Diabetes最新文献_第4页

Comparison of the Effects of SGLT-2i Versus GLP-1RA on Cardiovascular and Renal Outcomes in Patients With Type 2 Diabetes, Based on Baseline Renal Function. 基于基线肾功能的SGLT-2i与GLP-1RA对2型糖尿病患者心血管和肾脏预后影响的比较

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/db24-0688

Yu Wang, Chao Xia, Manna Li, Gaosi Xu

{"title":"Comparison of the Effects of SGLT-2i Versus GLP-1RA on Cardiovascular and Renal Outcomes in Patients With Type 2 Diabetes, Based on Baseline Renal Function.","authors":"Yu Wang, Chao Xia, Manna Li, Gaosi Xu","doi":"10.2337/db24-0688","DOIUrl":"10.2337/db24-0688","url":null,"abstract":"Finding no head-to-head research evaluating the cardiovascular and renal benefits of sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide 1 receptor agonists (GLP-1RA) in patients with type 2 diabetes (T2D) at different baseline renal function, we performed a network meta-analysis to compare the two drugs indirectly. Systematic literature searches were conducted of the PubMed, Cochrane Library, Web of Science, and Embase databases, covering their inception until 7 January 2025. Randomized controlled trials (RCTs) comparing the effects of SGLT-2i and GLP-1RA in T2D with different glomerular filtration rates (eGFRs) were selected. Results were reported as risk ratios (RRs) with corresponding 95% CIs. Finally, 10 RCTs involving 87,334 patients with T2D were included. In patients with an eGFR >90 mL/min/1.73 m2, GLP-1RA exhibited a superior ability to reduce the risk of all-cause death compared with SGLT-2i (RR 0.75; 95% CI 0.58, 0.97), but it was less effective in reducing the risk of renal outcome (RR 1.80; 95% CI 1.15, 2.84) in patients with an eGFR 60-90 mL/min/1.73 m2. Conversely, in patients with eGFR 30-60 and 60-90 mL/min/1.73 m2, GLP-1RA did not show an advantage in reducing the risk of hospitalization for heart failure (RR 1.87 [95% CI 1.15, 3.04] and 1.37 [95% CI 1.05, 1.78], respectively).Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"672-681"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392766","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}

引用次数: 0

Mitochondrial Ceramides and Weight Loss: Unanswered Questions and Future Directions. 线粒体神经酰胺和减肥：未解之谜和未来方向。

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/db25-0148

Adam Astrada

引用次数: 0

Metabolic Dysfunction Associated With Alterations in Gut Microbiota in Adolescents With Obesity. 肥胖青少年肠道菌群改变与代谢功能障碍相关

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/db24-0866

Alessandra Granato, Quin Yuhui Xie, Anthony Wong, Christopher Yau, Rebecca Noseworthy, Tina Chen, Connor Gianetto-Hill, Emma Allen-Vercoe, Cynthia J Guidos, Jill K Hamilton, Jayne S Danska

{"title":"Metabolic Dysfunction Associated With Alterations in Gut Microbiota in Adolescents With Obesity.","authors":"Alessandra Granato, Quin Yuhui Xie, Anthony Wong, Christopher Yau, Rebecca Noseworthy, Tina Chen, Connor Gianetto-Hill, Emma Allen-Vercoe, Cynthia J Guidos, Jill K Hamilton, Jayne S Danska","doi":"10.2337/db24-0866","DOIUrl":"10.2337/db24-0866","url":null,"abstract":"Obesity in childhood is associated with adulthood obesity, type 2 diabetes (T2D), and future metabolic complications. The gut microbiota is a modifier of host metabolic function with altered bacterial composition associated with disease risk. Few studies have investigated the relationships among metabolic disease, inflammation, and the gut microbiota in youth, in whom these connections likely originate. Here, we characterized the gut microbiome of a cohort of 56 adolescents with obesity and without diabetes using fecal DNA sequencing with absolute bacterial quantitation together with immune and metabolic profiling. We observed multi-log order variation in absolute bacterial biomass dependent on host environment and associated with bacterial taxonomic composition based on a nested case-control comparison. Participants with higher biomass displayed a healthier phenotype with higher gut microbiome diversity; lower abundance of taxa associated with inflammation and pathogenicity, such as Escherichia coli; and lower levels of neutrophil activities. Further association analysis revealed sex-dependent variation, with higher levels of insulin resistance, fasting triglycerides, and markers of neutrophil activities in male adolescents with lower bacterial biomass. Together, these results suggest that intestinal bacterial biomass and composition are associated with metabolic and inflammatory dysregulation evident before T2D diagnosis and identify sex differences in microbiome-associated metabolic dysfunction in adolescents with obesity.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"720-733"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143470370","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}

引用次数: 0

Unilateral Primary Aldosteronism Lacking KCNJ5 Somatic Mutations Is Associated With an Elevated Risk of New-Onset Diabetes. 缺乏KCNJ5体细胞突变的单侧原发性醛固酮增多症与新发糖尿病风险升高相关

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/db23-0273

Chieh-Kai Chan, Wei-Shiung Yang, Yen-Hung Lin, Vin-Cent Wu, Jeff S Chueh

{"title":"Unilateral Primary Aldosteronism Lacking KCNJ5 Somatic Mutations Is Associated With an Elevated Risk of New-Onset Diabetes.","authors":"Chieh-Kai Chan, Wei-Shiung Yang, Yen-Hung Lin, Vin-Cent Wu, Jeff S Chueh","doi":"10.2337/db23-0273","DOIUrl":"10.2337/db23-0273","url":null,"abstract":"The association between KCNJ5 mutations and the risk of developing new-onset diabetes (NOD) in patients with unilateral primary aldosteronism (uPA) remains underexplored. To investigate this association, we conducted a longitudinal study using data from the Taiwan Primary Aldosteronism Investigation database. Our sample included 360 patients with uPA who underwent adrenalectomy between 2012 and 2017, 191 (53.1%) of whom had KCNJ5 mutations in their adrenal adenomas. We found that patients with uPA harboring KCNJ5 mutations had a higher rate of complete clinical success (69.5% vs. 43.8%; P < 0.01) and complete biochemical success (93.8% vs. 86.6%; P = 0.04) compared with those without KCNJ5 mutations at 6 months to 1 year after adrenalectomy. Over an average follow-up period of 8.5 years, multivariate Cox regression analysis revealed that patients with uPA with KCNJ5 mutations had a significantly lower risk of developing NOD (hazard ratio [HR] 0.41; 95% CI 0.17-0.996; P = 0.049). Additionally, we identified higher BMI (HR 1.23; 95% CI 1.11-1.37; P < 0.01) and lower estimated glomerular filtration rate (eGFR; HR 0.98; 95% CI 0.97-0.99; P = 0.01) as potential predictors of NOD based on baseline characteristics. The association between patients with uPA without KCNJ5 mutations and higher incidence of NOD was less pronounced in subgroups characterized by younger age, higher BMI, higher eGFR, and lower potassium levels. In conclusion, patients with uPA without KCNJ5 mutations had a higher incidence of NOD, with 13.6% affected during long-term follow-up. Our findings suggest that patients with uPA without KCNJ5 mutations may require more frequent follow-up for NOD after adrenalectomy.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"850-859"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015136/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495109","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Diabetes Spotlight: Kirk Habegger, PhD: The Impact of Glucagon on Metabolic Processes. 糖尿病焦点：Kirk Habegger博士：胰高血糖素对代谢过程的影响。

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/dbi25-0015

Benjamin Page

引用次数: 0

Bend It Like Occam: Ductal Origin of New Islet Cells in Human Pancreas After Injury. 像Occam一样弯曲：人胰腺损伤后新胰岛细胞的导管起源。

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/dbi25-0007

Juan Domínguez-Bendala, Susan Bonner-Weir

引用次数: 0

Canagliflozin-Induced Adaptive Metabolism in Bone. 卡格列净诱导的骨适应性代谢。

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/db24-0955

Sher Bahadur Poudel, Carolyn Chlebek, Ryan R Ruff, Zhiming He, Fangxi Xu, Gozde Yildirim, Bin Hu, Christopher Lawrence De Jesus, Ankita Raja Shinde, Vasudev Vivekanand Nayak, Lukasz Witek, Timothy Bromage, Thomas A Neubert, Clifford J Rosen, Shoshana Yakar

{"title":"Canagliflozin-Induced Adaptive Metabolism in Bone.","authors":"Sher Bahadur Poudel, Carolyn Chlebek, Ryan R Ruff, Zhiming He, Fangxi Xu, Gozde Yildirim, Bin Hu, Christopher Lawrence De Jesus, Ankita Raja Shinde, Vasudev Vivekanand Nayak, Lukasz Witek, Timothy Bromage, Thomas A Neubert, Clifford J Rosen, Shoshana Yakar","doi":"10.2337/db24-0955","DOIUrl":"10.2337/db24-0955","url":null,"abstract":"Sodium-glucose transporter-2 inhibitor (SGLT2i) drugs are widely used for lowering blood glucose levels independent of insulin. Beyond this, these drugs induce various metabolic changes, including weight loss and impaired bone integrity. A significant gap exists in understanding SGLT2i-induced skeletal changes, as SGLT2 is not expressed in osteoblasts or osteocytes, which use glucose to remodel the bone matrix. We studied the impact of 1, 3, or 6 months of canagliflozin (CANA), an SGLT2i treatment, on the skeleton of 6-month-old genetically heterogeneous UM-HET3 mice. Significant metabolic adaptations to CANA were evident as early as 1.5 months after treatment, specifically in male mice. CANA-treated male mice exhibited notable reductions in body weight and decreased proinflammatory and bone remodeling markers associated with reduced cortical bone remodeling indices. Bone tissue metabolome indicated enrichment in metabolites related to amino acid transport and tryptophan catabolism in CANA-treated male mice. In contrast, CANA-treated female mice showed increases in nucleic acid metabolism. An integrOmics approach of source-matched bone tissue metabolome and bone marrow RNA sequencing indicated a positive correlation between the two omics data sets in male mice. Three clusters of transcripts and metabolites involved in energy metabolism, oxidative stress response, and cellular proliferation and differentiation were reduced in CANA-treated male mice. In conclusion, CANA affects bone metabolism mainly via the \"glucose restriction state\" it induces and impacts bone cell proliferation and differentiation. These findings underline the effects of SGLT2i on bone health and highlight the need to consider sex-specific responses when developing clinical treatments that alter substrate availability.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"812-826"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12015145/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CD40 Induces Unfolded Protein Response, Upregulation of VEGF, and Vascular Leakage in Diabetic Retinopathy. Cd40在糖尿病视网膜病变中诱导未折叠蛋白反应、vegf上调和血管渗漏。

Diabetes Pub Date : 2025-05-01 DOI: 10.2337/db23-0538

Sarah Vos, Jose-Andres C Portillo, Alyssa Hubal, Reena Bapputty, Amelia Pfaff, Rachel Aaron, Matthew Weng, Da Sun, Zheng-Rong Lu, Jin-Sang Yu, Carlos S Subauste

{"title":"CD40 Induces Unfolded Protein Response, Upregulation of VEGF, and Vascular Leakage in Diabetic Retinopathy.","authors":"Sarah Vos, Jose-Andres C Portillo, Alyssa Hubal, Reena Bapputty, Amelia Pfaff, Rachel Aaron, Matthew Weng, Da Sun, Zheng-Rong Lu, Jin-Sang Yu, Carlos S Subauste","doi":"10.2337/db23-0538","DOIUrl":"10.2337/db23-0538","url":null,"abstract":"The unfolded protein response (UPR) drives events that promote diabetic retinopathy, including vascular endothelial growth factor (VEGF) upregulation in Müller cells. How UPR is activated in vivo in the diabetic retina is not well understood. CD40 is required for development of diabetic retinopathy, but whether CD40 mediates activation of UPR sensors is unknown. CD40 ligation in Müller cells caused phospholipase Cγ1 (PLCγ1)-dependent activation of UPR sensors (PERK, IRE1α, and ATF6α) and VEGF production dependent on PLCγ1 and UPR sensors. Diabetic Cd40-/- mice did not exhibit UPR activation or VEGF upregulation in the retina. These responses were restored in diabetic Cd40-/- mice rescued to express wild-type CD40 in Müller cells but not in mice rescued to express a CD40 mutation unable to recruit TRAF2/3. Intravitreal administration of a cell-permeable CD40-TRAF2/3-disrupting peptide reduced UPR activation, VEGF upregulation, and vascular leakage in diabetic mice. CD40 and TRAF2 in Müller cells from patients with diabetic retinopathy colocalized with activated UPR sensors and VEGF. Our study indicates that CD40 (via TRAF2/3 signaling) is an inducer of UPR activation that triggers VEGF production in Müller cells. This work uncovered inhibition of CD40-TRAF2/3 signaling as a potential approach to impair UPR activation, VEGF upregulation, and vascular leakage in diabetic retinopathy.Article highlights: ","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":"798-811"},"PeriodicalIF":0.0,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12012590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143461275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Metabolic and paracrine heterogeneity of pancreatic glucagon-secreting α-cells. 胰高血糖素分泌α-细胞的代谢和旁分泌异质性。

Diabetes Pub Date : 2025-04-04 DOI: 10.2337/db24-1053

Haiqiang Dou, Caroline Miranda, Johan Tolö, Cristiano Santos, Rui Gao, Nikhil R Gandasi, Thomas G Hill, Lakshmi Kothegala, Andrei I Tarasov, Quan Zhang, Patrik Rorsman

{"title":"Metabolic and paracrine heterogeneity of pancreatic glucagon-secreting α-cells.","authors":"Haiqiang Dou, Caroline Miranda, Johan Tolö, Cristiano Santos, Rui Gao, Nikhil R Gandasi, Thomas G Hill, Lakshmi Kothegala, Andrei I Tarasov, Quan Zhang, Patrik Rorsman","doi":"10.2337/db24-1053","DOIUrl":"https://doi.org/10.2337/db24-1053","url":null,"abstract":"By stimulating hepatic glucose production, glucagon (released by islet α-cells) restores normal blood glucose levels when they fall below the normal range. We used optogenetics in conjunction with electrophysiology, [Ca2+]i imaging and hormone release measurements to explore the intrinsic and paracrine regulation of glucagon secretion. Many α-cells were spontaneously active at 1mM glucose. However, up to ∼50% of the α- cells were electrically silent. KATP channel blockade, amino acids and somatostatin receptor (SSTR) antagonism restored electrical activity in such α-cells. Termination of optoactivation resulted in KATP channel-dependent (tolbutamide-sensitive) membrane repolarization in active α-cells but long-lasting membrane depolarization and action potential firing in silent α-cells. The latter effect was associated with an increased cytoplasmic ATP:ADP-ratio. Optoactivation or -inhibition of somatostatin-releasing δ- cells inhibits and stimulates electrical activity in adjacent (but not distal) α-cells. There is an inverse relationship between basal glucagon secretion (a measure of the fraction active α-cells) and the relative stimulatory effects of amino acids. We conclude that islet α-cells are functionally heterogenous and that their electrical excitability and glucagon release are determined by K+ channel activity due to variable mosaic of KATP and somatostatin-sensitive K+ channels reflecting metabolic state and proximity to δ-cells, respectively.","PeriodicalId":93977,"journal":{"name":"Diabetes","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782297","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}

引用次数: 0

Clonal Hematopoiesis of Indeterminate Potential and Risk of Microvascular Complications Among Individuals With Type 2 Diabetes: A Cohort Study. 克隆造血在2型糖尿病患者中潜在和微血管并发症风险不确定：一项队列研究

Diabetes Pub Date : 2025-04-01 DOI: 10.2337/db24-0841

Jiahe Wei, Yuefeng Yu, Hanzhang Wu, Yingjun Li, Ningjian Wang, Xiao Tan

引用次数: 0