Diabetes最新文献

{"title":"Amino Acid Profiles Distinguish Glycemic Phenotypes in Childhood and Predict 10-Year Risk of Dysglycemia in Young Adults: The BCAMS Study","authors":"Mengyu He, Yu Li, Xinghao Yi, Danyang Li, Siyu Wu, Haoxue Zhu, Jing Guo, Jinjin Tian, Ming Li, Shan Gao","doi":"10.2337/db26-0337","DOIUrl":"https://doi.org/10.2337/db26-0337","url":null,"abstract":"Amino acid (AA) dysregulation has been associated with metabolic diseases. However, its potential as a childhood determinant of adult diabetes risk remains understudied, particularly among children with normoglycemia. Leveraging a 10-year follow-up cohort, we investigated whether AA profiles distinguished childhood glycemic phenotypes and predicted future diabetes risk. Among 947 children from the Beijing Children and Adolescents Metabolic Syndrome (BCAMS) study, participants were categorized as having normoglycemia with insulin sensitivity (NG-IS), normoglycemia with insulin resistance (NG-IR), or impaired fasting glucose (IFG), and plasma AA profiles were assessed by targeted metabolomics. At follow-up, 297 participants with baseline normoglycemia underwent a 2-h oral glucose tolerance test to assess incident dysglycemia, and five adipokines were measured. After adjusting for age, sex, and relevant covariates, distinct AA signatures were identified cross-sectionally across glycemic groups, with a core cluster (Ile, Val, Tyr, Phe, Ala, Pro, and branched-chain AA score) independently associated with IR and IFG. Prospectively, children in the NG-IR group had a 4.3-fold higher risk of incident dysglycemia than those in the NG-IS group. Six AAs (Ile, Leu, Tyr, Phe, Lys, and Hyl) significantly predicted 10-year dysglycemia risk, with 22.6–42.1% of their associations estimated through follow-up IR, with the largest proportion observed for Ile. In separate Ile–IR models, estimated proportions through follow-up leptin and high-molecular-weight adiponectin were 72% and 38%, respectively. Furthermore, dietary Ile restriction in obese mice reduced body weight by 25% and leptin by 50% and improved IS by 22%. These findings identify childhood plasma AA dysregulation as an early biomarker for diabetes risk, and Ile emerges as a potentially modifiable target. Article Highlights Prospective evidence linking childhood amino acid (AA) dysregulation with future diabetes risk remains limited. We examined whether AA profiles distinguished childhood glycemic phenotypes and predicted dysglycemia risk in the Beijing Children and Adolescents Metabolic Syndrome (BCAMS) cohort. AA alterations were already detectable in children with normoglycemia and insulin resistance; six AAs were associated with 10-year dysglycemia risk, and their addition to clinical variables improved prediction. Ile showed the largest estimated indirect association with incident dysglycemia through follow-up insulin resistance; dietary Ile restriction in obese mice produced concordant metabolic changes, supporting AA profiling for early risk identification and Ile as a candidate modifiable target.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"55 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149218574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum. 1991-LB: Triglyceride–Glucose Index Is an Effective Tool for Assessing Glycemic Control in Asian Indians with Type 2 Diabetes. Diabetes 2024;73(Suppl. 1):1991-LB","authors":"Rajendra Pradeepa, Vinitaa Jha, Pramodkumar Thyparambil Aravindakshan, Swati Waghdhare, Viswanathan Mohan, John Chambers, Ranjit Mohan Anjana","doi":"10.2337/db27-er01e","DOIUrl":"https://doi.org/10.2337/db27-er01e","url":null,"abstract":"In the above-cited abstract, the funding information was incomplete as published; the complete funding information is given below. “This research was funded by the National Institute for Health and Care Research (NIHR) (NIHR132960) using U.K. international development funding from the U.K. Government to support global health research. The views expressed in this publication are those of the author(s) and not necessarily those of the NIHR or the U.K. Government.” The authors apologize for the error. The abstract (https://doi.org/10.2337/db24-1991-LB) has been updated with the correct text.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"48 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198941","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum. 1800-P: GLP-1 Use in Type 1 Diabetes Patients: Assessing Changes in HbA1c, Body Weight, and Cardiovascular Disease Risk Reduction. Diabetes 2026;75(Suppl. 1):1800-P","authors":"Mushgan Nassiri, Maryam Amir","doi":"10.2337/db27-er02e","DOIUrl":"https://doi.org/10.2337/db27-er02e","url":null,"abstract":"In the above-cited abstract, author Maryam Amir did not appear in the original author list due to a technical error. The abstract (https://doi.org/10.2337/db26-1800-P) has been updated with the original, correct author list.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"11 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149198940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Incretin-Dependent Modulation of Periprandial Neutrophilia","authors":"Andrea Baragetti, Lorenzo Da Dalt, Anna Parolini, Annalisa Moregola, Elisa Nespoli, Ottavia Terenghi, Alessandra M. Martorana, Monika Svecla, Tito Borner, Thomas A. Lutz, Tomasz J. Guzik, Mateusz Siedlinski, Giuseppe Danilo Norata","doi":"10.2337/db25-1064","DOIUrl":"https://doi.org/10.2337/db25-1064","url":null,"abstract":"Daily cycles of fasting and feeding shape systemic metabolism, yet how innate immunity senses these transitions remains unclear. Chronic high-fat diet (HFD) primes granulocyte-monocyte progenitors to generate clones with heightened inflammasome activity and excessive production of interleukin-6 (IL-6) and IL-1β. Whether periprandial states influence immune surveillance remains unknown. We profiled periprandial immune adaptations in mice fed an HFD (60% energy from fat) or standard-fat diet (SFD) after overnight fasting and up to 4 h postfeeding, integrating blood immunophenotyping, endotoxin challenges, and neutrophil activation markers. Neutrophil counts rose within 15 min of feeding, preceding monocytosis (≥2–4 h). Neutrophilia during SFD, but not HFD, refeeding was associated with lower lipopolysaccharide-induced sickness, suggesting that it is critical for the host to microbial challenges. This early neutrophilia was enhanced by HFD and further amplified with the establishment of insulin resistance following 7 days of HFD feeding. We link this response to intestinal fat absorption and to the coordinated glucagon-like peptide 1 (GLP-1)/insulin regulation of the periprandial responses. Yet, GLP-1 receptor (GLP-1R) antagonism potentiated neutrophilia during HFD feeding, whereas coadministration of insulin abolished it. After 7 days of HFD adaptation, this insulin effect was lost, linking GLP-1 action to insulin sensitivity. In humans, periprandial neutrophilia was also observed, and it was altered in type 2 diabetes, independent from C-reactive protein, IL-6, and IL-1β. Feeding elicits a rapid neutrophil response established to provide immune resilience during nutrient absorption. These findings uncover a GLP-1–insulin-dependent axis coordinating immunometabolic adaptation to the periprandial state. Article Highlights We determine how innate immunity adapts to transitions between fasting and feeding. Feeding rapidly induced periprandial neutrophilia. HFD accelerated this reponse. We therefore sought to examine whether periprandial states regulate neutrophil dynamics. We identified that the glucagon-like peptide 1 and insulin axis modulates the neutrophil surge, which is critical during endotoxin challenges. The periprandial state prepares the host for endotoxemia. We bridge nutrient intake and incretin-sensitive immunity to inflammatory tone, redefining postprandial inflammation, insulin resistance, and cardiometabolic risk in diabetes.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"33 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187869","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reversal of T1D and Rapid Reduction of β-Cell Stress by IL-10–Dependent MDSCs Induced by TLR4-Ab","authors":"Nicolle K. Martin, Luke S. Heuer, Ixchel M. Urbano, Shana L. Cohen, Manuel Rojas, Weici Zhang, Kyle J. Bednar, Bethany P. Cummings, William M. Ridgway","doi":"10.2337/db26-0636","DOIUrl":"https://doi.org/10.2337/db26-0636","url":null,"abstract":"Type 1 diabetes (T1D) is caused by the autoimmune destruction of insulin-producing pancreatic β-cells. We published that an IgG3 Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) agonistic antibody (TLR4-Ab) reversed acute T1D in NOD mice by induction of myeloid-derived suppressor cells (MDSCs), but the mechanism of MDSC induction was unclear. Here we show that TLR4-Ab reversal of acute T1D induced profound intraislet immune and endocrine changes in single-cell RNA sequencing compared with controls. Islet-infiltrating S100A9+ cells significantly upregulated 18 genes associated with MDSCs, including Nos2, the gene responsible for inducible nitric oxide synthase (iNOS) production. TLR4-Ab treatment induced significant changes in β-cell gene expression, with markedly reduced endoplasmic reticulum stress and reduced unfolded protein response. Bone marrow (BM) cells cultured with TLR4-Ab, but not granulocyte macrophage–colony-stimulating factor or lipopolysaccharide, induced MDSCs that suppressed T cells, and blockade of iNOS activity eliminated T-cell suppression. Blockade of interleukin 10 (IL-10) signaling during BM differentiation prevented T-cell suppression induced by TLR4-Ab–MDSC, demonstrating a central role for IL-10 in TLR4-Ab–mediated MDSC development. Reporter cell assays demonstrated predominant endosomal signaling with TLR4-Ab, and soluble (not plate-bound) TLR4-Ab was necessary for MDSC induction. TLR4-Ab treatment of T1D therefore induces an IL-10–dependent immunoregulatory MDSC response, which significantly downregulates β-cell stress. Article Highlights Therapy with IgG3 Toll-like receptor 4 (TLR4)/myeloid differentiation factor 2 (MD2) agonistic antibody (TLR4-Ab) is a novel approach to type 1 diabetes (T1D) immunotherapy that targets the innate immune system by inducing immunoregulatory myeloid-derived suppressor cells (MDSCs). We sought to define the mechanisms by which TLR4-Ab induces MDSCs and how they reverse T1D. TLR4-Ab induction of MDSCs requires interleukin 10 signaling in the bone marrow, and MDSCs mediate suppression via inducible nitric oxide synthase. Induction of immunoregulatory MDSCs results in profound downregulation of β-cell endoplasmic reticulum stress and unfolded protein response associated with acute T1D. Establishing mechanisms by which TLR4-Ab reverses acute T1D defines new therapeutic pathways for human T1D that target innate immunity to restore immune tolerance.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"10 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187884","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal Muscle DPT Ameliorates Obesity and Metabolic Dysfunction via the PERK/eIF2α/ATF4-GDF15 Axis","authors":"Lingxin You, Bo Xu, Tingting Wen, Ying Chen, Lijun Yao, Zhuo Chen, Baocheng Wan, Fan Yang, Xiangtian Yu, Rong Zhang, Hong Zhang, Jing Yan, Cheng Hu","doi":"10.2337/db26-0082","DOIUrl":"https://doi.org/10.2337/db26-0082","url":null,"abstract":"Skeletal muscle plays a pivotal role in maintaining metabolic homeostasis by acting as a primary site for glucose disposal and insulin-mediated energy use. Here, through RNA sequencing of skeletal muscle from individuals with normal weight versus obesity, we identified that the extracellular matrix–related gene dermatopontin (DPT) was significantly upregulated in the individuals with obesity. By establishing muscle-specific overexpression, knockdown, and knockout Dpt mouse models, we demonstrated that DPT ameliorated metabolic dysfunction by improving muscular mitochondrial function and exercise capacity, systemic insulin sensitivity, and glucose tolerance while reducing hepatic steatosis, suppressing appetite, and synergistically boosting energy expenditure under high-fat-diet feeding. Mechanistically, DPT activated a compensatory increase in the PERK/eIF2α/ATF4 endoplasmic reticulum stress pathway, leading to the transcriptional upregulation of growth differentiation factor (GDF) 15 expression and secretion. Importantly, the metabolic benefits of DPT were abolished in Gdf15−/− mice. Collectively, our study identified DPT as a novel, compensatorily expressed regulator in muscle during obesity, highlighting its potential as a therapeutic target for treating metabolic disorders. Article Highlights We identified dermatopontin (DPT) as a previously unrecognized compensatory regulator that is upregulated in skeletal muscle in obesity and preserves muscle function and systemic metabolic homeostasis, offering a potential therapeutic target for metabolic disorders. Mechanistically, DPT activates an adaptive PERK/eIF2α/ATF4 endoplasmic reticulum stress axis specifically under metabolic stress, but not under normal conditions, which enhances muscle function and directly counteracts metabolic deterioration, revealing a protective signaling cascade. This DPT-driven endoplasmic reticulum stress axis transcriptionally upregulates growth differentiation factor (GDF) 15 expression and secretion in muscle. Muscle-derived GDF15 exerts both local muscle-autonomous and systemic protective effects, uncovering a previously unrecognized muscle-to-organ cross-talk axis.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"18 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Dysfunction Across Renal Compartments in Diabetic Kidney Disease","authors":"Abigail Shapiro, Ratnakar Tiwari, Alexander Staruschenko","doi":"10.2337/dbi26-0024","DOIUrl":"https://doi.org/10.2337/dbi26-0024","url":null,"abstract":"Diabetic kidney disease (DKD) remains a leading cause of chronic kidney disease and kidney failure despite considerable therapeutic progress. Mitochondrial dysfunction has emerged as a central mechanism linking diabetic metabolic stress to progressive renal injury, yet it is often described as a generalized, whole-kidney abnormality. This view is incomplete because renal compartments differ in metabolic demand, substrate preference, oxygen exposure, mitochondrial density, and repair capacity. Therefore, diabetes is unlikely to induce a uniform mitochondrial defect across the kidney. Here, we introduce a compartment- and stage-specific framework that integrates evidence from proximal tubules, distal nephron segments, glomerular endothelial cells, podocytes, mesangial cells, immune cells, and interstitial compartments. Using this framework, we define how mitochondrial metabolism, dynamics, quality control, redox signaling, mtDNA stress, and inflammatory pathways contribute to DKD progression across distinct renal cell types. We highlight which mitochondrial programs are most clearly implicated in specific renal compartments, where evidence remains limited, and how understudied cell types may contribute to disease progression. This cell- and stage-specific framework provides a basis for interpreting mitochondrial dysfunction by renal compartment and biological context rather than as a single kidney-wide process. Moving beyond bulk mitochondrial measurements toward spatial, functional, and cell-specific mitochondrial phenotyping may clarify whether mitochondrial responses are adaptive, injurious, or reversible and support therapeutic strategies directed toward the relevant mitochondrial programs in the appropriate compartment and at the appropriate disease stage. Article Highlights Mitochondrial dysfunction in diabetic kidney disease is compartment and stage specific, reflecting differences in renal cell metabolism, function, and injury response. This article introduces a framework for interpreting mitochondrial dysfunction across renal cell types and disease stages. Proximal tubular stress progresses from increased transport demand to mitochondrial injury and impaired quality control. Distal nephron, immune, and interstitial mitochondrial mechanisms remain incompletely defined. In glomerular endothelial cells and podocytes, mitochondria primarily regulate stress and injury signaling. Cell-specific mitochondrial phenotyping may reveal reversible pathways and guide more precise therapeutic strategies in diabetic kidney disease.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"477 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149151810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The American Diabetes Association at a Crossroads","authors":"David A. D’Alessio","doi":"10.2337/dbi26-0051","DOIUrl":"https://doi.org/10.2337/dbi26-0051","url":null,"abstract":"","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"17 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Members of the American Diabetes Association Board of Directors","authors":"David D’Alessio,Jonathan Campbell,Lisa Chow,Steven Crowley,Dawn Belt Davis,Jennifer Estall,Carmella Evans-Molina,Rana Gupta,Kirk Habbeger,Rebecca Haeusler,Mark Herman,David Hodson,Soo-Heon Kwak,Daniela Maria Menichella,Erin Mulvihill,Christopher Newgard,Darleen Sandoval,Norbert Stefan,Jennifer Sun,John Ussher,Bruce Verchere,Kevin Williams,Daisuke Yabe,Sylvaine You","doi":"10.2337/dbi26-0052","DOIUrl":"https://doi.org/10.2337/dbi26-0052","url":null,"abstract":"","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"5 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089113","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the American Diabetes Association Board of Directors From Members of the Mentor Advisory Committee, ADA Pathway to Stop Diabetes Program","authors":"Barbara Anderson,Mark Anderson,David D’Alessio,Mary de Groot,Robert Eckel,David Harlan,Kevan Herold,Elbert Huang,Rohit Kulkarni,Lori Laffel,Christopher Newgard,Kathleen Page,Stephen Parker,Sumita Pennathur,Louis Phillipson,Lauretta Quinn,Alan Saltiel,Jean Schaffer,Viral Shah,Andrew Stewart,Karen Talmadge,Jill Weissberg-Benchell,Phillip White","doi":"10.2337/dbi26-0053","DOIUrl":"https://doi.org/10.2337/dbi26-0053","url":null,"abstract":"","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"76 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149089114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}