Pub Date : 2024-08-15DOI: 10.1038/s41387-024-00325-y
Marta Carús-Cadavieco, Sandra González de la Fuente, Inés Berenguer López, Miguel A Serrano-Lope, Begoña Aguado, Francesc Guix, Ernest Palomer, Carlos G Dotti
Analyzing changes in gene expression within specific brain regions of individuals with Type 2 Diabetes (T2DM) who do not exhibit significant cognitive deficits can yield valuable insights into the mechanisms underlying the progression towards a more severe phenotype. In this study, transcriptomic analysis of the cortex and hippocampus of mice with long-term T2DM revealed alterations in the expression of 28 genes in the cerebral cortex and 15 genes in the hippocampus. Among these genes, six displayed consistent changes in both the cortex and hippocampus: Interferon regulatory factor 7 (Irf7), Hypoxia-inducible factor 3 alpha (Hif-3α), period circadian clock 2 (Per2), xanthine dehydrogenase (Xdh), and Transforming growth factor β-stimulated clone 22/TSC22 (Tsc22d3) were upregulated, while Claudin-5 (Cldn5) was downregulated. Confirmation of these changes was achieved through RT-qPCR. At the protein level, CLDN5 and IRF7 exhibited similar alterations, with CLDN5 being downregulated and IRF7 being upregulated. In addition, the hippocampus and cortex of the T2DM mice showed decreased levels of IκBα, implying the involvement of NF-κB pathways as well. Taken together, these results suggest that the weakening of the blood-brain barrier and an abnormal inflammatory response via the Interferon 1 and NF-κB pathways underlie cognitive impairment in individuals with long-standing T2DM.
{"title":"Loss of Cldn5 -and increase in Irf7-in the hippocampus and cerebral cortex of diabetic mice at the early symptomatic stage.","authors":"Marta Carús-Cadavieco, Sandra González de la Fuente, Inés Berenguer López, Miguel A Serrano-Lope, Begoña Aguado, Francesc Guix, Ernest Palomer, Carlos G Dotti","doi":"10.1038/s41387-024-00325-y","DOIUrl":"10.1038/s41387-024-00325-y","url":null,"abstract":"<p><p>Analyzing changes in gene expression within specific brain regions of individuals with Type 2 Diabetes (T2DM) who do not exhibit significant cognitive deficits can yield valuable insights into the mechanisms underlying the progression towards a more severe phenotype. In this study, transcriptomic analysis of the cortex and hippocampus of mice with long-term T2DM revealed alterations in the expression of 28 genes in the cerebral cortex and 15 genes in the hippocampus. Among these genes, six displayed consistent changes in both the cortex and hippocampus: Interferon regulatory factor 7 (Irf7), Hypoxia-inducible factor 3 alpha (Hif-3α), period circadian clock 2 (Per2), xanthine dehydrogenase (Xdh), and Transforming growth factor β-stimulated clone 22/TSC22 (Tsc22d3) were upregulated, while Claudin-5 (Cldn5) was downregulated. Confirmation of these changes was achieved through RT-qPCR. At the protein level, CLDN5 and IRF7 exhibited similar alterations, with CLDN5 being downregulated and IRF7 being upregulated. In addition, the hippocampus and cortex of the T2DM mice showed decreased levels of IκBα, implying the involvement of NF-κB pathways as well. Taken together, these results suggest that the weakening of the blood-brain barrier and an abnormal inflammatory response via the Interferon 1 and NF-κB pathways underlie cognitive impairment in individuals with long-standing T2DM.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"14 1","pages":"64"},"PeriodicalIF":4.6,"publicationDate":"2024-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11327336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141988475","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: With the fast pace of modern life, people have less time for meals, but few studies have examined the association between the habit of fast eating and metabolic diseases.
Objective: Combining the results of the current study and the prior ones, we aimed to investigate the possible relationship between fast eating and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD).
Methods: This is a sub-analysis of a multicenter cross-sectional study of 1965 participants investigated the association between fast eating and MASLD in Chinese. Fast eating was defined as meal time less than five minutes and participants were divided into three categories based on their self-reported frequency of fast eating: ≤1 time/month, ≤1 time/week and ≥2 times/week. We further conducted a literature search for available studies published before November, 2023 as well as a meta-analysis to investigate the association between fast eating and MASLD.
Results: The proportion of MASLD was 59.3%, 50.5%, and 46.2% in participants with fast eating ≥2 times/week, ≤1 time/week and ≤1 time/month, respectively (P for trend <0.001). The frequency of fast eating was independently associated with risk of MASLD after multiple adjustment for sex, age, demographics, smoking and drinking status, BMI and clinical metabolic parameters (OR, 1.29; 95%CI, 1.09-1.53). Participants who ate fast frequently (≥2 times/week) had 81% higher risk of MASLD (P = 0.011). A meta-analysis of five eligible studies confirmed that frequent fast eating was associated with increased risk of MASLD (pooled OR, 1.22; 95%CI, 1.07-1.39).
Conclusions: Frequent fast eating was associated with an increased risk of MASLD.
{"title":"Association between fast eating speed and metabolic dysfunction-associated steatotic liver disease: a multicenter cross-sectional study and meta-analysis.","authors":"Miao Zhang, Xiaoyang Sun, Xiaopeng Zhu, Lili Zheng, Yufang Bi, Qiang Li, Lirong Sun, Fusheng Di, Yushan Xu, Dalong Zhu, Yanyan Gao, Yuqian Bao, Yao Wang, Lanjie He, Chenmin Fan, Xin Gao, Jian Gao, Mingfeng Xia, Hua Bian","doi":"10.1038/s41387-024-00326-x","DOIUrl":"10.1038/s41387-024-00326-x","url":null,"abstract":"<p><strong>Background: </strong>With the fast pace of modern life, people have less time for meals, but few studies have examined the association between the habit of fast eating and metabolic diseases.</p><p><strong>Objective: </strong>Combining the results of the current study and the prior ones, we aimed to investigate the possible relationship between fast eating and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD).</p><p><strong>Methods: </strong>This is a sub-analysis of a multicenter cross-sectional study of 1965 participants investigated the association between fast eating and MASLD in Chinese. Fast eating was defined as meal time less than five minutes and participants were divided into three categories based on their self-reported frequency of fast eating: ≤1 time/month, ≤1 time/week and ≥2 times/week. We further conducted a literature search for available studies published before November, 2023 as well as a meta-analysis to investigate the association between fast eating and MASLD.</p><p><strong>Results: </strong>The proportion of MASLD was 59.3%, 50.5%, and 46.2% in participants with fast eating ≥2 times/week, ≤1 time/week and ≤1 time/month, respectively (P for trend <0.001). The frequency of fast eating was independently associated with risk of MASLD after multiple adjustment for sex, age, demographics, smoking and drinking status, BMI and clinical metabolic parameters (OR, 1.29; 95%CI, 1.09-1.53). Participants who ate fast frequently (≥2 times/week) had 81% higher risk of MASLD (P = 0.011). A meta-analysis of five eligible studies confirmed that frequent fast eating was associated with increased risk of MASLD (pooled OR, 1.22; 95%CI, 1.07-1.39).</p><p><strong>Conclusions: </strong>Frequent fast eating was associated with an increased risk of MASLD.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"14 1","pages":"61"},"PeriodicalIF":4.6,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324733/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982874","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 : 2024-08-14DOI: 10.1038/s41387-024-00316-z
Min-Jae Jang, Li-Juan Tan, Min Young Park, Sangah Shin, Jun-Mo Kim
Background & aim: Chronic kidney disease (CKD) is a heterogeneous disorder that affects the kidney structure and function. This study investigated the effect of the interaction between genetic factors and dietary pattern on kidney dysfunction in Korean adults.
Methods: Baseline data were obtained from the Ansan and Ansung Study of the Korean Genome and Epidemiology Study involving 8230 participants aged 40-69 years. Kidney dysfunction was defined as an estimated glomerular filtration rate < 90 mL/minute/1.73 m2. Genomic DNAs genotyped on the Affymetrix® Genome-Wide Human SNP array 5.0 were isolated from peripheral blood. A genome-wide association study using a generalized linear model was performed on 1,590,162 single-nucleotide polymorphisms (SNPs). To select significant SNPs, the threshold criterion was set at P-value < 5 × 10-8. Linkage disequilibrium clumping was performed based on the R2 value, and 94 SNPs had a significant effect. Participants were divided into two groups based on their generic risk score (GRS): the low-GR group had GRS > 0, while the high-GR group had GRS ≤ 0.
Results: Three distinct dietary patterns were extracted, namely, the "prudent pattern," "flour-based and animal food pattern," and "white rice pattern," to analyze the effect of dietary pattern on kidney function. In the "flour-based and animal food pattern," higher pattern scores were associated with a higher prevalence of kidney dysfunction in both the low and high GR groups (P for trend < 0.0001 in the low-, high-GR groups of model 1; 0.0050 and 0.0065 in the low-, high-GR groups of model 2, respectively).
Conclusions: The results highlight a significant association between the 'flour-based and animal food pattern' and higher kidney dysfunction prevalence in individuals with both low and high GR. These findings suggest that personalized nutritional interventions based on GR profiles may become the basis for presenting GR-based individual dietary patterns for kidney dysfunction.
背景和目的:慢性肾脏病(CKD)是一种影响肾脏结构和功能的异质性疾病。本研究调查了遗传因素和饮食模式之间的相互作用对韩国成年人肾功能障碍的影响:基线数据来自韩国基因组与流行病学研究的安山和安城研究,共有 8230 名参与者,年龄在 40-69 岁之间。肾功能障碍的定义是估计肾小球滤过率为 2。从外周血中分离出在 Affymetrix® Genome-Wide Human SNP array 5.0 上进行基因分型的基因组 DNA。利用广义线性模型对 1,590,162 个单核苷酸多态性(SNPs)进行了全基因组关联研究。为了选择有意义的 SNPs,阈值标准设定为 P 值 -8。根据 R2 值进行了连锁不平衡聚类,结果有 94 个 SNPs 有显著影响。根据通用风险评分(GRS)将参与者分为两组:低GR组的GRS>0,而高GR组的GRS≤0:提取了三种不同的膳食模式,即 "谨慎模式"、"面粉和动物性食物模式 "和 "白米饭模式",以分析膳食模式对肾功能的影响。在 "以面粉和动物性食物为主的膳食模式 "中,较高的模式得分与低GR组和高GR组较高的肾功能障碍患病率相关(P为趋势性结论):研究结果表明,"以面粉和动物性食物为主的食物模式 "与低GR和高GR人群中较高的肾功能障碍患病率之间存在明显关联。这些研究结果表明,基于 GR 图谱的个性化营养干预可能成为针对肾功能障碍提出基于 GR 的个人饮食模式的基础。
{"title":"Identification of interactions between genetic risk scores and dietary patterns for personalized prevention of kidney dysfunction in a population-based cohort.","authors":"Min-Jae Jang, Li-Juan Tan, Min Young Park, Sangah Shin, Jun-Mo Kim","doi":"10.1038/s41387-024-00316-z","DOIUrl":"10.1038/s41387-024-00316-z","url":null,"abstract":"<p><strong>Background & aim: </strong>Chronic kidney disease (CKD) is a heterogeneous disorder that affects the kidney structure and function. This study investigated the effect of the interaction between genetic factors and dietary pattern on kidney dysfunction in Korean adults.</p><p><strong>Methods: </strong>Baseline data were obtained from the Ansan and Ansung Study of the Korean Genome and Epidemiology Study involving 8230 participants aged 40-69 years. Kidney dysfunction was defined as an estimated glomerular filtration rate < 90 mL/minute/1.73 m<sup>2</sup>. Genomic DNAs genotyped on the Affymetrix® Genome-Wide Human SNP array 5.0 were isolated from peripheral blood. A genome-wide association study using a generalized linear model was performed on 1,590,162 single-nucleotide polymorphisms (SNPs). To select significant SNPs, the threshold criterion was set at P-value < 5 × 10<sup>-</sup><sup>8</sup>. Linkage disequilibrium clumping was performed based on the R<sup>2</sup> value, and 94 SNPs had a significant effect. Participants were divided into two groups based on their generic risk score (GRS): the low-GR group had GRS > 0, while the high-GR group had GRS ≤ 0.</p><p><strong>Results: </strong>Three distinct dietary patterns were extracted, namely, the \"prudent pattern,\" \"flour-based and animal food pattern,\" and \"white rice pattern,\" to analyze the effect of dietary pattern on kidney function. In the \"flour-based and animal food pattern,\" higher pattern scores were associated with a higher prevalence of kidney dysfunction in both the low and high GR groups (P for trend < 0.0001 in the low-, high-GR groups of model 1; 0.0050 and 0.0065 in the low-, high-GR groups of model 2, respectively).</p><p><strong>Conclusions: </strong>The results highlight a significant association between the 'flour-based and animal food pattern' and higher kidney dysfunction prevalence in individuals with both low and high GR. These findings suggest that personalized nutritional interventions based on GR profiles may become the basis for presenting GR-based individual dietary patterns for kidney dysfunction.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"14 1","pages":"62"},"PeriodicalIF":4.6,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11325018/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982875","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 : 2024-08-14DOI: 10.1038/s41387-024-00324-z
HuiZhi Shao, Xiang Liu, DaShuai Zong, QingJun Song
Background: Diabetes, as a significant disease affecting public health, requires early detection for effective management and intervention. However, imbalanced datasets pose a challenge to accurate diabetes prediction. This imbalance often results in models performing poorly in predicting minority classes, affecting overall diagnostic performance.
Objectives: To address this issue, this study employs a combination of Synthetic Minority Over-sampling Technique (SMOTE) and Random Under-Sampling (RUS) for data balancing and uses Optuna for hyperparameter optimization of machine learning models. This approach aims to fill the gap in current research concerning data balancing and model optimization, thereby improving prediction accuracy and computational efficiency.
Methods: First, the study uses SMOTE and RUS methods to process the imbalanced diabetes dataset, balancing the data distribution. Then, Optuna is utilized to optimize the hyperparameters of the LightGBM model to enhance its performance. During the experiment, the effectiveness of the proposed methods is evaluated by comparing the training results of the dataset before and after balancing.
Results: The experimental results show that the enhanced LightGBM-Optuna model improves the accuracy from 97.07% to 97.11%, and the precision from 97.17% to 98.99%. The time required for a single search is only 2.5 seconds. These results demonstrate the superiority of the proposed method in handling imbalanced datasets and optimizing model performance.
Conclusions: The study indicates that combining SMOTE and RUS data balancing algorithms with Optuna for hyperparameter optimization can effectively enhance machine learning models, especially in dealing with imbalanced datasets for diabetes prediction.
{"title":"Optimization of diabetes prediction methods based on combinatorial balancing algorithm.","authors":"HuiZhi Shao, Xiang Liu, DaShuai Zong, QingJun Song","doi":"10.1038/s41387-024-00324-z","DOIUrl":"10.1038/s41387-024-00324-z","url":null,"abstract":"<p><strong>Background: </strong>Diabetes, as a significant disease affecting public health, requires early detection for effective management and intervention. However, imbalanced datasets pose a challenge to accurate diabetes prediction. This imbalance often results in models performing poorly in predicting minority classes, affecting overall diagnostic performance.</p><p><strong>Objectives: </strong>To address this issue, this study employs a combination of Synthetic Minority Over-sampling Technique (SMOTE) and Random Under-Sampling (RUS) for data balancing and uses Optuna for hyperparameter optimization of machine learning models. This approach aims to fill the gap in current research concerning data balancing and model optimization, thereby improving prediction accuracy and computational efficiency.</p><p><strong>Methods: </strong>First, the study uses SMOTE and RUS methods to process the imbalanced diabetes dataset, balancing the data distribution. Then, Optuna is utilized to optimize the hyperparameters of the LightGBM model to enhance its performance. During the experiment, the effectiveness of the proposed methods is evaluated by comparing the training results of the dataset before and after balancing.</p><p><strong>Results: </strong>The experimental results show that the enhanced LightGBM-Optuna model improves the accuracy from 97.07% to 97.11%, and the precision from 97.17% to 98.99%. The time required for a single search is only 2.5 seconds. These results demonstrate the superiority of the proposed method in handling imbalanced datasets and optimizing model performance.</p><p><strong>Conclusions: </strong>The study indicates that combining SMOTE and RUS data balancing algorithms with Optuna for hyperparameter optimization can effectively enhance machine learning models, especially in dealing with imbalanced datasets for diabetes prediction.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"14 1","pages":"63"},"PeriodicalIF":4.6,"publicationDate":"2024-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11324958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141982876","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: Type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) are prevalent metabolic disorders with overlapping pathophysiological mechanisms. A comprehensive understanding of the shared molecular pathways involved in these conditions can advance the development of effective therapeutic interventions.
Methods: We used two datasets sourced from the Gene Expression Omnibus (GEO) database to identify common differentially expressed genes (DEGs) between T2D and NAFLD. Subsequently, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to identify the enriched biological processes and signaling pathways. In addition, we performed a protein-protein interaction (PPI) network analysis to identify hub genes with pivotal roles. To validate our findings, we established a type 2 diabetic mouse model with NAFLD.
Results: Our analysis identified 53 DEGs shared between T2D and NAFLD. Enrichment analysis revealed their involvement in signal transduction, transcriptional regulation, and cell proliferation as well as in the ferroptosis signaling pathways. PPI network analysis identified ten hub genes, namely CD44, CASP3, FYN, KLF4, HNRNPM, HNRNPU, FUBP1, RUNX1, NOTCH3, and ANXA2. We validated the differential expression of FYN, HNRNPU, and FUBP1 in liver tissues of a type 2 diabetic mouse model with NAFLD.
Conclusions: Our study offers valuable insights into the shared molecular mechanisms underlying T2D and NAFLD. The identified hub genes and pathways present promising prospects as therapeutic targets to address these prevalent metabolic disorders.
{"title":"Pathogenic gene connections in type 2 diabetes and non-alcoholic fatty liver disease: a bioinformatics analysis and mouse model investigations experiments.","authors":"Chao Chen, Kunhuan Yang, Yuhan Zhang, Meiqi Lu, Xiaoyan Zhao, Zheng Wan","doi":"10.1038/s41387-024-00323-0","DOIUrl":"10.1038/s41387-024-00323-0","url":null,"abstract":"<p><strong>Background: </strong>Type 2 diabetes (T2D) and non-alcoholic fatty liver disease (NAFLD) are prevalent metabolic disorders with overlapping pathophysiological mechanisms. A comprehensive understanding of the shared molecular pathways involved in these conditions can advance the development of effective therapeutic interventions.</p><p><strong>Methods: </strong>We used two datasets sourced from the Gene Expression Omnibus (GEO) database to identify common differentially expressed genes (DEGs) between T2D and NAFLD. Subsequently, we conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to identify the enriched biological processes and signaling pathways. In addition, we performed a protein-protein interaction (PPI) network analysis to identify hub genes with pivotal roles. To validate our findings, we established a type 2 diabetic mouse model with NAFLD.</p><p><strong>Results: </strong>Our analysis identified 53 DEGs shared between T2D and NAFLD. Enrichment analysis revealed their involvement in signal transduction, transcriptional regulation, and cell proliferation as well as in the ferroptosis signaling pathways. PPI network analysis identified ten hub genes, namely CD44, CASP3, FYN, KLF4, HNRNPM, HNRNPU, FUBP1, RUNX1, NOTCH3, and ANXA2. We validated the differential expression of FYN, HNRNPU, and FUBP1 in liver tissues of a type 2 diabetic mouse model with NAFLD.</p><p><strong>Conclusions: </strong>Our study offers valuable insights into the shared molecular mechanisms underlying T2D and NAFLD. The identified hub genes and pathways present promising prospects as therapeutic targets to address these prevalent metabolic disorders.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"14 1","pages":"60"},"PeriodicalIF":4.6,"publicationDate":"2024-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11303809/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141897909","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 : 2024-08-03DOI: 10.1038/s41387-024-00321-2
Gang Ti, Yuan He, Youde Xiao, Jiyuan Yan, Rong Ding, Pengfei Cheng, Wei Wu, Dawei Ye, Jinxi Wang, Lili Li
Background: Due to the essential role of calcium in vital biological functions, diet low in calcium (DLC) is associated with various diseases. However, there is a lack of study about the current prevalence and health burden due to DLC using reliable data sources.
Methods: We used data from the Global Burden of Disease study 2019 (GBD 2019) to estimate the prevalence and health burden of DLC in 204 countries from 1990 to 2019, by age, sex, and sociodemographic index (SDI). The estimates were produced in DisMod-MR 2.1, a Bayesian meta-regression tool. Summary exposure value (SEV) was used to show the prevalence of DLC, while diseases adjusted life year (DALY) was used to represent the disease burden. The disease burden was estimated for DLC-induced colorectal cancer. Spearman Rank Order correlation was used for correlation analysis, and estimated annual percentage (EAPC) was used to reflect the temporal trends.
Results: From 1990 to 2019, the global prevalence of DLC decreased (EAPC of SEV, -0.47; 95% CI, -0.5 to -0.43), but have increased in Oceania region and in many countries, such as United Arab Emirates, New Zealand, Japan, and France. The global DALYs associated with low in calcium were estimated to be 3.14 million (95% uncertainty interval (UI), 2.25-4.26 million) in 2019, with an age standardized rate of 38.2 (95% UI, 27.2-51.8) per 100,000. Unlike the prevalence, the global age standardized DALY rates has remained unchanged (EAPC, -0.03; 95% CI, -0.12 to 0.07), but has increased in over 80 of the 204 countries, located mainly in Asia, Africa, and South America. In all years and regions, the age standardized SEV and DALY rates were higher in male people than that in female people. The prevalence (rho = -0.823; P < 0.001) and disease burden (rho = -0.433; P < 0.001) associated with diet in low calcium were strongly correlated to SDI. The prevalence decreased with age, but the DALY rates increased with age and peaked at about 90 years. The prevalence of DLC has decreased worldwide and in most countries, but the disease burden of DLC induced colorectal cancer has increased in over 40% of countries worldwide.
Conclusion: Countries with low sociodemographic level and male people are more likely to experience the risk of DLC and related disease burden. Related measures in improve dietary calcium intake are in need to address diet in low calcium related health problems.
{"title":"Global prevalence of diet low in calcium and the disease burden: results from the Global Burden of Disease Study 2019.","authors":"Gang Ti, Yuan He, Youde Xiao, Jiyuan Yan, Rong Ding, Pengfei Cheng, Wei Wu, Dawei Ye, Jinxi Wang, Lili Li","doi":"10.1038/s41387-024-00321-2","DOIUrl":"10.1038/s41387-024-00321-2","url":null,"abstract":"<p><strong>Background: </strong>Due to the essential role of calcium in vital biological functions, diet low in calcium (DLC) is associated with various diseases. However, there is a lack of study about the current prevalence and health burden due to DLC using reliable data sources.</p><p><strong>Methods: </strong>We used data from the Global Burden of Disease study 2019 (GBD 2019) to estimate the prevalence and health burden of DLC in 204 countries from 1990 to 2019, by age, sex, and sociodemographic index (SDI). The estimates were produced in DisMod-MR 2.1, a Bayesian meta-regression tool. Summary exposure value (SEV) was used to show the prevalence of DLC, while diseases adjusted life year (DALY) was used to represent the disease burden. The disease burden was estimated for DLC-induced colorectal cancer. Spearman Rank Order correlation was used for correlation analysis, and estimated annual percentage (EAPC) was used to reflect the temporal trends.</p><p><strong>Results: </strong>From 1990 to 2019, the global prevalence of DLC decreased (EAPC of SEV, -0.47; 95% CI, -0.5 to -0.43), but have increased in Oceania region and in many countries, such as United Arab Emirates, New Zealand, Japan, and France. The global DALYs associated with low in calcium were estimated to be 3.14 million (95% uncertainty interval (UI), 2.25-4.26 million) in 2019, with an age standardized rate of 38.2 (95% UI, 27.2-51.8) per 100,000. Unlike the prevalence, the global age standardized DALY rates has remained unchanged (EAPC, -0.03; 95% CI, -0.12 to 0.07), but has increased in over 80 of the 204 countries, located mainly in Asia, Africa, and South America. In all years and regions, the age standardized SEV and DALY rates were higher in male people than that in female people. The prevalence (rho = -0.823; P < 0.001) and disease burden (rho = -0.433; P < 0.001) associated with diet in low calcium were strongly correlated to SDI. The prevalence decreased with age, but the DALY rates increased with age and peaked at about 90 years. The prevalence of DLC has decreased worldwide and in most countries, but the disease burden of DLC induced colorectal cancer has increased in over 40% of countries worldwide.</p><p><strong>Conclusion: </strong>Countries with low sociodemographic level and male people are more likely to experience the risk of DLC and related disease burden. Related measures in improve dietary calcium intake are in need to address diet in low calcium related health problems.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"14 1","pages":"59"},"PeriodicalIF":4.6,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297965/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889875","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 : 2024-08-02DOI: 10.1038/s41387-024-00319-w
Francesco Antonio Mazzotta, Lorenzo Lucaccini Paoli, Alessandro Rizzi, Linda Tartaglione, Maria Laura Leo, Valentina Popolla, Annarita Barberio, Luca Viti, Mauro Di Leo, Alfredo Pontecorvi, Dario Pitocco
The development of advanced diabetes technology has permitted persons with type 1 diabetes mellitus to improve metabolic control significantly, particularly with the development of advanced hybrid closed-loop systems which have improved the quality of life by reducing hypoglycemia, decreasing macroangiopathy and microangiopathy-related complications, ameliorating HbA1c and improving glycemic variability. Despite the progression made over the past few decades, there is still significant margin for improvement to be made in terms of attaining appropriate metabolic control. Various factors are responsible for poor glycemic control including inappropriate carbohydrate counting, repeated bouts of hypoglycemia, hypoglycemia unawareness, cutaneous manifestations due to localized insulin use and prolonged use of diabetes technology, psychosocial comorbidities such as eating disorders or 'diabulimia', the coexistence of insulin resistance among people with type 1 diabetes and the inability to mirror physiological endogenous pancreatic insulin secretion appropriately. Hence, the aim of this review is to highlight and overcome the barriers in attaining appropriate metabolic control among people with type 1 diabetes by driving research into adjunctive treatment for coexistent insulin resistance and developing new advanced diabetic technologies to preserve β cell function and mirror as much as possible endogenous pancreatic functions.
{"title":"Unmet needs in the treatment of type 1 diabetes: why is it so difficult to achieve an improvement in metabolic control?","authors":"Francesco Antonio Mazzotta, Lorenzo Lucaccini Paoli, Alessandro Rizzi, Linda Tartaglione, Maria Laura Leo, Valentina Popolla, Annarita Barberio, Luca Viti, Mauro Di Leo, Alfredo Pontecorvi, Dario Pitocco","doi":"10.1038/s41387-024-00319-w","DOIUrl":"10.1038/s41387-024-00319-w","url":null,"abstract":"<p><p>The development of advanced diabetes technology has permitted persons with type 1 diabetes mellitus to improve metabolic control significantly, particularly with the development of advanced hybrid closed-loop systems which have improved the quality of life by reducing hypoglycemia, decreasing macroangiopathy and microangiopathy-related complications, ameliorating HbA1c and improving glycemic variability. Despite the progression made over the past few decades, there is still significant margin for improvement to be made in terms of attaining appropriate metabolic control. Various factors are responsible for poor glycemic control including inappropriate carbohydrate counting, repeated bouts of hypoglycemia, hypoglycemia unawareness, cutaneous manifestations due to localized insulin use and prolonged use of diabetes technology, psychosocial comorbidities such as eating disorders or 'diabulimia', the coexistence of insulin resistance among people with type 1 diabetes and the inability to mirror physiological endogenous pancreatic insulin secretion appropriately. Hence, the aim of this review is to highlight and overcome the barriers in attaining appropriate metabolic control among people with type 1 diabetes by driving research into adjunctive treatment for coexistent insulin resistance and developing new advanced diabetic technologies to preserve β cell function and mirror as much as possible endogenous pancreatic functions.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"14 1","pages":"58"},"PeriodicalIF":4.6,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297181/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879207","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 : 2024-08-02DOI: 10.1038/s41387-024-00322-1
Immacolata Cristina Nettore, Giuseppe Palatucci, Paola Ungaro, Giuseppe Scidà, Alessandra Corrado, Rosa De Vito, Marilena Vitale, Anna Maria Rivieccio, Giovanni Annuzzi, Lutgarda Bozzetto, Annamaria Colao, Paolo Emidio Macchia
Background/objectives: Adherence to dietary recommendations is a critical component in the management of type 1 diabetes (T1D). Taste and flavor significantly influence food choices. The aim of this study was to investigate taste sensitivity and flavor recognition ability in adults with T1D compared to healthy individuals.
Subjects/methods: Seventy-two people with T1D and 72 matched healthy controls participated in the study. Participants underwent the gustometry test for sweet, sour, salty, and bitter tastes and the flavor test, which consisted of oral administration of aqueous aromatic solutions identifying 21 different compounds.
Results: Participants with T1D had significantly lower flavor scores and gustometry scores than controls (p < 0.0001 and p = 0.0063, respectively). T1D individuals showed a lower perception of sour, bitter and salty tastes than controls, while the perception of sweet taste was similar. The sex differences and age-related decline in flavor perception observed in controls were not present in the participants with T1D. Neither BMI nor disease-related parameters such as fasting blood glucose on the day of the study, glycosylated hemoglobin, age at onset of diabetes, duration of diabetes, or type of insulin treatment (insulin pump or multiple daily injections) correlated with flavor and taste perception in the T1D participants.
Conclusions: Flavor and taste perception are impaired in adults with T1D, potentially affecting dietary adherence and food choices. This highlights the need for further research into the mechanisms underlying sensory changes in T1D and emphasizes the importance of targeted dietary interventions to improve health outcomes and quality of life in this population.
{"title":"Flavor and taste recognition impairments in people with type 1 diabetes.","authors":"Immacolata Cristina Nettore, Giuseppe Palatucci, Paola Ungaro, Giuseppe Scidà, Alessandra Corrado, Rosa De Vito, Marilena Vitale, Anna Maria Rivieccio, Giovanni Annuzzi, Lutgarda Bozzetto, Annamaria Colao, Paolo Emidio Macchia","doi":"10.1038/s41387-024-00322-1","DOIUrl":"10.1038/s41387-024-00322-1","url":null,"abstract":"<p><strong>Background/objectives: </strong>Adherence to dietary recommendations is a critical component in the management of type 1 diabetes (T1D). Taste and flavor significantly influence food choices. The aim of this study was to investigate taste sensitivity and flavor recognition ability in adults with T1D compared to healthy individuals.</p><p><strong>Subjects/methods: </strong>Seventy-two people with T1D and 72 matched healthy controls participated in the study. Participants underwent the gustometry test for sweet, sour, salty, and bitter tastes and the flavor test, which consisted of oral administration of aqueous aromatic solutions identifying 21 different compounds.</p><p><strong>Results: </strong>Participants with T1D had significantly lower flavor scores and gustometry scores than controls (p < 0.0001 and p = 0.0063, respectively). T1D individuals showed a lower perception of sour, bitter and salty tastes than controls, while the perception of sweet taste was similar. The sex differences and age-related decline in flavor perception observed in controls were not present in the participants with T1D. Neither BMI nor disease-related parameters such as fasting blood glucose on the day of the study, glycosylated hemoglobin, age at onset of diabetes, duration of diabetes, or type of insulin treatment (insulin pump or multiple daily injections) correlated with flavor and taste perception in the T1D participants.</p><p><strong>Conclusions: </strong>Flavor and taste perception are impaired in adults with T1D, potentially affecting dietary adherence and food choices. This highlights the need for further research into the mechanisms underlying sensory changes in T1D and emphasizes the importance of targeted dietary interventions to improve health outcomes and quality of life in this population.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"14 1","pages":"57"},"PeriodicalIF":4.6,"publicationDate":"2024-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11297142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141879206","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 : 2024-07-23DOI: 10.1038/s41387-024-00313-2
Saeede Jafari Nasab, Matin Ghanavati, Cain C T Clark, Maryam Nasirian
Background and aim: Gestational diabetes mellitus (GDM) is one of the most prevalent disorders occurring during pregnancy, which confers significant risk of short and long-term adverse outcomes in both mothers and offspring. Recently, more attention has been paid to the association of pre-pregnancy and early pregnancy healthy dietary patterns, such as Mediterranean dietary pattern with GDM. However, there is a lack of systematic review and meta-analysis summarizing findings in this regard. Hence, we sought to assess the association of MedDiet and GDM in observational studies by performing a systematic review and meta-analysis.
Methods: A comprehensive systematic literature search of observational studies was conducted via PubMed, Scopus, and Google Scholar, up to August 2023. Studies were included in our review if they evaluated the association of MedDiet and GDM, following an observational study design.
Results: Ten studies were included in this study. Combining effect sizes, we found that adherence to MedDiet was inversely associated with GDM risk (OR = 0.64; CI: 0.52-0.78); implying that higher adherence to the MedDiet could reduce the risk of GDM by about 36%. Stratification by the geographic area, Mediterranean countries, time of dietary assessment and study design, showed a consistent significant association between MedDiet and GDM.
Conclusion: We conclude that adhering to diets resembling MedDiet, before or in early pregnancy, could be associated with lower risks or odds of GDM.
{"title":"Adherence to Mediterranean dietary pattern and the risk of gestational diabetes mellitus: a systematic review and meta-analysis of observational studies.","authors":"Saeede Jafari Nasab, Matin Ghanavati, Cain C T Clark, Maryam Nasirian","doi":"10.1038/s41387-024-00313-2","DOIUrl":"10.1038/s41387-024-00313-2","url":null,"abstract":"<p><strong>Background and aim: </strong>Gestational diabetes mellitus (GDM) is one of the most prevalent disorders occurring during pregnancy, which confers significant risk of short and long-term adverse outcomes in both mothers and offspring. Recently, more attention has been paid to the association of pre-pregnancy and early pregnancy healthy dietary patterns, such as Mediterranean dietary pattern with GDM. However, there is a lack of systematic review and meta-analysis summarizing findings in this regard. Hence, we sought to assess the association of MedDiet and GDM in observational studies by performing a systematic review and meta-analysis.</p><p><strong>Methods: </strong>A comprehensive systematic literature search of observational studies was conducted via PubMed, Scopus, and Google Scholar, up to August 2023. Studies were included in our review if they evaluated the association of MedDiet and GDM, following an observational study design.</p><p><strong>Results: </strong>Ten studies were included in this study. Combining effect sizes, we found that adherence to MedDiet was inversely associated with GDM risk (OR = 0.64; CI: 0.52-0.78); implying that higher adherence to the MedDiet could reduce the risk of GDM by about 36%. Stratification by the geographic area, Mediterranean countries, time of dietary assessment and study design, showed a consistent significant association between MedDiet and GDM.</p><p><strong>Conclusion: </strong>We conclude that adhering to diets resembling MedDiet, before or in early pregnancy, could be associated with lower risks or odds of GDM.</p>","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"14 1","pages":"55"},"PeriodicalIF":4.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11263544/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748709","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 : 2024-07-23DOI: 10.1038/s41387-024-00299-x
Yi-Shang Yan, Jia-Ying Mo, Yu-Tong Huang, Hong Zhu, Hai-Yan Wu, Zhong-Liang Lin, Rui Liu, Xuan-Qi Liu, Ping-Ping Lv, Chun Feng, Jian-Zhong Sheng, Min Jin, He-Feng Huang
<p><strong>Background: </strong>Maternal diabetes mellitus can influence the development of offspring. Gestational diabetes mellitus (GDM) creates a short-term intrauterine hyperglycaemic environment in offspring, leading to glucose intolerance in later life, but the long-term effects and specific mechanism involved in skeletal muscle dysfunction in offspring remain to be clarified.</p><p><strong>Methods: </strong>Pregnant mice were divided into two groups: The GDM group was intraperitoneally injected with 100 mg/kg streptozotocin on gestational days (GDs) 6.5 and 12.5, while the control (CTR) group was treated with vehicle buffer. Only pregnant mice whose random blood glucose level was higher than 16.8 mmol/L beginning on GD13.5 were regarded as the GDM group. The growth of the offspring was monitored, and the glucose tolerance test was performed at different time points. Body composition analysis and immunohistochemical methods were used to evaluate the development of lean mass at 8 weeks. The exercise capacity and grip strength of the male mouse offspring were assessed at the same period. Transmission electron microscopy was used to observe the morphology inside skeletal muscle at 8 weeks and as a foetus. The genes and proteins associated with mitochondrial biogenesis and oxidative metabolism were investigated. We also coanalyzed RNA sequencing and proteomics data to explore the underlying mechanism. Chromatin immunoprecipitation and bisulfite-converted DNA methylation detection were performed to evaluate this phenomenon.</p><p><strong>Results: </strong>Short-term intrauterine hyperglycaemia inhibited the growth and reduced the lean mass of male offspring, leading to decreased endurance exercise capacity. The myofiber composition of the tibialis anterior muscle of GDM male offspring became more glycolytic and less oxidative. The morphology and function of mitochondria in the skeletal muscle of GDM male offspring were destroyed, and coanalysis of RNA sequencing and proteomics of foetal skeletal muscle showed that mitochondrial elements and lipid oxidation were consistently impaired. In vivo and in vitro myoblast experiments also demonstrated that high glucose concentrations impeded mitochondrial organisation and function. Importantly, the transcription of genes associated with mitochondrial biogenesis and oxidative metabolism decreased at 8 weeks and during the foetal period. We predicted Ppargc1α as a key upstream regulator with the help of IPA software. The proteins and mRNA levels of Ppargc1α in the skeletal muscle of GDM male offspring were decreased as a foetus (CTR vs. GDM, 1.004 vs. 0.665, p = 0.002), at 6 weeks (1.018 vs. 0.511, p = 0.023) and 8 weeks (1.006 vs. 0.596, p = 0.018). In addition, CREB phosphorylation was inhibited in GDM group, with fewer activated pCREB proteins binding to the CRE element of Ppargc1α (1.042 vs. 0.681, p = 0.037), Pck1 (1.091 vs. 0.432, p = 0.014) and G6pc (1.118 vs. 0.472, p = 0.027), resulting in their d
背景:母体糖尿病会影响后代的发育。妊娠糖尿病(GDM)会给后代造成短期的宫内高血糖环境,导致后代葡萄糖不耐受,但其对后代骨骼肌功能障碍的长期影响和具体机制仍有待明确:方法:将妊娠小鼠分为两组:方法:将妊娠小鼠分为两组:GDM 组在妊娠 6.5 天和 12.5 天腹腔注射 100 毫克/千克链脲佐菌素,对照(CTR)组使用缓冲液。只有从妊娠日 13.5 开始随机血糖水平高于 16.8 mmol/L 的妊娠小鼠才被视为 GDM 组。监测后代的生长情况,并在不同时间点进行葡萄糖耐量试验。采用身体成分分析和免疫组化方法评估 8 周时瘦体重的发育情况。同期还评估了雄性小鼠后代的运动能力和握力。透射电子显微镜用于观察小鼠8周时和胎儿时期骨骼肌内部的形态。我们还研究了与线粒体生物生成和氧化代谢相关的基因和蛋白质。我们还共同分析了 RNA 测序和蛋白质组学数据,以探索其潜在机制。我们还进行了染色质免疫共沉淀和亚硫酸氢盐转化 DNA 甲基化检测,以评估这一现象:结果:短期宫内高血糖抑制了雄性后代的生长并降低了其瘦体重,导致其耐力运动能力下降。GDM雄性后代胫骨前肌的肌纤维组成中,糖酵解成分增多,氧化成分减少。GDM雄性后代骨骼肌中线粒体的形态和功能遭到破坏,胎儿骨骼肌的RNA测序和蛋白质组学共同分析表明,线粒体元素和脂质氧化持续受损。体内和体外成肌细胞实验也表明,高浓度葡萄糖会阻碍线粒体的组织和功能。重要的是,与线粒体生物发生和氧化代谢相关的基因转录在 8 周时和胎儿期减少。我们借助 IPA 软件预测 Ppargc1α 是一个关键的上游调节因子。GDM雄性后代骨骼肌中的Ppargc1α蛋白和mRNA水平在胎儿期(CTR vs. GDM, 1.004 vs. 0.665, p = 0.002)、6周(1.018 vs. 0.511, p = 0.023)和8周(1.006 vs. 0.596, p = 0.018)均有所下降。此外,GDM 组的 CREB 磷酸化受到抑制,与 Ppargc1α (1.042 vs. 0.681, p = 0.037)、Pck1 (1.091 vs. 0.432, p = 0.014) 和 G6pc (1.118 vs. 0.472, p = 0.027) 的 CRE 元结合的活化 pCREB 蛋白减少,导致其转录减少。有趣的是,我们发现肌肉疏松症和线粒体功能障碍甚至会遗传给下一代:结论:短期宫内高血糖会显著降低男性后代 8 周时的瘦体重,导致运动耐力下降和代谢紊乱。在他们中间还观察到骨骼肌线粒体的组织和功能紊乱。胎儿暴露于高血糖状态会降低磷酸化 CREB 的比率,减少 Ppargc1α 的转录,从而抑制线粒体生物生成和氧化代谢下游基因的转录。在 F2 代中也观察到异常线粒体,这可能是通过异常配子传播的。
{"title":"Intrauterine hyperglycaemia during late gestation caused mitochondrial dysfunction in skeletal muscle of male offspring through CREB/PGC1A signaling.","authors":"Yi-Shang Yan, Jia-Ying Mo, Yu-Tong Huang, Hong Zhu, Hai-Yan Wu, Zhong-Liang Lin, Rui Liu, Xuan-Qi Liu, Ping-Ping Lv, Chun Feng, Jian-Zhong Sheng, Min Jin, He-Feng Huang","doi":"10.1038/s41387-024-00299-x","DOIUrl":"10.1038/s41387-024-00299-x","url":null,"abstract":"<p><strong>Background: </strong>Maternal diabetes mellitus can influence the development of offspring. Gestational diabetes mellitus (GDM) creates a short-term intrauterine hyperglycaemic environment in offspring, leading to glucose intolerance in later life, but the long-term effects and specific mechanism involved in skeletal muscle dysfunction in offspring remain to be clarified.</p><p><strong>Methods: </strong>Pregnant mice were divided into two groups: The GDM group was intraperitoneally injected with 100 mg/kg streptozotocin on gestational days (GDs) 6.5 and 12.5, while the control (CTR) group was treated with vehicle buffer. Only pregnant mice whose random blood glucose level was higher than 16.8 mmol/L beginning on GD13.5 were regarded as the GDM group. The growth of the offspring was monitored, and the glucose tolerance test was performed at different time points. Body composition analysis and immunohistochemical methods were used to evaluate the development of lean mass at 8 weeks. The exercise capacity and grip strength of the male mouse offspring were assessed at the same period. Transmission electron microscopy was used to observe the morphology inside skeletal muscle at 8 weeks and as a foetus. The genes and proteins associated with mitochondrial biogenesis and oxidative metabolism were investigated. We also coanalyzed RNA sequencing and proteomics data to explore the underlying mechanism. Chromatin immunoprecipitation and bisulfite-converted DNA methylation detection were performed to evaluate this phenomenon.</p><p><strong>Results: </strong>Short-term intrauterine hyperglycaemia inhibited the growth and reduced the lean mass of male offspring, leading to decreased endurance exercise capacity. The myofiber composition of the tibialis anterior muscle of GDM male offspring became more glycolytic and less oxidative. The morphology and function of mitochondria in the skeletal muscle of GDM male offspring were destroyed, and coanalysis of RNA sequencing and proteomics of foetal skeletal muscle showed that mitochondrial elements and lipid oxidation were consistently impaired. In vivo and in vitro myoblast experiments also demonstrated that high glucose concentrations impeded mitochondrial organisation and function. Importantly, the transcription of genes associated with mitochondrial biogenesis and oxidative metabolism decreased at 8 weeks and during the foetal period. We predicted Ppargc1α as a key upstream regulator with the help of IPA software. The proteins and mRNA levels of Ppargc1α in the skeletal muscle of GDM male offspring were decreased as a foetus (CTR vs. GDM, 1.004 vs. 0.665, p = 0.002), at 6 weeks (1.018 vs. 0.511, p = 0.023) and 8 weeks (1.006 vs. 0.596, p = 0.018). In addition, CREB phosphorylation was inhibited in GDM group, with fewer activated pCREB proteins binding to the CRE element of Ppargc1α (1.042 vs. 0.681, p = 0.037), Pck1 (1.091 vs. 0.432, p = 0.014) and G6pc (1.118 vs. 0.472, p = 0.027), resulting in their d","PeriodicalId":19339,"journal":{"name":"Nutrition & Diabetes","volume":"14 1","pages":"56"},"PeriodicalIF":4.6,"publicationDate":"2024-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11266655/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752275","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}