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Association between assisted reproductive technology and gestational diabetes mellitus: the role of serum folate and triglycerides. 辅助生殖技术与妊娠期糖尿病的关系:血清叶酸和甘油三酯的作用。
IF 5.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-03-07 DOI: 10.1038/s41387-026-00414-0
Bin Zhang, Sijie Xi, Runrun Hao, Zhaolong Zhan, Zhonghua Shi, Xiaosong Yuan

Background: Women conceiving via assisted reproductive technology (ART) may have a higher risk of developing gestational diabetes mellitus (GDM) compared to those who conceive spontaneously. However, the underlying factors associated with this relationship are not fully understood. This study aimed to investigate the association between ART conception and GDM prevalence and to explore related maternal serum biomarkers.

Methods: In an observational cohort of 11,563 singleton pregnancies, GDM was diagnosed at 24-28 weeks. We compared maternal characteristics, GDM prevalence, and late-pregnancy serum levels of folate, vitamin B12, and lipids between ART and spontaneously conceived women. Multivariable logistic regression assessed the independent association between ART and GDM.

Results: Among the participants, 2.3% conceived through ART. The overall GDM prevalence was 8.4%, but significantly higher in the ART group (15.0%). Within the ART group, GDM was more common among women with advanced age (23.2%), obesity (21.8%), or multiparity (25.0%). After adjustment for confounders, ART conception remained independently associated with an increased prevalence of GDM (adjusted OR: 1.49, 95% CI: 1.03-2.15). Furthermore, women in the ART group had significantly higher adjusted serum levels of folate (adjusted β = 3.58, 95% CI: 1.96-5.21) and triglycerides (adjusted β = 0.25, 95% CI: 0.13-0.37) compared to the spontaneous conception group. In the entire cohort, higher levels of both folate (adjusted OR = 2.21, 95% CI: 1.71-2.85) and triglycerides (adjusted OR = 1.70, 95% CI: 1.31-2.22) were independently associated with an increased GDM prevalence.

Conclusions: Our study confirms that ART pregnancies are associated with a higher risk of GDM and with elevated circulating folate and triglyceride concentrations at delivery. These findings highlight the importance of monitoring GDM risk and metabolic profiles in pregnancies achieved through ART. Future studies with biomarker assessments earlier in gestation are needed to clarify whether maternal folate and lipid metabolism contribute causally to the excess risk of GDM in ART pregnancies.

背景:与自然受孕的女性相比,通过辅助生殖技术(ART)受孕的女性患妊娠期糖尿病(GDM)的风险更高。然而,与这种关系相关的潜在因素尚未完全了解。本研究旨在探讨ART受孕与GDM患病率之间的关系,并探讨相关的母体血清生物标志物。方法:在11,563例单胎妊娠的观察队列中,GDM在24-28周被诊断。我们比较了ART和自然受孕妇女的产妇特征、GDM患病率、妊娠后期血清叶酸、维生素B12和血脂水平。多变量logistic回归评估ART与GDM之间的独立关联。结果:参与者中,2.3%通过ART受孕。总体GDM患病率为8.4%,但ART组明显更高(15.0%)。在ART组中,GDM在高龄(23.2%)、肥胖(21.8%)或多胎(25.0%)女性中更为常见。校正混杂因素后,ART受孕仍然与GDM患病率增加独立相关(校正OR: 1.49, 95% CI: 1.03-2.15)。此外,与自然受孕组相比,ART组的妇女血清中叶酸(调整后的β = 3.58, 95% CI: 1.96-5.21)和甘油三酯(调整后的β = 0.25, 95% CI: 0.13-0.37)的调整水平显著高于自然受孕组。在整个队列中,较高水平的叶酸(校正OR = 2.21, 95% CI: 1.71-2.85)和甘油三酯(校正OR = 1.70, 95% CI: 1.31-2.22)与GDM患病率增加独立相关。结论:我们的研究证实,ART妊娠与GDM的高风险以及分娩时循环叶酸和甘油三酯浓度升高有关。这些发现强调了通过抗逆转录病毒治疗妊娠监测GDM风险和代谢特征的重要性。未来的研究需要在妊娠早期进行生物标志物评估,以澄清母体叶酸和脂质代谢是否导致ART妊娠中GDM的过度风险。
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引用次数: 0
Nutritional contents, nutritional quality and manufacturer of ready foods in China: a cross-sectional study of 2087 food products. 中国即食食品的营养成分、营养质量与生产企业:对2087种食品的横断面研究
IF 5.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-03-02 DOI: 10.1038/s41387-026-00413-1
Tengyi Wang, Yuze Xin, Xinyan Liu, Pengpeng Ye, Shuangjie Peng, Shiwenqian Yin, Jinyu Liang, Leon Booth, Kristy Law, Kathy K Trieu, Simone Pettigrew, Jason Hy Wu, Maoyi Tian

Background: China's rapid economic development and urbanisation have led to significant shifts in dietary habits, moving from home-cooked meals to ready foods. This transition may exacerbate the burden of non-communicable diseases.

Objective: This study aimed to (i) assess the overall nutritional quality and quantities of specific nutrients of ready foods available from Chinese online stores, (ii) evaluate whether these foods comply with national dietary recommendations, and (iii) determine whether the nutritional quality of ready foods differs across manufacturers.

Methods: This cross-sectional study analysed ready foods from four major Chinese online stores: Taobao, JD.com, Suning, and Vipshop. Ready foods include pre-packaged, partially processed foods requiring minimal cooking or reheating before consumption. The nutritional quality was calculated based on the amount of dietary fibre, saturated fat, protein, sugar, sodium, and energy of the product by using the Health Star Rating (HSR) scoring algorithm. Continuous and categorical variables are described using means (standard deviation [SD]) or median (inter-quartile range [IQR]) and proportions respectively.

Results: We identified 109 419 products from the four major online stores, with 2 087 products included in analyses after conducting eligibility checks and removing duplicates. Median nutritional values for all ready foods were as follows: energy content 2203.3 kJ (IQR 2055.6-3222.5), protein content 29.2 g (IQR 14.9-51.5), fat content 35.5 g (IQR 17.0-57.4), carbohydrate content 15.5 g (IQR 5.8-45.6), and sodium content 1733.6 mg (IQR 995.7-3287.1). Only 25.3% of products met the estimated energy recommended range according to the Chinese dietary reference intakes and more than 85.6% exceeded the recommended sodium intake according to Chinese dietary guidelines. The mean HSR was 2.7 (SD = 0.9), and less than half (32.9%) were classified as healthy products (HSR ≥ 3.5).

Conclusions: Many of the assessed Chinese ready foods failed to meet national dietary recommendations for nutrient composition and exhibited overall low overall nutritional quality. Potential strategies to combat the growing burden of diet-related non-communicable diseases include (i) enhancing consumer awareness about the nutritional aspects of ready foods, (ii) encouraging the food industry to reformulate products, and (iii) supporting consumers to choose healthier options.

背景:中国快速的经济发展和城市化导致了饮食习惯的重大转变,从家常菜转向即食食品。这种转变可能加剧非传染性疾病的负担。目的:本研究旨在(i)评估中国在线商店出售的即食食品的整体营养质量和特定营养素的数量,(ii)评估这些食品是否符合国家膳食建议,以及(iii)确定不同制造商的即食食品的营养质量是否不同。方法:本横断面研究分析了中国四大在线商店:淘宝、京东、苏宁和唯品会的即食食品。即食食品包括预先包装的,部分加工的食品,在食用前需要最少的烹饪或重新加热。采用健康之星评分(Health Star Rating, HSR)算法,根据产品膳食纤维、饱和脂肪、蛋白质、糖、钠和能量的含量计算营养品质。连续变量和分类变量分别使用均值(标准差[SD])或中位数(四分位数间距[IQR])和比例来描述。结果:我们从四个主要的在线商店中识别出109419种产品,在进行资格检查和删除重复后,将2087种产品纳入分析。所有即食食品的营养价值中位数如下:能量含量2203.3 kJ (IQR 2055.6-3222.5),蛋白质含量29.2 g (IQR 14.9-51.5),脂肪含量35.5 g (IQR 17.0-57.4),碳水化合物含量15.5 g (IQR 5.8-45.6),钠含量1733.6 mg (IQR 995.7-3287.1)。只有25.3%的产品符合中国膳食参考摄入量的估计能量推荐范围,超过85.6%的产品超过中国膳食指南的推荐钠摄入量。平均HSR为2.7 (SD = 0.9),不到一半(32.9%)被归类为健康产品(HSR≥3.5)。结论:许多被评估的中国即食食品的营养成分不符合国家膳食建议,整体营养质量较低。应对与饮食有关的非传染性疾病日益加重的负担的潜在战略包括:(一)提高消费者对即食食品营养方面的认识,(二)鼓励食品工业重新配制产品,以及(三)支持消费者选择更健康的选择。
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引用次数: 0
Heterogeneous effect of saxagliptin on glucose fluctuation and β-cell function in T1DM: a multicentre, randomised trial. 沙格列汀对T1DM患者血糖波动和β细胞功能的异质性影响:一项多中心随机试验
IF 5.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-03-02 DOI: 10.1038/s41387-026-00411-3
Yun Shi, Min Shen, Yong Gu, Yang Chen, Kuanfeng Xu, Ji Hu, Chen Fang, Heming Guo, Ning Xu, Guofeng Wang, Weiping Lu, Sha Tao, Songqing Zhao, Chengxia Fang, Jianhua Ma, Rengna Yan, Rui Sun, Li Qian, Chenguang Wu, Hui Jiang, Tao Yang

Background and aims: We aimed to explore whether saxagliptin, a dipeptidyl peptidase-IV inhibitor, could ameliorate glucose fluctuations and maintain β-cell function in T1DM.

Methods and results: A multicentre, open-label, randomised trial was performed, including 184 T1DM patients from six medical centres. These patients received insulin with or without saxagliptin at 5 mg per day for 24 weeks. The primary endpoint was the change from the baseline value of the MAGE, as measured by a CGMS after 24 weeks. The secondary endpoints included the change from baseline value of islet function during the 3-hour BMTT, HbA1c, and insulin dosage. The exploratory analysis was the influence of SNPs in the incretin-related genes on saxagliptin treatment outcomes. No differences were observed between the two groups in MAGE after treatment for 24 weeks. The change of C-peptidemax levels from baseline to 24 weeks in SAXA group (insulin plus saxagliptin) was higher than in CONT group (insulin only) [p = 0.040]. No difference were observed between the groups in HbA1c, insulin dosage after 24 weeks. In SAXA group, rs10305439, rs10305441 of GLP1R and rs6233 of PCSK1/3 were associated with HbA1c response (p = 0.026, 0.019, and 0.048 respectively); the G allele of rs2143734 of GLP1R were associated with lower change of fasting C-peptide from baseline (p = 0.029) CONCLUSIONS: The saxagliptin did not ameliorate glucose fluctuations; however, it appeared to maintain β-cell function to some extent, and SNPs in the incretin-related gene may indicate responsiveness to DPP-IV inhibitors in T1DM.

Clinicaltrials: Gov number, NCT02307695.

背景与目的:我们旨在探讨沙格列汀(一种二肽基肽酶- iv抑制剂)是否能改善T1DM患者的血糖波动并维持β细胞功能。方法和结果:进行了一项多中心、开放标签、随机试验,包括来自6个医疗中心的184名T1DM患者。这些患者接受沙格列汀联合或不联合胰岛素治疗,每天5mg,持续24周。主要终点是24周后CGMS测量的MAGE基线值的变化。次要终点包括3小时BMTT期间胰岛功能基线值的变化、HbA1c和胰岛素剂量。探索性分析肠促胰岛素相关基因snp对沙格列汀治疗结果的影响。治疗24周后,两组间的MAGE无差异。从基线到24周,SAXA组(胰岛素+沙格列汀)C-peptidemax水平的变化高于CONT组(仅胰岛素)[p = 0.040]。24周后各组HbA1c、胰岛素用量无差异。在SAXA组,GLP1R rs10305439、rs10305441和PCSK1/3 rs6233与HbA1c应答相关(p分别为0.026、0.019和0.048);GLP1R rs2143734的G等位基因与较基线较低的空腹c肽变化相关(p = 0.029)结论:沙格列汀没有改善血糖波动;然而,它似乎在一定程度上维持β细胞功能,肠促胰岛素相关基因的snp可能表明T1DM患者对DPP-IV抑制剂的反应性。临床试验:政府编号:NCT02307695。
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引用次数: 0
The association between steatotic liver disease and chronic kidney disease: a meta-analysis and Mendelian randomization study highlighting metabolic comorbidities. 脂肪变性肝病和慢性肾脏疾病之间的关系:一项荟萃分析和孟德尔随机化研究,强调代谢合并症。
IF 5.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-02-23 DOI: 10.1038/s41387-026-00412-2
Xiang Ji, Jinguo Jiang, Yunyun Liu, Liuxin Li, Honghao Yang, Zheng Ma, Chenying Wang, Tingjing Zhang, Yuhong Zhao, Yashu Liu, Yang Xia

Steatotic liver disease (SLD)-a term encompassing nonalcoholic fatty liver disease (NAFLD), metabolic-associated fatty liver disease (MAFLD), and metabolic dysfunction-associated steatotic liver disease (MASLD)-and chronic kidney disease (CKD) are major global health concerns. Metabolic factors, including obesity, type 2 diabetes, hypertension, and dyslipidemia, are integral to the definitions of MAFLD and MASLD and may confound their association with CKD. This study aimed to update a meta-analysis on the association between SLD and CKD risk and to conduct a two-sample Mendelian randomization (MR) analysis to explore the causal roles of SLD and metabolic factors in CKD. We systematically searched PubMed, Embase, and Web of Science up to November 5, 2024, for eligible studies. Random-effects models were used to pool odds ratios (ORs) with 95% confidence intervals (CIs). Two-sample MR was performed using the inverse-variance weighted (IVW) method as the primary model, with additional methods applied for sensitivity analyses. A total of 34 studies involving 3,783,136 participants were included in the meta-analysis. The results demonstrated significant positive associations between MAFLD, NAFLD, and MASLD with CKD (MAFLD: OR 1.41 [1.07-1.84], RR 1.64 [1.39-1.94], HR 1.64 [1.39-1.94]; NAFLD: OR 1.19 [1.08-1.31], RR 1.66 [1.45-1.91], HR 1.43 [1.31-1.55]; MASLD: HR 1.34 [1.08-1.67]). These findings support a significant association between SLD (MAFLD, NAFLD, and MASLD) and an increased risk of CKD. However, Mendelian randomization (MR) analysis found no causal effect of SLD on CKD risk. In contrast, genetically predicted metabolic factors-including body mass index (BMI), waist circumference, type 2 diabetes, systolic and diastolic blood pressure, triglycerides, and high-density lipoprotein cholesterol-were significantly associated with an increased CKD risk. These findings suggest that metabolic dysfunction, rather than SLD itself, may be the main driver of CKD risk. This underscores the clinical importance of early screening and intervention for metabolic health in patients with SLD to reduce the burden of CKD.

脂肪变性肝病(SLD)是一个涵盖非酒精性脂肪性肝病(NAFLD)、代谢相关脂肪性肝病(MAFLD)、代谢功能障碍相关脂肪性肝病(MASLD)和慢性肾脏疾病(CKD)的术语,是全球主要的健康问题。代谢因素,包括肥胖、2型糖尿病、高血压和血脂异常,是MAFLD和MASLD定义的组成部分,可能混淆它们与CKD的关联。本研究旨在更新一项关于SLD与CKD风险之间关联的荟萃分析,并进行双样本孟德尔随机化(MR)分析,以探讨SLD和代谢因素在CKD中的因果作用。我们系统地检索了PubMed, Embase和Web of Science,直到2024年11月5日,以获得符合条件的研究。随机效应模型采用95%置信区间(ci)合并优势比(ORs)。采用反方差加权(IVW)方法作为主要模型进行双样本MR,并采用其他方法进行敏感性分析。meta分析共纳入34项研究,涉及3,783,136名参与者。结果显示,MAFLD、NAFLD和MASLD与CKD之间存在显著正相关(MAFLD: OR 1.41 [1.07-1.84], RR 1.64 [1.39-1.94], HR 1.64 [1.39-1.94]; NAFLD: OR 1.19 [1.08-1.31], RR 1.66 [1.45-1.91], HR 1.43 [1.31-1.55]; MASLD: HR 1.34[1.08-1.67])。这些发现支持SLD (MAFLD、NAFLD和MASLD)与CKD风险增加之间的显著关联。然而,孟德尔随机化(MR)分析没有发现SLD与CKD风险的因果关系。相反,遗传预测的代谢因素——包括身体质量指数(BMI)、腰围、2型糖尿病、收缩压和舒张压、甘油三酯和高密度脂蛋白胆固醇——与CKD风险增加显著相关。这些发现表明,代谢功能障碍,而不是SLD本身,可能是CKD风险的主要驱动因素。这强调了早期筛查和干预SLD患者代谢健康以减轻CKD负担的临床重要性。
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引用次数: 0
The Beverage Quality Index and type 2 diabetes risk in women: a prospective analysis of the Mexican Teachers' Cohort. 饮料质量指数与女性2型糖尿病风险:墨西哥教师队列的前瞻性分析
IF 5.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-22 DOI: 10.1038/s41387-026-00410-4
Maria G Jacobo Cejudo, Adriana Monge, Neha Khandpur, Trudy Voortman, Dalia Stern, Johanna M Geleijnse

Background: Individual beverages have shown divergent associations with type 2 diabetes. Whether overall beverage quality affects diabetes risk is unknown. Therefore, we estimated the association of a previously developed Beverage Quality Index (BQI) with the incidence of diabetes in Mexican women.

Methods: We included 77,484 female participants from the Mexican Teachers' Cohort without diabetes at baseline (2006-2008). At baseline, diet was assessed using a 140-item food-frequency questionnaire. The BQI included seven components (coffee, milk, juices, sugar-sweetened beverages [SSBs], alcohol, sugar added to beverages, and energy from beverages), with a total theoretical score ranging from 0 to 70. A higher score represents a healthier beverage intake pattern. Data on diabetes incidence were available through 2018 from self-reports or cross-linkage with administrative data. We used multivariable Cox proportional-hazard models adjusted for potential confounders.

Results: Participants' mean (SD) baseline age was 45.9 (7.2) years, and BQI score was 37.3 (8.6), ranging from 9.8 to 69.3. During a median follow-up of 7.6 years, 4521 participants developed diabetes. After multivariable adjustment, when comparing extreme categories (≥55 vs. <25), a higher BQI was suggestively associated with lower diabetes incidence (HR: 0.87; 95% CI: 0.71, 1.06), although the estimate was imprecise. Restricted cubic spline analysis showed no association between the BQI and diabetes incidence (p-nonlinearity = 0.20).

Conclusions: In a cohort of Mexican women, the BQI for overall beverage quality showed no consistent association with diabetes incidence. Further research on beverage quality indices for Mexican populations, including those with high SSB intake, is warranted.

背景:不同的饮料与2型糖尿病之间存在不同的关联。整体饮料质量是否影响糖尿病风险尚不清楚。因此,我们估计了先前开发的饮料质量指数(BQI)与墨西哥女性糖尿病发病率的关系。方法:我们纳入了来自墨西哥教师队列的77,484名基线时无糖尿病的女性参与者(2006-2008)。在基线,饮食评估使用140项食物频率问卷。BQI包括7个组成部分(咖啡、牛奶、果汁、含糖饮料、酒精、饮料中添加的糖和饮料中的能量),理论总分从0到70不等。得分越高,表示饮料摄入模式越健康。截至2018年,糖尿病发病率的数据可通过自我报告或与行政数据交叉关联获得。我们使用针对潜在混杂因素调整的多变量Cox比例风险模型。结果:参与者的平均(SD)基线年龄为45.9(7.2)岁,BQI评分为37.3(8.6),范围从9.8到69.3。在中位7.6年的随访期间,4521名参与者患上了糖尿病。在多变量调整后,当比较极端类别(≥55 vs.结论:在墨西哥女性队列中,总体饮料质量的BQI与糖尿病发病率没有一致的关联。进一步研究墨西哥人口的饮料质量指数,包括那些高SSB摄入量,是有必要的。
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引用次数: 0
Relationships between diabetes, vitamin D status, depression, and Hispanic ethnicity: a project FRONTIER study. 糖尿病、维生素D状况、抑郁症和西班牙裔之间的关系:一项前沿项目研究。
IF 5.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2026-01-03 DOI: 10.1038/s41387-025-00409-3
Riley McCready, Claudia Morris, Philip Antwi-Adjei, Mohammed Pourghaed, Ashish Sarangi, Annette Boles, Felipe Ramirez-Velandia, Jonathan Kopel, John Culberson, Jonathan Singer, Gabriela Ashworth, Marwan N Sabbagh, Volker Neugebauer, Boris Decourt, Andrew C Shin, J Josh Lawrence

Background/objectives: Vitamin D (VD) status has been linked to the development of diabetes. However, this relationship in the context of comorbid conditions remains understudied. Additionally, ethnic disparities in nutritional status and chronic disease prevalence within rural populations are a vastly underrepresented area of research. In our previous study, we explored VD levels and depression in a rural West Texas aging sample. In the present study, we investigated the associations between diabetes, vitamin D (VD) levels, depression, and Hispanic ethnicity (HE) among a sample of aging, rural West Texans from Project FRONTIER (PF; Facing Rural Obstacles to Health Care Now Through Intervention, Education, and Research).

Subjects/methods: A cohort of 299 PF participants (mean age 62.6 ± 11.8 years old, 70.9% female, 40.5% HE) was used. We examined relationships between diabetes diagnosis, blood-based diabetes-related biomarkers, VD level, Geriatric Depression Scale (GDS) score, and HE status. We developed a "VD-sensitive GDS score" composed of the 9 GDS questions that were significantly correlated with VD level in our previous study. We further created a complementary "VD-insensitive GDS score" composed of the remaining 21 GDS questions. Standard correlation and regression analyses were employed.

Results: VD level was significantly negatively associated with diabetes diagnosis, while VD-sensitive depression score was significantly positively associated with diabetes diagnosis. HE was associated with higher HbA1c levels, higher fasting blood glucose levels, and higher VD-sensitive depression scores.

Conclusions: In this rural West Texas cohort, diabetes was significantly associated with low VD levels and high VD-sensitive depression scores. HE was associated with higher levels of diabetes-related biomarkers and higher VD-sensitive depression scores. These disparities are crucial to consider when examining areas for healthcare improvement in West Texas, particularly among aging populations.

背景/目的:维生素D (VD)水平与糖尿病的发生有关。然而,在合并症的情况下,这种关系仍未得到充分研究。此外,农村人口中营养状况和慢性病患病率的种族差异是一个代表性严重不足的研究领域。在我们之前的研究中,我们探讨了西德克萨斯州农村老龄化样本中的VD水平和抑郁症。在本研究中,我们调查了来自Project FRONTIER (PF;通过干预、教育和研究面对农村卫生保健障碍)的老年西德克萨斯人样本中糖尿病、维生素D (VD)水平、抑郁症和西班牙裔种族(HE)之间的关系。受试者/方法:299名PF参与者(平均年龄62.6±11.8岁,70.9%为女性,40.5%为男性)。我们研究了糖尿病诊断、基于血液的糖尿病相关生物标志物、VD水平、老年抑郁量表(GDS)评分和HE状态之间的关系。我们开发了一个“VD敏感GDS评分”,由我们之前研究中与VD水平显著相关的9个GDS问题组成。我们进一步创建了一个由其余21个GDS问题组成的补充“dvd不敏感GDS评分”。采用标准相关分析和回归分析。结果:VD水平与糖尿病诊断呈显著负相关,VD敏感抑郁评分与糖尿病诊断呈显著正相关。HE与较高的HbA1c水平、较高的空腹血糖水平和较高的vd敏感性抑郁评分相关。结论:在西德克萨斯农村队列中,糖尿病与低VD水平和高VD敏感抑郁评分显著相关。HE与较高水平的糖尿病相关生物标志物和较高的vd敏感抑郁评分相关。在检查西德克萨斯州的医疗保健改善区域时,特别是在老龄化人口中,这些差异是至关重要的。
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引用次数: 0
The promising effects of a multi-species synbiotic preparation on metabolic profile in elderly patients with type 2 diabetes and high cardiovascular risk: a randomized, triple-blind, placebo-controlled trial. 多物种合成制剂对老年2型糖尿病和心血管高危患者代谢谱的有希望的影响:一项随机、三盲、安慰剂对照试验
IF 5.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-12-18 DOI: 10.1038/s41387-025-00408-4
Neda Dolatkhah, Elnaz Nourizadeh, Naser Aghamohammadzadeh, Shahrzad Yahyavi, Fariba Eslamian, Maryam Hashemian

Background: Elderly patients with type 2 diabetes (T2DM) experience a significantly raised risk of cardiovascular disease. We aimed to determine the effect of the multi-species synbiotic supplementation in elderly patients with T2DM and high cardiovascular risk.

Methods: Ninety-six patients with T2DM, aged ≥65 years with high cardiovascular risk, were enrolled between January 2022 and May 2023 and randomly allocated to receive a synbiotic supplement, containing a multi-species probiotic, and fructooligosaccharide as a prebiotic, or placebo supplements for 4 months. The primary outcome was the mean difference in weight change between synbiotics and placebo. The secondary outcomes were the mean difference in modifications in the body fat mass (BFM), lean body mass (LBM), and biochemical parameters, including glucose metabolism indices, lipid profile, and adhesion molecules between the two groups due to the intervention.

Results: Eighty-five participants completed the study. The mean weight [-1.16 kg (-1.36 to -0.97)], body mass index (BMI) [-0.44 kg/m2 (-0.36 to -0.51)], and BFM [-0.99 kg (-1.05 to -0.93)] decreased significantly in the synbiotic group compared to the placebo group in the linear mixed analysis of covariance analysis (all p < 0.001). The mean serum Low-density-Lipoprotein (LDL-C) [-10.83 mg/dl (-14.78 to -6.88)], and total cholesterol [-11.78 mg/dl (-16.44 to -7.11)], vascular cell adhesion molecule 1 (VCAM-1) [-85.70 ng/L (-150.14 to -21.26)], fasting plasma glucose (FPG) [-22.83 mg/dl (-31.30 to -14.36)], and homeostatic model assessment for insulin resistance (HOMA-IR.) [-1.31 (-1.75 to -0.86)] improved in the synbiotic group significantly compared to the placebo group (p = 0.002, p = 0.012, p = 0.017, p < 0.001, p = 0.003 and p = 0.001, respectively). No serious adverse events were detected.

Conclusion: A multi-species synbiotic preparation benefits elderly patients with T2DM and high cardiovascular risk and improves weight, BMI, BFM, and plasma levels of total cholesterol, LDL-C, VCAM-1, FPG, and HOMA-IR. These findings suggest synbiotics may have health-promoting impacts in older patients with diabetes.

背景:老年2型糖尿病(T2DM)患者发生心血管疾病的风险显著增加。我们的目的是确定多物种合成补充剂对老年T2DM和心血管高危患者的影响。方法:在2022年1月至2023年5月期间,纳入96例年龄≥65岁、心血管高危的T2DM患者,随机分配接受4个月的含多种益生菌和低聚果糖作为益生元的合成补充剂或安慰剂补充剂。主要结果是合生剂和安慰剂之间体重变化的平均差异。次要结果是两组干预后体脂质量(BFM)、瘦体重(LBM)和生化参数(包括糖代谢指标、脂质谱和粘附分子)变化的平均差异。结果:85名参与者完成了研究。在协方差分析的线性混合分析中,与安慰剂组相比,合成制剂组的平均体重[-1.16 kg(-1.36 ~ -0.97)]、体重指数(BMI) [-0.44 kg/m2(-0.36 ~ -0.51)]和BFM [-0.99 kg(-1.05 ~ -0.93)]显著降低(均为p)。结论:多物种合成制剂有利于老年T2DM和心血管高危患者,改善体重、BMI、BFM、血浆总胆固醇、LDL-C、VCAM-1、FPG和HOMA-IR水平。这些发现表明,合生剂可能对老年糖尿病患者有促进健康的作用。
{"title":"The promising effects of a multi-species synbiotic preparation on metabolic profile in elderly patients with type 2 diabetes and high cardiovascular risk: a randomized, triple-blind, placebo-controlled trial.","authors":"Neda Dolatkhah, Elnaz Nourizadeh, Naser Aghamohammadzadeh, Shahrzad Yahyavi, Fariba Eslamian, Maryam Hashemian","doi":"10.1038/s41387-025-00408-4","DOIUrl":"10.1038/s41387-025-00408-4","url":null,"abstract":"<p><strong>Background: </strong>Elderly patients with type 2 diabetes (T2DM) experience a significantly raised risk of cardiovascular disease. We aimed to determine the effect of the multi-species synbiotic supplementation in elderly patients with T2DM and high cardiovascular risk.</p><p><strong>Methods: </strong>Ninety-six patients with T2DM, aged ≥65 years with high cardiovascular risk, were enrolled between January 2022 and May 2023 and randomly allocated to receive a synbiotic supplement, containing a multi-species probiotic, and fructooligosaccharide as a prebiotic, or placebo supplements for 4 months. The primary outcome was the mean difference in weight change between synbiotics and placebo. The secondary outcomes were the mean difference in modifications in the body fat mass (BFM), lean body mass (LBM), and biochemical parameters, including glucose metabolism indices, lipid profile, and adhesion molecules between the two groups due to the intervention.</p><p><strong>Results: </strong>Eighty-five participants completed the study. The mean weight [-1.16 kg (-1.36 to -0.97)], body mass index (BMI) [-0.44 kg/m<sup>2</sup> (-0.36 to -0.51)], and BFM [-0.99 kg (-1.05 to -0.93)] decreased significantly in the synbiotic group compared to the placebo group in the linear mixed analysis of covariance analysis (all p < 0.001). The mean serum Low-density-Lipoprotein (LDL-C) [-10.83 mg/dl (-14.78 to -6.88)], and total cholesterol [-11.78 mg/dl (-16.44 to -7.11)], vascular cell adhesion molecule 1 (VCAM-1) [-85.70 ng/L (-150.14 to -21.26)], fasting plasma glucose (FPG) [-22.83 mg/dl (-31.30 to -14.36)], and homeostatic model assessment for insulin resistance (HOMA-IR.) [-1.31 (-1.75 to -0.86)] improved in the synbiotic group significantly compared to the placebo group (p = 0.002, p = 0.012, p = 0.017, p < 0.001, p = 0.003 and p = 0.001, respectively). No serious adverse events were detected.</p><p><strong>Conclusion: </strong>A multi-species synbiotic preparation benefits elderly patients with T2DM and high cardiovascular risk and improves weight, BMI, BFM, and plasma levels of total cholesterol, LDL-C, VCAM-1, FPG, and HOMA-IR. These findings suggest synbiotics may have health-promoting impacts in older patients with diabetes.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":" ","pages":"2"},"PeriodicalIF":5.2,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12770592/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145781644","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
Umbelliferone preserves skin epidermal barrier integrity in diabetes-induced keratinocytes by regulating actin dynamics and suppressing ROS-mediated apoptosis. 伞花酮通过调节肌动蛋白动力学和抑制ros介导的细胞凋亡来保护糖尿病诱导的角质形成细胞的皮肤表皮屏障完整性。
IF 5.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-24 DOI: 10.1038/s41387-025-00407-5
Dong Yeon Kim, Young-Hee Kang, Min-Kyung Kang

Background: The skin serves as a fundamental protective barrier against environmental insults, with the epidermis, particularly the stratum corneum and tight junctions (TJs) connecting keratinocytes, playing a crucial role. Chronic hyperglycemia can impair these TJs, leading to compromised epidermal barrier function and diabetic skin complications. This study aimed to investigate the effects of umbelliferone on epidermal barrier function under type 2 diabetic conditions.

Methods: HaCaT keratinocytes were cultured under hyperglycemic conditions induced by 33 mM glucose with or without 1-20 μM umbelliferone to evaluate cellular protection and barrier-related protein regulation. Type 2 diabetic db/db mice were administered umbelliferone orally at 10 mg/kg per day for 10 weeks. The expression of epidermal barrier-related proteins in HaCaT cells and skin tissues was quantified by Western blot analysis.

Results: Umbelliferone enhanced multiple components essential for maintaining the skin barrier. It upregulated filaggrin, increased the expression of the TJ proteins ZO-1 and Occludin, and elevated AQP3 and HAS2 levels to support epidermal hydration, while reducing HYAL1 expression. Under impaired wound healing conditions induced by hyperglycemia, umbelliferone promoted cell migration via modulation of F-actin organization, Rho GTPase signaling, and integrin β1 expression. Additionally, it reduced ROS accumulation and alleviated high glucose-induced apoptosis.

Conclusions: Umbelliferone preserves epidermal barrier integrity by strengthening cell-cell junctions, enhancing hydration, promoting cell migration, and providing protection against oxidative stress and apoptosis. These findings suggest the therapeutic potential of umbelliferone in managing and preventing diabetic skin complications.

背景:皮肤是抵御环境侵害的基本保护屏障,表皮,特别是角质层和连接角质形成细胞的紧密连接(TJs)起着至关重要的作用。慢性高血糖可损害这些tj,导致表皮屏障功能受损和糖尿病性皮肤并发症。本研究旨在探讨伞花酮对2型糖尿病患者表皮屏障功能的影响。方法:在33 mM葡萄糖诱导的高血糖条件下培养HaCaT角化细胞,加或不加1-20 μM umbellliferone,评估细胞保护作用和屏障相关蛋白的调节作用。2型糖尿病db/db小鼠口服伞liferone,每天10mg /kg,持续10周。Western blot检测HaCaT细胞和皮肤组织中表皮屏障相关蛋白的表达。结果:伞花酮增强了维持皮肤屏障所必需的多种成分。它上调聚丝蛋白,增加TJ蛋白ZO-1和Occludin的表达,提高AQP3和HAS2水平,以支持表皮水化,同时降低HYAL1的表达。在高血糖导致的伤口愈合受损的情况下,伞草酮通过调节f -肌动蛋白组织、Rho GTPase信号传导和整合素β1的表达来促进细胞迁移。此外,它还能减少ROS的积累,减轻高糖诱导的细胞凋亡。结论:伞形花酮通过加强细胞间连接、增强水合作用、促进细胞迁移、抗氧化应激和细胞凋亡保护表皮屏障完整性。这些发现提示了伞形酮在管理和预防糖尿病皮肤并发症方面的治疗潜力。
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引用次数: 0
Global burden of 13 non-communicable diseases attributable to high fasting plasma glucose from the GBD 2021 study. GBD 2021研究中由高空腹血糖引起的13种非传染性疾病的全球负担
IF 5.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-24 DOI: 10.1038/s41387-025-00405-7
Junfeng Zhou, Zhengbin Yao, Shugen Xu, Yong Long, Zhao Zeng, Jiao Qin, Ning Ding, Yingjie Su

Background and objective: High fasting plasma glucose (HFPG) is a major risk factor for diseases, posing a serious public health challenge. This study examines the global burden of 13 non-communicable diseases (NCDs) attributed to HFPG.

Methods: We used the 2021 GBD Study to analyze deaths and DALYs linked to HFPG( > 4.90-5.30 mmol/L). Socio-Demographic Index (SDI) was used to assess development levels, with subgroup analyses by geography, year, gender, and SDI.

Results: In 2021, HFPG contributed to 5.15 million deaths and 151.95 million DALYs globally. From 1990 to 2021, the estimated annual percentage change (EAPC) in deaths and DALYs were 0.11 and 0.55, respectively. Diabetes, ischemic heart disease (IHD), and stroke accounted for the most deaths (1.66, 1.35, and 0.84 million). Liver cancer, chronic kidney disease (CKD), and pancreatic cancer showed the fastest mortality increases, with EAPCs of 1.90, 1.69, and 1.34, respectively. IHD and stroke had declining mortality burdens, with EAPCs of -0.13 and -0.98.

Conclusion: Over 30 years, HFPG-related NCDs have increased globally. Diabetes, IHD, and stroke remain the top burdens, while liver cancer, CKD, and pancreatic cancer are rising fastest. The disease burden in men is higher than in women, except for people with Alzheimer's disease and other dementias and people with blindness and vision loss (BVL).

背景与目的:高空腹血糖(HFPG)是疾病的主要危险因素,构成了严重的公共卫生挑战。本研究探讨了由HFPG引起的13种非传染性疾病(NCDs)的全球负担。方法:我们使用2021年GBD研究来分析与HFPG相关的死亡和DALYs (> 4.90-5.30 mmol/L)。社会人口指数(SDI)用于评估发展水平,并按地理、年份、性别和SDI进行亚组分析。结果:2021年,HFPG在全球造成515万人死亡和1.5195亿DALYs。从1990年到2021年,死亡和伤残调整生命年的估计年百分比变化(EAPC)分别为0.11和0.55。糖尿病、缺血性心脏病(IHD)和中风的死亡人数最多(分别为1.66万人、1.35万人和84万人)。肝癌、慢性肾脏病(CKD)和胰腺癌的死亡率增长最快,EAPCs分别为1.90、1.69和1.34。IHD和卒中的死亡率负担下降,eapc分别为-0.13和-0.98。结论:30多年来,hfpg相关的非传染性疾病在全球范围内呈上升趋势。糖尿病、IHD和中风仍然是最主要的负担,而肝癌、CKD和胰腺癌的发病率上升最快。除了患有阿尔茨海默病和其他痴呆症以及失明和视力丧失(BVL)的人之外,男性的疾病负担高于女性。
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引用次数: 0
Pre-clinical studies show anti-diabetic effect of INSPARIN, a protein derived from the E4orf1 gene of a human adenovirus. 临床前研究表明,INSPARIN是一种从人腺病毒的E4orf1基因中提取的蛋白质,具有抗糖尿病作用。
IF 5.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM Pub Date : 2025-11-24 DOI: 10.1038/s41387-025-00406-6
Md Abu Bakkar Siddik, Zahra Feizy, Masoud Nateqi, Vijay Hegde, Nikhil V Dhurandhar

Background: Human adenovirus Ad36-derived protein, termed INSPARIN, up-regulates cellular glucose uptake through insulin-independent cell signaling. Transgenic or viral vector mediated delivery of INSPARIN exhibits significant anti-diabetic potential in mice. To translate these findings for clinical use, this preclinical study determined the short- and long-term effectiveness of nano-liposome-mediated delivery of INSPARIN to improve glucose metabolism in cell and animal models.

Methods: Void or INSPARIN Nanoparticles (NP) composed of soy-phosphatidylcholine were prepared freshly before use. Glucose uptake was measured in 3T3-L1, C2C12, and HepG2 cells following 72 h treatment with void or INSPARIN NP using a [³H]-2-deoxyglucose uptake assay. Male C57BL/6J mice fed a 45% high-fat diet received single or repeated subcutaneous injections of INSPARIN NP, followed by oral glucose tolerance tests, serum insulin, and HbA1c measurements. Biodistribution was assessed by DiD-labeled nanoparticle imaging, and long-term safety was evaluated by histopathology of major organs.

Results: INSPARIN NP upregulated glucose uptake in preadipocytes, hepatocytes, and myoblasts. In mice, INSPARIN NP delivered the drug to the liver when administered intravenously and to inguinal adipose tissue when administered subcutaneously. Single subcutaneous administration of INSPARIN NP promoted faster blood glucose clearance in a dose-dependent manner, but without leading to hypoglycemia. Daily subcutaneous administration of INSPARIN NP for seven weeks significantly reduced HbA1c levels despite continued high fat diet, and without any adverse effects on major organs studied.

Conclusions: These findings support suitability of nano-liposome mediated subcutaneous delivery of INSPARIN in clinical trials for treating diabetes.

背景:人腺病毒ad36衍生蛋白,称为INSPARIN,通过胰岛素不依赖的细胞信号传导上调细胞葡萄糖摄取。转基因或病毒载体介导的INSPARIN在小鼠中显示出显著的抗糖尿病潜力。为了将这些发现转化为临床应用,本临床前研究在细胞和动物模型中确定了纳米脂质体介导的INSPARIN递送改善葡萄糖代谢的短期和长期有效性。方法:使用前新鲜制备由大豆磷脂酰胆碱组成的空泡或INSPARIN纳米颗粒。采用[³h]-2-脱氧葡萄糖摄取法测定3T3-L1、C2C12和HepG2细胞在用void或INSPARIN NP处理72小时后的葡萄糖摄取。雄性C57BL/6J小鼠饲喂45%高脂饲料,单次或多次皮下注射INSPARIN NP,随后进行口服葡萄糖耐量试验、血清胰岛素和HbA1c测定。采用did标记的纳米颗粒成像评估生物分布,并通过主要器官的组织病理学评估长期安全性。结果:INSPARIN NP上调前脂肪细胞、肝细胞和成肌细胞的葡萄糖摄取。在小鼠中,INSPARIN NP在静脉给药时将药物输送到肝脏,在皮下给药时将药物输送到腹股沟脂肪组织。单次皮下给药INSPARIN NP促进了更快的血糖清除,且呈剂量依赖性,但不导致低血糖。在持续高脂肪饮食的情况下,每天皮下注射INSPARIN NP 7周,可显著降低HbA1c水平,且对研究的主要器官没有任何不良影响。结论:这些发现支持纳米脂质体介导的皮下给药INSPARIN在治疗糖尿病的临床试验中的适用性。
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引用次数: 0
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Nutrition & Diabetes
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