Diabetes最新文献

{"title":"A Selective Cullin 3 RING E3 Ligase Inhibitor Attenuates Hyperglycemia via Dual Insulin Sensitizing and Insulinotropic Action","authors":"Lijie Gu, Lei Xiong, Mohammad Nazmul Hasan, Yanhong Du, Timothy Wu, Tiangang Li","doi":"10.2337/db26-0029","DOIUrl":"https://doi.org/10.2337/db26-0029","url":null,"abstract":"Hyperglycemia is a hallmark of type 2 diabetes and a key pathogenic driver of diabetes complications. Cullin RING E3 ligases (CRLs) are multisubunit E3 ubiquitin ligases that mediate cellular protein turnover. The activity of CRLs requires cullin neddylation, a posttranslational modification that can be pharmacologically targeted with therapeutic potentials. By using hyperinsulinemic euglycemic clamp analysis, we discover that pan-neddylation inhibitor exerts both an insulin sensitization effect in liver and muscle and an insulinotropic effect in pancreatic β-cells. This dual action is mediated by cullin 3 (Cul3), a member of the seven canonical cullin family proteins. DI-1859, a selective Cul3 neddylation inhibitor, effectively protects against hyperglycemia in obese mice. DI-1859 enhances insulin signaling by preventing Cul3-mediated insulin receptor substrate degradation in liver and muscle cells. DI-1859 increases insulin secretion in a glucagon-like peptide-1–independent manner in mice and directly enhances insulin secretion in INS-1 832/13 β-cells and human islets. Cul3 inhibition leads to Ras homolog family member A (RhoA) stabilization. RhoA regulation of cytoskeleton remodeling may play a role in mediating the insulinotropic effect of DI-1859 in β-cells. In conclusion, this study demonstrates that a single agent targeting Cul3 neddylation promotes peripheral insulin sensitization and β-cell insulin secretion to attenuate hyperglycemia in mice. Article Highlights Pan-neddylation inhibitors exhibit potent hypoglycemic effect. The target organs and mechanisms underlying the hypoglycemia effect of pan-neddylation inhibitors are incompletely understood. We found that inhibition of cullin 3 leads to a dual insulin sensitization and insulinotropic effect. Selective inhibition of cullin 3 neddylation is a feasible approach to lower hyperglycemia.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"68 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633862","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":"Myeloid-Specific Heparanase Aggravates Insulitis in Type 1 Diabetes via Heparan Sulfate Fragment-Dependent Amplification of Macrophage Polarization","authors":"Jia Zhang, Meiwei Li, Xiaohang Zhou, Hailing Ni, Yiyue Huang, Xin Hu, Huangmo Lin, Xinyuan Cao, Xiao Han, Peng Sun","doi":"10.2337/db26-0365","DOIUrl":"https://doi.org/10.2337/db26-0365","url":null,"abstract":"The intraislet heparan sulfate (HS) barrier is essential for β-cell survival, yet its role in type 1 diabetes (T1D) remains incompletely understood. We investigated the expression pattern, pathogenic function, and therapeutic potential of the heparanase (HPSE)-HS axis in T1D by integrating single-cell RNA sequencing data sets from human and mouse islets and peripheral immune cells, together with genetic mouse models and pharmacological intervention. HPSE was selectively enriched in myeloid cells, particularly CD14++ classical monocytes from patients with T1D and NOD mice and was associated with activated proinflammatory and interferon signaling. In diabetic islets, increased HPSE expression was accompanied by marked degradation of the HS barrier. Myeloid-specific Hpse deficiency improved glucose tolerance, enhanced insulin secretion, and reduced infiltration of inducible nitric oxide synthase–positive macrophages and T cells, whereas islet-specific Hpse overexpression accelerated autoimmune diabetes and insulitis. Mechanistically, HPSE-mediated HS cleavage generated bioactive fragments that acted as costimulatory signals, amplifying IFN-γ–STAT1 signaling and promoting M1 macrophage polarization. Pharmacological inhibition of HPSE with muparfostat preserved the intraislet HS barrier and improved glucose homeostasis in nonobese T1D models. Collectively, these findings identify myeloid-derived HPSE as a key driver of T1D pathogenesis through dual effects on HS barrier disruption and inflammatory amplification and establish the HPSE-HS axis as an important regulator of the islet inflammatory microenvironment and a promising adjuvant therapeutic target for T1D. Article Highlights The role of the heparanase (HPSE)–heparan sulfate (HS) axis in type 1 diabetes remains incompletely defined. We examined whether myeloid-derived HPSE drives islet inflammation, how HS fragments influence macrophage polarization, and whether pharmacological inhibition is protective. We found that myeloid HPSE disrupts the intraislet HS barrier and that the resulting HS fragments potentiate interferon-γ–STAT1 signaling to promote proinflammatory macrophage polarization. Genetic or pharmacological inhibition of HPSE preserved islet integrity and ameliorated diabetes, identifying this pathway as a potential therapeutic target in type 1 diabetes.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"47 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633863","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":"Dual Modulation of Prostaglandin E2 Receptors EP3 and EP4 Protects β-Cell Mass in a Model of Aggressive Autoimmune Inflammation","authors":"Juliann B. Burkett, Jennifer Fuhr, Alexander C. Falk, Prasanna Dadi, Alexa N. Del Bene, Audrey Lucerne, Dudley McNitt, Landon M. Clark, Micaela Maxwell, Victoria Gaeth, Kaelyn Allen, David Jacobson, Daniel J. Moore, Christopher S. Wilson, Maureen Gannon","doi":"10.2337/db25-1007","DOIUrl":"https://doi.org/10.2337/db25-1007","url":null,"abstract":"Type 1 diabetes is driven by both β-cell dysfunction and an autoreactive immune system, resulting in β-cell destruction and hyperglycemia. We previously showed that pharmacological modulation of prostaglandin E2 (PGE2) receptor (EP) signaling protects β-cells from cytokine-mediated death ex vivo, and relieves oxidative stress and maintains β-cell identity in a mouse model of type 2 diabetes. Here we show that EP modulation protects against cytokine-mediated β-cell death in islets from nonobese diabetic (NOD) mice. Because PGE2 can also alter immune cell phenotypes, we tested whether EP modulation prevents β-cell destruction in a setting of aggressive autoimmunity in vivo. Simultaneous blockade of the inhibitory EP3 receptor and activation of the stimulatory EP4 receptor delayed onset of hyperglycemia, prevented loss of β-cell mass, and reduced insulitis in cyclophosphamide-treated female NOD mice. Despite reduced insulitis, there were no changes in several systemic T-cell populations, including regulatory T cells. However, EP modulation altered islet cytokine expression and, within β-cells, preserved identity, sustained activation of the antioxidant factor NRF2, and reduced evidence of senescence. Thus, the PGE2 signaling pathway is a potential target for protecting β-cell mass under aggressive autoimmune attack to treat or prevent type 1 diabetes. Article Highlights Modulation of prostaglandin E2 (PGE2) signaling improves β-cell health and survival. In this study, we examined whether these β-cell effects could be harnessed alongside known PGE2-mediated immunomodulation to ameliorate β-cell loss in a model of severe islet autoimmunity. Simultaneous pharmacological blockade of the EP3 receptor and activation of the EP4 receptor maintain mature β-cell mass, ameliorate the proinflammatory insulitic microenvironment, and alter β-cell stress responses in female nonobese diabetic mice undergoing aggressive inflammatory assault. EP modulation shows promise to support β-cell resiliency and reduce inflammation in a setting of autoimmune attack, such as type 1 diabetes.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"85 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148633763","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":"Integrated Fat-Muscle Patterns Drive Sex-Specific Diabetes Risk: UK Biobank Evidence","authors":"Yifan Ma, Ning Zhou, Boya Yu, Zixiao Liang, Mengjie Xiao, Guoqiang Jing, Xu Zhang, Xin Liu, Changhao Sun, Huanyu Wu","doi":"10.2337/db26-0096","DOIUrl":"https://doi.org/10.2337/db26-0096","url":null,"abstract":"This study aimed to identify integrated body composition patterns and evaluate their sex-specific associations with incident type 2 diabetes (T2D). Among 258,500 UK Biobank participants free of diabetes at baseline, principal component analysis (PCA) was applied to 28 anthropometric, fat, lean, bone, and muscle strength traits. Cox models assessed associations with incident T2D, and least absolute shrinkage and selection operator (LASSO)-penalized Cox and weighted quantile sum (WQS) regression identified key components. During a mean follow-up of 11 years, 33,636 incident T2D cases were identified. PCA yielded seven interpretable patterns. LASSO consistently identified generalized adiposity, leg-dominant lean distribution, and central leanness as robust components across sexes. Compared with the low-score reference group, generalized adiposity was associated with higher T2D risk in men and women (hazard ratio [HR] 1.73 [95% CI 1.33–2.24] and 2.21 [1.55–3.16], respectively), whereas leg-dominant lean distribution was associated with lower risk (HR 0.57 [0.48–0.68] and 0.50 [0.40–0.63]). Central leanness was associated with lower risk in women (HR 0.41 [0.34–0.51]) and showed a nonmonotonic association with risk in men. In WQS analyses, central leanness contributed more strongly to the inverse mixture association in men, whereas leg-dominant lean distribution contributed more strongly in women. These findings highlight sex-specific fat-lean configurations in diabetes risk. Article Highlights Conventional obesity measures do not capture the multidimensional nature of body composition or the integrated distribution of fat and lean tissue. We aimed to identify integrated body composition patterns and determine their sex-specific associations with incident type 2 diabetes risk. We identified distinct composite body composition patterns associated with diabetes risk in men and women, with generalized adiposity linked to higher risk and leg-dominant lean distribution or central leanness linked to lower risk. These findings suggest that multidimensional fat-muscle patterns provide complementary information beyond conventional obesity measures for understanding diabetes risk.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"101-B 10 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148461859","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":"High-Frequency Feeding With Late-Night Snacking Accelerates Type 2 Diabetes and Alters Diurnal Metabolic Gene Expression in Male KKAy Mice","authors":"Ning Ma, Yang Xue, Yuxing Tang, Hongxia He, Shanqiang Xu, Xiaohui Yang, Rong Song, Qianqian Yang, Kai Li, Yu Zhao, Huizhen Cai","doi":"10.2337/db25-0845","DOIUrl":"https://doi.org/10.2337/db25-0845","url":null,"abstract":"We investigated whether sustained high-frequency feeding (six meals per day) increases type 2 diabetes mellitus (T2DM) incidence and alters diurnal metabolic patterns in male KKAy mice. Mice were randomly assigned to three or six isocaloric meals per day for 60 days. Metabolic phenotyping, tissue glycogen assays, multitissue circadian clock gene analysis, and exploratory correlation analyses of gene coexpression were performed. Our results demonstrated that high-frequency feeding significantly increased body weight, fasting glucose levels, and T2DM incidence (relative risk = 2.1) compared with three-meal feeding. Six-meal feeding exhibited larger diurnal glucose/insulin oscillations, earlier and higher hepatic glycogen accumulation, disrupted muscle glycogen rhythmicity, and elevated expression of hepatic metabolic genes. Exploratory correlation analyses revealed altered diurnal coexpression patterns among clock and metabolic genes, although causal or regulatory inferences are not warranted from mRNA-level data alone. These findings support meal frequency as an independent modulator of metabolic health and provide preclinical evidence relevant to chrononutrition strategies for T2DM prevention. Article Highlights Meal frequency as an independent determinant of type 2 diabetes mellitus (T2DM) risk under strictly isocaloric conditions remains undefined. We investigated whether increasing meal frequency from three to six isocaloric meals per day alters T2DM incidence and diurnal metabolic and gene expression patterns in male KKAy mice. High-frequency feeding with late-night snacking significantly increased T2DM incidence (relative risk = 2.1), disrupted diurnal glucose and insulin rhythms, increased hepatic glycogen accumulation, and elevated hepatic metabolic gene expression, with altered diurnal coexpression patterns. These findings establish meal frequency as an independent modifier of metabolic health and provide preclinical evidence supporting chrononutrition-based strategies for T2DM prevention.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"31 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148459908","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":"Long-Acting RXR Agonism Preserves Retinal Function and Modulates Inflammation in Diabetic Retinopathy","authors":"Emory Johnson, Ehsan Kaffash, Fadeela Sheini, Ashley Rennhack, Micheli Severo Sielski, Assylbek Zhylkibayev, Sergio L.I. Calzi, Sagun Poudel, Venkatram Atigadda, Qingguo Xu, Maria B. Grant, Marina S. Gorbatyuk","doi":"10.2337/db26-0053","DOIUrl":"https://doi.org/10.2337/db26-0053","url":null,"abstract":"Diabetic retinopathy (DR) is a leading cause of vision loss and is associated with reduced nuclear retinoid X receptor (RXR) activity. Retinal explants exposed to high glucose showed downregulation of RXR, peroxisome proliferator–activated receptor (PPAR), and liver X receptor-β and their lipid metabolism targets (Abca1, Scd1, and Acox1). Supplementation with the RXR agonist UAB126 restored nuclear receptor signaling and preferentially activated RXR/PPAR heterodimers. We evaluated UAB126 microparticles (UAB126-MP), a sustained-release RXR agonist formulation, for pharmacokinetic, molecular, and functional effects in db/db mouse retinas. A single intravitreal injection of UAB126-MP provided extended drug exposure for up to 6 months and increased retinal RXRα expression. Functionally, UAB126-MP preserved scotopic and photopic electroretinographic responses at 2 months and sustained cone photoreceptor function at 6 months. However, it did not reduce acellular capillaries. At 6 months, immunostaining and flow cytometry revealed decreased retinal macrophage/microglial infiltration and reduced CD45-positive myeloid cells and monocytes. These findings indicate that RXR agonism supports neuronal protection and immune modulation but does not prevent vasodegeneration, suggesting primarily neuroprotective and anti-inflammatory actions. Collectively, UAB126-MP confers durable retinal protection through nuclear receptor–mediated pathways, underscoring its potential as a long-acting therapeutic strategy for DR. Article Highlights High glucose exposure of retinal explants reduces expression of nuclear receptors retinoid X receptor (RXR), peroxisome proliferator–activated receptor, and liver X receptor-β, and treatment with UAB126 increases the formation of RXR-peroxisome proliferator–activated receptor heterodimers. Sustained release of UAB126-loaded microparticles enables intravitreal drug delivery for up to 6 months. Intravitreal UAB126 microparticles injection in diabetic mice confers long-term neuroprotection and anti-inflammatory benefits. RXR-targeted therapy represents a promising approach strategy for managing diabetic retinopathy.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"13 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148461860","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":"Ketone Bodies Derived From Medium-Chain Triglycerides Support Brain Metabolism and Function Under Hypoglycemia in Type 1 Diabetes Mellitus","authors":"Domenico Tricò, Lihong Jiang, Daniel Spicer, Kathleen Page, Renata Belfort de Aguiar, Sarita Naik, Mary Savoye, Donna M. Caseria, Jagriti Arora, Graeme F. Mason, Todd Constable, Douglas L. Rothman, Raimund I. Herzog","doi":"10.2337/db26-0293","DOIUrl":"https://doi.org/10.2337/db26-0293","url":null,"abstract":"Impaired cognitive function caused by insulin-induced hypoglycemia is a complication of type 1 diabetes mellitus (T1DM) for which no protective strategies are currently available. In this first-in-human mechanistic study using magnetic resonance spectroscopy, the direct contribution of the infused ketone β-hydroxybutyrate (BHB) to brain metabolism during clamped hypoglycemia was greater in participants with T1DM than healthy participants. In a randomized dietary intervention trial of participants with T1DM and recurrent hypoglycemia, receiving medium-chain triglycerides (MCTs) as a dietary ketone precursor was associated with higher working memory performance and greater regional brain activation during clamped hypoglycemia compared with an isocaloric standard diet. Counterregulatory hormone responses to hypoglycemia were not affected by MCT supplementation. We conclude that ketone bodies are well suited to support brain metabolism in persons with T1DM experiencing insulin-induced hypoglycemia. Dietary MCT supplementation raising BHB may represent a novel strategy to prevent hypoglycemia-induced brain injury in this vulnerable patient population. Article Highlights There are currently no strategies to prevent cognitive impairment caused by insulin-induced hypoglycemia in type 1 diabetes mellitus (T1DM). We examined whether β-hydroxybutyrate (BHB) supports brain metabolism during clamped hypoglycemia and whether dietary medium-chain triglycerides (MCTs), by raising BHB availability, elicit this protective effect. BHB contributed more to brain metabolism in participants with T1DM than in healthy control participants, and long-term MCT supplementation improved working memory and brain activation during hypoglycemia. Dietary MCT supplementation may protect against hypoglycemia-related cognitive deficits in T1DM.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"269 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355676","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":"Targeting the ADA/ADO Axis Rescues β-Cell Failure in Type 2 Diabetes","authors":"Yingxin Zhang, Ning Yu, Rui Fang, Simeng Chen, Xi Xu, Jianfa Zhang","doi":"10.2337/db26-0052","DOIUrl":"https://doi.org/10.2337/db26-0052","url":null,"abstract":"The progressive decline of functional β-cell mass is a hallmark of type 2 diabetes (T2D), yet no current therapies effectively halt this process. While chronic inflammation and metabolic stress contribute to β-cell dysfunction, the key signals integrating these pathways remain elusive. Circulating adenosine deaminase (ADA) elevation in people with diabetes is often viewed as a bystander effect, not a pathogenic component. Here, we show that this elevation reflects a failed compensatory response in a previously unknown purinergic pathway linking dyslipidemia to β-cell failure. Circulating lipids trigger rapid ATP release from erythrocytes, converted to adenosine (ADO). Accumulated ADO drives tissue-specific ADA upregulation in organs affected by diabetes complications, including spleen, kidney, and islets. When this defense fails, toxic ADO selectively causes apoptosis in macrophages, podocytes, and β-cells via defined mechanisms. We show that exogenous ADA performs systemic clearance and local decompression, boosting circulatory adenosine clearance, normalizing tissue ADA hyperactivity, and rescuing islet immunopathology and function. These findings redefine a fundamental pathogenic circuit in T2D and establish the restoration of ADO homeostasis as a therapeutic strategy capable of producing functional β-cell recovery, thereby positioning disease remission as a mechanistically grounded and attainable goal. Article Highlights Challenging the view that elevated circulating adenosine deaminase (ADA) is merely a secondary phenomenon, this study defines its pathogenic role in linking dyslipidemia to β-cell failure and establishes adenosine (ADO) homeostasis restoration as a disease-remitting therapy. We identify tissue-specific compensatory ADA upregulation that paradoxically fails to prevent systemic ADO accumulation, with elevated adenosine selectively inducing apoptosis in immune and pancreatic β-cells. We establish a novel systemic clearance-local decompression therapeutic mechanism in which exogenous ADA reduces circulating ADO, normalizes compensatory tissue ADA hyperactivity, and rescues islet function. This work redefines plasma ADA from a diagnostic marker to a therapeutic target, providing the rationale for an ADA-based therapy that uniquely combines immune modulation with metabolic correction to halt β-cell failure progression.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"62 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148355677","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":"2054-P: Closing the Gap: A Qualitative Study of Provider Perspectives on Barriers to Glycemic Control in the Latinx Population","authors":"DIANA TORRES, SENXI DU, LESLIE NUNEZ, SYLVIA LAMBRECHTS, MATTHEW FREEBY","doi":"10.2337/db26-2054-p","DOIUrl":"https://doi.org/10.2337/db26-2054-p","url":null,"abstract":"Introduction and Objective: Among Latinx patients, diabetes prevalence is high with disproportionately elevated rates of poor glycemic control and diabetes-related complications nationally. Locally, we observe similar disparity gaps in our urban academic medical center, with Latinx patients having worse glycemic control than other groups. This qualitative study aimed to understand provider perspectives on barriers to glycemic control and opportunities to improve diabetes care for this high-risk population. Methods: We conducted nine semi-structured interviews with diabetes care providers across various ambulatory clinics. Interview transcripts were analyzed and coded using qualitative methods to identify common themes and system-level opportunities to improve diabetes care delivery within our health care system. Results: Participants included four endocrinologists, three primary care providers, and two diabetes educators who care for a high volume of Latinx patients with diabetes. Providers described multiple contributors to poor glycemic control, including structural and system-level barriers. Key themes included gaps in culturally tailored education, delays in diabetes education referrals, lack of standardized diabetes resources, and challenges with care coordination. Conclusion: Across interviews, we identified four system-level opportunities to improve diabetes care: (1) culturally tailored education, (2) enhanced integration and promotion of systemwide resources, (3) optimization of the diabetes education referral process, and (4) development of a multidisciplinary support team for high-needs patients. These findings highlight actionable system-level changes that are potentially applicable locally as well as beyond our own institution. We also plan to integrate our findings with patient-voice interviews to ensure future interventions are aligned with patients' needs and reduce disparities in glycemic outcomes. Disclosure D. Torres: None. S. Du: None. L. Nunez: None. S. Lambrechts: None. M. Freeby: Research Support; Ended; Fractyl Health, Inc., Novo Nordisk.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"14 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148286376","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":"2067-P: Effect of Phentermine/Topiramate on BMI Reduction in Adolescents with Youth-Onset Type 2 Diabetes and Obesity","authors":"MEGAN O. BENSIGNOR, REBECCA FREESE, SILVA ARSLANIAN, KYLE RUDSER, AARON S. KELLY","doi":"10.2337/db26-2067-p","DOIUrl":"https://doi.org/10.2337/db26-2067-p","url":null,"abstract":"Introduction and Objective: First-line treatment (metformin ± insulin) for youth-onset type 2 diabetes (Y-T2D) does not reduce elevated adiposity, a primary risk factors for Y-T2D. The objective was to evaluate the effects of phentermine/topiramate (PHEN/TPM) versus placebo on body mass index (BMI) in adolescents with Y-T2D and obesity. Methods: A pilot, randomized 24-week placebo-controlled trial in adolescents, aged 12-20 years, with Y-T2D and obesity was conducted. Participants were randomized 1:1 to placebo or PHEN/TPM, a oral medication FDA-approved for youth ≥ 12 years with obesity. Participants initiated PHEN/TPM at 3.75 mg/23 mg once daily in the morning and increased every 2 weeks to a dose of 15 mg/92 mg after 8 weeks. Participants who were on metformin ± insulin therapy prior to enrollment remained on these medications. Linear regression model with an intent-to-treat population was used to compare the BMI percent change from randomization to week 24 between the groups, adjusted for baseline BMI. Results: Thirteen participants (mean age 15.5 ± 2.1 years, 38.5% female) were randomized. Mean baseline BMI was 40.3 ± 9.57 kg/m2. At the end of 24 weeks, the mean BMI change was -6.4% for those randomized to PHEN/TPM and 0.3% for the placebo group. When adjusted for baseline BMI, the placebo-subtracted BMI reduction was significant (-6.1; 95% CI [-10.93, -1.28]; p=0.019). Conclusion: In this pilot trial, PHEN/TPM significantly reduced BMI in adolescents with T2D diabetes and obesity compared with placebo. PHEN/TPM may be considered as adjuvant therapy for BMI reduction to first-line Y-T2D medications in youth with T2D and obesity. Disclosure M.O. Bensignor: Research Support; Current; Dexcom, Inc., Vivus Inc. R. Freese: None. S. Arslanian: None. K. Rudser: None. A.S. Kelly: Advisory Panel; Current; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk. Research Support; Current; Vivus, Novo Nordisk. Funding NIH NIDDK (DK129721)","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"10 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148286393","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}