随机对照试验的分级、系统评价和荟萃分析。
IF 3.8 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-12-27 DOI: 10.1038/s41366-025-01994-0
Azin Setayesh, Pishva Arzhang, Mohammadreza Moradi Baniasadi, Maryam Lahouti, Leila Azadbakht

Background: The effects of resveratrol supplementation on anthropometric indices, adiponectin, and leptin levels remain inconclusive in individuals with overweight and obesity.

Method: This systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effects of resveratrol supplementation on anthropometric indices, adiponectin, and leptin levels. We searched electronic databases, including Scopus, Web of Science, and PubMed, up to September 2025, to identify eligible RCTs.

Results: A total of 23 RCTs, involving 1005 participants, met the inclusion criteria for the meta-analysis. Resveratrol supplementation did not significantly affect body weight (WMD: -1.42 kg; 95% CI: -3.19, 0.35; P = 0.117), body mass index (BMI) (WMD: -0.47 kg/m²; 95% CI: -0.96, 0.01; P = 0.055), fat mass (FM) (WMD: 0.47 kg; 95% CI: -1.75, 2.69; P = 0.679), body fat percentage (BFP) (WMD: -0.88%; 95% CI: -1.91, 0.15; P = 0.094), fat-free mass (FFM) (WMD: 1.42 kg; 95% CI: -1.04, 3.89; P = 0.257), waist-hip ratio (WHR) (WMD: -0.00; 95% CI: -0.01, 0.00; P = 0.436), adiponectin (WMD: 1.84 µg/mL; 95% CI: -2.25, 5.95; P = 0.378), or leptin (WMD: 1.87 ng/mL; 95% CI: -3.84, 7.60; P = 0.521). However, resveratrol supplementation significantly reduced waist circumference (WC) (WMD: -1.93 cm; 95% CI: -3.10, -0.76; P = 0.001). Subgroup analyses revealed significant reductions in body weight and BMI with doses <1000 mg/day, longer interventions (≥12 weeks), and in females. Additionally, FFM increased significantly among participants aged <50 years, and leptin levels were significantly elevated in both sexes.

Conclusion: This meta-analysis showed that resveratrol supplementation did not significantly impact most anthropometric measures and serum leptin and adiponectin in individuals with overweight and obesity. However, it led to a significant reduction in waist circumference. The PROSPERO registration number: is CRD42024497932.

背景:在超重和肥胖人群中,补充白藜芦醇对人体测量指数、脂联素和瘦素水平的影响仍不确定。方法:本研究对随机对照试验(rct)进行系统回顾和荟萃分析,以评估补充白藜芦醇对人体测量指标、脂联素和瘦素水平的影响。我们检索了截止到2025年9月的电子数据库,包括Scopus、Web of Science和PubMed,以确定符合条件的rct。结果:共有23项rct,涉及1005名受试者,符合meta分析的纳入标准。白藜芦醇补充剂并没有显着影响的体重(大规模杀伤性武器:-1.42公斤;95%置信区间CI: -3.19, 0.35; P = 0.117),身体质量指数(BMI)(大规模杀伤性武器:-0.47公斤/ m²;95%置信区间CI: -0.96, 0.01; P = 0.055),脂肪量(FM)(大规模杀伤性武器:0.47公斤;95%置信区间CI: -1.75, 2.69; P = 0.679),体脂百分比(桶)(大规模杀伤性武器:-0.88%;95%置信区间:-1.91,0.15;P = 0.094),无脂质量(FFM)(大规模杀伤性武器:1.42公斤;95%置信区间CI: -1.04, 3.89; P = 0.257),腰臀比(WHR)(大规模杀伤性武器:-0.00;95%置信区间CI: -0.01, 0.00; P = 0.436),脂联素(大规模杀伤性武器:1.84µg / mL;95% ci: -2.25, 5.95;瘦素(P = 0.378),或大规模杀伤性武器:1.87 ng / mL; 95%置信区间CI: -3.84, 7.60; P = 0.521)。然而,补充白藜芦醇可显著降低腰围(WC) (WMD: -1.93 cm; 95% CI: -3.10, -0.76; P = 0.001)。结论:本荟萃分析显示,在超重和肥胖人群中,补充白藜芦醇对大多数人体测量指标和血清瘦素和脂联素没有显著影响。然而,它导致了腰围的显著减少。普洛斯彼罗注册号:CRD42024497932。
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引用次数: 0
期刊
International Journal of Obesity
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