Diabetes最新文献

{"title":"Disrupting the PNPLA3-ABHD5 Interaction Stimulates Lipolysis and Improves PNPLA3-I148M-Associated Hepatic Steatosis.","authors":"Simon Steinbring Hoffman, Emily Tso Newman, Daniel Lin, Michelle Chen, Song Yang, Alan Cheng, Thomas W Rosahl, Heather H Zhou, Saswata Talukdar, Yingjiang Zhou","doi":"10.2337/db26-0108","DOIUrl":"https://doi.org/10.2337/db26-0108","url":null,"abstract":"<p><strong>Article highlights: </strong>We evaluate the importance of the protein-protein interaction (PPI) between PNPLA3-I148M and its cofactor α/β-hydrolase domain-containing protein 5 (ABHD5) in PNPLA3-I148M-mediated hepatic steatosis. We demonstrate that disrupting the PNPLA3-ABHD5 PPI improves I148M-associated steatosis and markers of liver injury. This work supports the development of therapies targeting the PNPLA3-ABHD5 PPI for the treatment of PNPLA3-I148M-associated metabolic dysfunction-associated steatotic liver disease.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Accelerated Epigenetic Ageing in Diabetic Kidney Disease: A Comparison of 10 Epigenetic Clock Measures in Individuals With Type 1 Diabetes.","authors":"Claire Hill, Xiaoqi Luo, Anna Syreeni, Laura Smyth, Emma H Dahlström, Seamus Duffy, Jill Kilner, Abubakar Mangani, Alicia J Jenkins, Gareth McKay, Alexander P Maxwell, Eoin P Brennan, Catherine Godson, Joel N Hirschhorn, Jose C Florez, Per-Henrik Groop, Niina Sandholm, Amy Jayne McKnight","doi":"10.2337/db26-0089","DOIUrl":"https://doi.org/10.2337/db26-0089","url":null,"abstract":"<p><strong>Article highlights: </strong>We investigated whether an association existed between epigenetic age acceleration (EAA) and diabetic kidney disease (DKD) in type 1 diabetes, using 10 clocks and two cohorts, and whether this amplified disease progression. Older EAA phenotypic age and shorter epigenetically predicted telomere lengths were significantly associated with DKD. Progression from normolbuminuria to severely increased albuminuria was associated with increased EAA, and age, epigenetic age, and EAA were significant predictors of progression to end-stage kidney disease. Results support the development of epigenetic biomarkers predicting DKD onset and progression.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Trial Design Considerations for the Development of Disease-Modifying Therapies for Type 1 Diabetes.","authors":"Joshua A Vieth, Randy L Anderson, Sumitra Ghate, Linda A DiMeglio, Francisco Leon, Sanjoy Dutta, Esther Latres, Stephen R Karpen","doi":"10.2337/db26-0097","DOIUrl":"https://doi.org/10.2337/db26-0097","url":null,"abstract":"<p><strong>Article highlights: </strong>Several disease-modifying therapies have reduced the progressive loss of β-cell function in type 1 diabetes, with efficacy observed across a wide array of underlying therapeutic mechanisms of action. These successes highlight opportunities to accelerate the development of novel and repurposed type 1 diabetes treatments; however, only one such therapy has received regulatory approval for clinical use and few phase 3 clinical trials have been performed. For bringing emerging therapies to people living with type 1 diabetes as quickly and efficiently as possible, overall regulatory strategy and clinical trial design, especially inclusion criteria and end point selection, are essential, and planning must include their careful consideration. The considerations discussed herein represent a feasible and promising road map for developers of disease-modifying therapies and establish that type 1 diabetes remains a promising area for continued investment.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149229528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Classification Algorithm for Diabetes Subtypes in a Swedish Cohort: Comparison With National Diabetes Register Diagnoses and Genetic Validation.","authors":"Shobitha Vollmer, Alice Maguolo, Axel Lindström, Lucas Maurin, Manonanthini Thangam, Sonia García-Calzón, Emma Ahlqvist, Katarina Fagher, Charlotte Ling","doi":"10.2337/db26-0524","DOIUrl":"https://doi.org/10.2337/db26-0524","url":null,"abstract":"<p><strong>Article highlights: </strong>Diabetes subtype-specific research is challenging when using data from large registers, and validation studies of Swedish National Diabetes Register (NDR) diagnoses remain limited. We aimed to develop an algorithm to classify diabetes subtypes using linked longitudinal data, compare with NDR, and validate it using polygenic risk scores. We developed an algorithm that reliably distinguishes diabetes subtypes with higher granularity compared with NDR and is validated by polygenic risk scores. Our algorithm reveals clinically meaningful heterogeneity that may be overlooked in registers and enables subtype-specific diabetes research.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149140043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hyperglycemia Drives an Activated, Lipid-Laden Nonclassical Monocyte Phenotype in Diabetes.","authors":"Jocelyn Cervantes, Anika Consul, Alan Tran, Jingjing Tang, Farah Kramer, Huaqing Zheng, Adam E Mullick, Tomas Vaisar, Francis Kim, Karin E Bornfeldt, Baohai Shao, Jenny E Kanter","doi":"10.2337/db26-0085","DOIUrl":"https://doi.org/10.2337/db26-0085","url":null,"abstract":"<p><strong>Article highlights: </strong>Although monocytes can accumulate lipids, whether diabetes alters monocyte lipid loading is unknown. Nonclassical monocytes accumulate more lipids via a process that is partly regulated by hyperglycemia in people with diabetes and in three different mouse models of diabetes. Increased lipid loading promotes a more activated monocyte phenotype. Nonclassical monocytes contribute to the accumulation of foamy kidney macrophages in a mouse model of diabetic kidney disease.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Olive Oil Before Oral Glucose Delays Gastric Emptying and Lowers Glycemia Through Partially Redundant Glucagon and GLP-1 Signaling in Mice.","authors":"Yanyan Liu, Hiromi Tsuchida, Sodai Kubota, Saki Kubota-Okamoto, Takehiro Kato, Yukio Horikawa, Shin Tsunekawa, Hitoshi Kuwata, Yuuka Fujiwara, Yuji Yamazaki, Yuichiro Yamada, Hiroki Fujita, Katsumi Iizuka, Naoya Murao, Shinji Ueno, Yusuke Seino, Atsushi Suzuki, Yoshitaka Hayashi, Tsuyoshi Nakanishi, Daniel J Drucker, Takahiko Shiina, Yasutake Shimizu, Yusaku Iwasaki, Toshihiko Yada, Yohei Seno, Yuya Takahashi, Toshinori Imaizumi, Takaaki Murakami, Michael Horowitz, Yutaka Seino, Daisuke Yabe","doi":"10.2337/db26-0531","DOIUrl":"https://doi.org/10.2337/db26-0531","url":null,"abstract":"<p><strong>Article highlights: </strong>We undertook this study to define how fat consumed before oral glucose attenuates postchallenge glycemia. We asked whether olive oil reduces glycemia by slowing gastric emptying and investigated contributing endocrine and neural pathways. Olive oil increased glucagon, glucose-dependent insulinotropic polypeptide, and glucagon-like peptide-1; slowed gastric emptying; and reduced early glycemia in mice. Glucagon and glucagon-like peptide-1 signaling acted redundantly, with vagal involvement. Nutrient timing integrates endocrine-neural regulation of gastric emptying and glycemia, supporting evaluation of meal sequencing in humans.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149139957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Microgels Containing Protease Resistant CXCL12 and FasL Enable Long-term Allo-Islet Function Without Systemic Immunosuppression.","authors":"Fatma Dogan, Assia El Babsiri, Esin Ozkan, Sitong Ye, Katie Lu, Aaruni Arora, Kento Kawai, Ryo Otsuka, Timothy A Brauns, Patrick M Reeves, Ann E Sluder, Mark C Poznansky","doi":"10.2337/db26-0280","DOIUrl":"https://doi.org/10.2337/db26-0280","url":null,"abstract":"<p><strong>Article highlights: </strong>Cotransplantation of allogeneic islets with microgels coated with streptavidin fused with Fas ligand and protease-resistant CXCL12 results in robust and sustained diabetes reversal for over 6 months in streptozotocin-induced diabetic mice and induces local immunomodulation, enhances Treg recruitment within the graft, and improves graft vascularization. This study addresses a critical challenge in cell transplantation, namely the need to develop technologies that enable local immunoprotection of the graft while eliminating the need for systemic immunosuppression. This combination microgel technology could offer a more favorable risk-benefit profile by reducing infection risks, organ toxicity, and tumorgenicity associated with the use of systemic immunosuppression. This novel combinatory immune modulatory approach is feasible and achieves anatomic site-specific immune protection while supporting long-term islet graft function without systemic immune suppression.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149077192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nod1 Plays a Causal Role in Palmitate-Induced β-Cell Dysfunction In Vitro and In Vivo in Male Mice.","authors":"Justin H M Yung, Emily G Hoffman, Aleksandar Ivovic, S M Niazur Rahman, Tejas Desai, Khajag Koulajian, Yusaku Mori, Charles Maisonneuve, Marry Nissan, Ayse Bengisu Gelmez, Yasmin Rabiee, Sandra Pereira, Dana Al-Rijjal, Michael B Wheeler, Dana J Philpott, Adria Giacca, Kacey J Prentice","doi":"10.2337/db25-0752","DOIUrl":"https://doi.org/10.2337/db25-0752","url":null,"abstract":"<p><strong>Article highlights: </strong>The innate immunity receptor nucleotide-binding oligomerization domain 1 (Nod1) can be activated by saturated fatty acids and is implicated in high-fat diet-induced inflammation and insulin resistance. This implies Nod1 plays a role in glucose homeostasis; therefore, we sought to determine whether saturated fatty acids cause pancreatic β-cell dysfunction through Nod1. Our data demonstrate that Nod1 is involved in palmitate-induced β-cell dysfunction in vitro and in vivo.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018959","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reduction in T-Cell Mitochondrial Respiratory Capacity After Reaching a Weight Loss Plateau.","authors":"Ana P Valencia, Arthur F Brandao, Susan J Melhorn, Mary Rosalynn B De Leon, David J Marcinek, Ellen A Schur","doi":"10.2337/db26-0304","DOIUrl":"https://doi.org/10.2337/db26-0304","url":null,"abstract":"<p><p>Experiencing an involuntary weight loss plateau is common after behavioral weight loss. During such periods, sustained negative energy balance activates counterregulatory mechanisms that restore energy balance and may slow further weight loss. However, the cellular bioenergetic changes occurring specifically during a spontaneous weight loss plateau have not been investigated. We studied mitochondrial respiratory capacity in peripheral mononuclear cell populations from participants with obesity, both before and after an intensive lifestyle intervention (ILI). Body weight was tracked continuously over 18 months using a remote electronic scale, enabling retrospective categorization of outcome measures by weight loss phases: active weight loss (aWL), plateau (PL), or regain (RG). Differences in mitochondrial respiration were observed in T cells but not in monocytes across these phases. During aWL, mitochondrial respiratory capacity was similar to pre-ILI; however, basal, ATP-linked, maximal, and spare respiratory capacity were significantly lower during the PL and RG phases. In addition, ATP-linked respiration was lower in the PL and RG, despite higher mitochondrial citrate synthase activity in the PL relative to pre-ILI. These results indicate that T-cell bioenergetics may be responsive to shifts in energy balance during weight reduction. The novel phase-specific classification used in this study uncovers dynamic bioenergetic adaptations that may contribute to a weight loss plateau.</p><p><strong>Article highlights: </strong>Weight loss is a dynamic process, characterized by transitions between active weight loss, plateau, and regain, yet underlying metabolic features across these phases remain poorly defined. This study tested whether mitochondrial bioenergetics in peripheral mononuclear cells differ in humans across weight loss phases during behavioral weight loss. Mitochondrial respiratory capacity of T cells is significantly reduced during plateau and regain phases, despite an increase in mitochondrial content. Phase-based classification of weight change reveals bioenergetic differences in T cells that are associated with transitions in energy balance within the weight-reduced state.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Norrin Treatment Prevents Vascular Permeability and Neural Cell Loss While Preserving Vision in Diabetic Rats.","authors":"Laura González-González, Alyssa Dreffs, Cheng-Mao Lin, Xuwen Liu, Ethan Hendry, David A Antonetti","doi":"10.2337/db26-0340","DOIUrl":"https://doi.org/10.2337/db26-0340","url":null,"abstract":"<p><strong>Article highlights: </strong>We investigated whether norrin treatment can prevent or reverse diabetes-induced visual dysfunction in rats. Norrin treatment preserved visual acuity and contrast sensitivity, reduced neural cell death, inflammation, and vascular permeability, and restored inflammation-related gene expression patterns in diabetic retinas. Our results support targeting the norrin signaling pathway as a potential therapy for maintaining blood-brain barrier properties and preventing vision loss due to diabetes.</p>","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979169","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}