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.
{"title":"Association between assisted reproductive technology and gestational diabetes mellitus: the role of serum folate and triglycerides.","authors":"Bin Zhang, Sijie Xi, Runrun Hao, Zhaolong Zhan, Zhonghua Shi, Xiaosong Yuan","doi":"10.1038/s41387-026-00414-0","DOIUrl":"10.1038/s41387-026-00414-0","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13003119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372991","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}
Pub Date : 2026-03-02DOI: 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。
{"title":"Nutritional contents, nutritional quality and manufacturer of ready foods in China: a cross-sectional study of 2087 food products.","authors":"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","doi":"10.1038/s41387-026-00413-1","DOIUrl":"10.1038/s41387-026-00413-1","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12996493/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344752","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}
Pub Date : 2026-03-02DOI: 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.
{"title":"Heterogeneous effect of saxagliptin on glucose fluctuation and β-cell function in T1DM: a multicentre, randomised trial.","authors":"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","doi":"10.1038/s41387-026-00411-3","DOIUrl":"10.1038/s41387-026-00411-3","url":null,"abstract":"<p><strong>Background and aims: </strong>We aimed to explore whether saxagliptin, a dipeptidyl peptidase-IV inhibitor, could ameliorate glucose fluctuations and maintain β-cell function in T1DM.</p><p><strong>Methods and results: </strong>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-peptide<sub>max</sub> 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.</p><p><strong>Clinicaltrials: </strong>Gov number, NCT02307695.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":" ","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12987927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147344698","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}
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。
{"title":"The association between steatotic liver disease and chronic kidney disease: a meta-analysis and Mendelian randomization study highlighting metabolic comorbidities.","authors":"Xiang Ji, Jinguo Jiang, Yunyun Liu, Liuxin Li, Honghao Yang, Zheng Ma, Chenying Wang, Tingjing Zhang, Yuhong Zhao, Yashu Liu, Yang Xia","doi":"10.1038/s41387-026-00412-2","DOIUrl":"10.1038/s41387-026-00412-2","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"16 1","pages":""},"PeriodicalIF":5.2,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12929794/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276856","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}
Pub Date : 2026-01-22DOI: 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.
{"title":"The Beverage Quality Index and type 2 diabetes risk in women: a prospective analysis of the Mexican Teachers' Cohort.","authors":"Maria G Jacobo Cejudo, Adriana Monge, Neha Khandpur, Trudy Voortman, Dalia Stern, Johanna M Geleijnse","doi":"10.1038/s41387-026-00410-4","DOIUrl":"10.1038/s41387-026-00410-4","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":" ","pages":"3"},"PeriodicalIF":5.2,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12858936/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146030278","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}
Pub Date : 2026-01-03DOI: 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.
{"title":"Relationships between diabetes, vitamin D status, depression, and Hispanic ethnicity: a project FRONTIER study.","authors":"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","doi":"10.1038/s41387-025-00409-3","DOIUrl":"10.1038/s41387-025-00409-3","url":null,"abstract":"<p><strong>Background/objectives: </strong>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).</p><p><strong>Subjects/methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":" ","pages":"1"},"PeriodicalIF":5.2,"publicationDate":"2026-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12770327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145896615","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}
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.
{"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}
Pub Date : 2025-11-24DOI: 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.
{"title":"Umbelliferone preserves skin epidermal barrier integrity in diabetes-induced keratinocytes by regulating actin dynamics and suppressing ROS-mediated apoptosis.","authors":"Dong Yeon Kim, Young-Hee Kang, Min-Kyung Kang","doi":"10.1038/s41387-025-00407-5","DOIUrl":"10.1038/s41387-025-00407-5","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"51"},"PeriodicalIF":5.2,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12644754/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597071","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}
Pub Date : 2025-11-24DOI: 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).
{"title":"Global burden of 13 non-communicable diseases attributable to high fasting plasma glucose from the GBD 2021 study.","authors":"Junfeng Zhou, Zhengbin Yao, Shugen Xu, Yong Long, Zhao Zeng, Jiao Qin, Ning Ding, Yingjie Su","doi":"10.1038/s41387-025-00405-7","DOIUrl":"10.1038/s41387-025-00405-7","url":null,"abstract":"<p><strong>Background and objective: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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).</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"50"},"PeriodicalIF":5.2,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12644635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597073","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}
Pub Date : 2025-11-24DOI: 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.
{"title":"Pre-clinical studies show anti-diabetic effect of INSPARIN, a protein derived from the E4orf1 gene of a human adenovirus.","authors":"Md Abu Bakkar Siddik, Zahra Feizy, Masoud Nateqi, Vijay Hegde, Nikhil V Dhurandhar","doi":"10.1038/s41387-025-00406-6","DOIUrl":"10.1038/s41387-025-00406-6","url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>These findings support suitability of nano-liposome mediated subcutaneous delivery of INSPARIN in clinical trials for treating diabetes.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"15 1","pages":"52"},"PeriodicalIF":5.2,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12644549/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145597052","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}