Diabetes最新文献_第2页

JMJD8 regulates adipocyte hypertrophy through the interaction with Perilipin 2 JMJD8通过与Perilipin 2的相互作用调控脂肪细胞肥大

IF 7.7 1区医学

Diabetes Pub Date : 2025-01-09 DOI: 10.2337/db23-0883

Dongjoo You, Sona Kang

引用次数: 0

High-resolution whole-genome DNA methylation revealed unique signatures of painful diabetic neuropathy 高分辨率全基因组DNA甲基化揭示了疼痛性糖尿病神经病变的独特特征

IF 7.7 1区医学

Diabetes Pub Date : 2025-01-08 DOI: 10.2337/db24-0930

Katarzyna Malgorzata Kwiatkowska, Paolo Garagnani, Massimiliano Bonafé, Maria G. Bacalini, Claudia Sala, Gastone Castellani, Davide Gentilini, Luciano Calzari, Dan Ziegler, Monique M. Gerrits, Catharina G. Faber, Rayaz A. Malik, Margherita Marchi, Erika Salvi, Giuseppe Lauria, Chiara Pirazzini

{"title":"High-resolution whole-genome DNA methylation revealed unique signatures of painful diabetic neuropathy","authors":"Katarzyna Malgorzata Kwiatkowska, Paolo Garagnani, Massimiliano Bonafé, Maria G. Bacalini, Claudia Sala, Gastone Castellani, Davide Gentilini, Luciano Calzari, Dan Ziegler, Monique M. Gerrits, Catharina G. Faber, Rayaz A. Malik, Margherita Marchi, Erika Salvi, Giuseppe Lauria, Chiara Pirazzini","doi":"10.2337/db24-0930","DOIUrl":"https://doi.org/10.2337/db24-0930","url":null,"abstract":"The aim of this work was to describe the DNA methylation signature and to identify genes associated with neuropathic pain in type 2 diabetes mellitus. We analyzed two independent diabetic neuropathy cohorts: PROPGER consisting of 72 painful and 67 painless patients recruited at the German Diabetes Center in Düsseldorf (DE), and PROPENG comprising 27 painful and 65 painless diabetic neuropathy patients recruited at the University of Manchester (UK). Genome-wide methylation data was generated using Illumina Infinium Methylation EPIC v1.0 BeadChip. We used four different selection criteria to identify promising pain-related genes. Our findings revealed significant differences in methylation patterns between painful and painless diabetic neuropathy and identified a set of individual CpG sites of unique candidate genes associated with the painful phenotype. Several of these genes, including GCH1, MYT1L and MED16, have been previously linked to pain-related phenotypes or diabetes. Through pathway enrichment analysis, we demonstrated that specific epigenetic signatures could contribute to the complex phenotype of diabetic neuropathy and cluster analyses highlighted significant epigenetic dissimilarities between painful and painless phenotypes. Our results uncovered epigenetic differences between painful and painless diabetic neuropathy patients and identified targeted genes linked to neuropathic pain through DNA methylation mechanisms. This approach holds promise for investigating other chronic pain conditions, such as secondary chronic pain from cancer treatment, thoracic surgery, and various transplant settings.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"67 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142936938","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}

引用次数: 0

Integrative proteogenomic analyses provide novel interpretations of type 1 diabetes risk loci through circulating proteins 综合蛋白质基因组学分析通过循环蛋白为1型糖尿病风险位点提供了新的解释

IF 7.7 1区医学

Diabetes Pub Date : 2025-01-06 DOI: 10.2337/db24-0380

Tianyuan Lu, Despoina Manousaki, Lei Sun, Andrew D. Paterson

{"title":"Integrative proteogenomic analyses provide novel interpretations of type 1 diabetes risk loci through circulating proteins","authors":"Tianyuan Lu, Despoina Manousaki, Lei Sun, Andrew D. Paterson","doi":"10.2337/db24-0380","DOIUrl":"https://doi.org/10.2337/db24-0380","url":null,"abstract":"Circulating proteins may be promising biomarkers or drug targets. Leveraging genome-wide association studies of type 1 diabetes (18,942 cases and 501,638 controls of European ancestry) and circulating protein abundances (10,708 European ancestry individuals), Mendelian randomization analyses were conducted to assess the associations between circulating abundances of 1,560 candidate proteins and the risk of type 1 diabetes, followed by multiple sensitivity and colocalization analyses, horizontal pleiotropy examinations, and replications. Bulk tissue and single-cell gene expression enrichment analyses were performed to explore candidate tissues and cell types for prioritized proteins. After validating Mendelian randomization assumptions and colocalization evidence, we found that genetically predicted circulating abundances of CTSH (OR=1.17 per one standard deviation increase; 95% CI:1.10-1.24), IL27RA (OR=1.13; 95% CI:1.07-1.19), SIRPG (OR=1.37; 95% CI:1.26-1.49), and PGM1 (OR=1.66; 95% CI:1.40-1.96) were associated with the risk of type 1 diabetes. These findings were consistently replicated in other cohorts. CTSH, IL27RA, and SIRPG were strongly enriched in immune system-related tissues, while PGM1 was enriched in muscle and liver tissues. Amongst immune cells, CTSH was enriched in B cells and myeloid cells, while SIRPG was enriched in T cells and natural killer cells. These proteins may be explored as biomarkers or drug targets for type 1 diabetes.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"35 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934921","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}

引用次数: 0

Effects of metformin on postprandial blood pressure, heart rate, gastric emptying, GLP-1 and the prevalence of postprandial hypotension in type 2 diabetes – a double-blind, placebo-controlled crossover study 二甲双胍对2型糖尿病患者餐后血压、心率、胃排空、GLP-1和餐后低血压患病率的影响——一项双盲、安慰剂对照交叉研究

IF 7.7 1区医学

Diabetes Pub Date : 2025-01-06 DOI: 10.2337/db24-0830

Daniel R. Quast, Cong Xie, Michelle J. Bound, Jacqueline Grivell, Seva Hatzinikolas, Karen L. Jones, Michael Horowitz, Christopher K. Rayner, Michael A. Nauck, Juris J. Meier, Liza K. Phillips, Tongzhi Wu

{"title":"Effects of metformin on postprandial blood pressure, heart rate, gastric emptying, GLP-1 and the prevalence of postprandial hypotension in type 2 diabetes – a double-blind, placebo-controlled crossover study","authors":"Daniel R. Quast, Cong Xie, Michelle J. Bound, Jacqueline Grivell, Seva Hatzinikolas, Karen L. Jones, Michael Horowitz, Christopher K. Rayner, Michael A. Nauck, Juris J. Meier, Liza K. Phillips, Tongzhi Wu","doi":"10.2337/db24-0830","DOIUrl":"https://doi.org/10.2337/db24-0830","url":null,"abstract":"Individuals with type 2 diabetes are at high risk of postprandial falls in blood pressure (BP) (i.e., a reduction in systolic BP of ≥20mmHg, termed postprandial hypotension (PPH)), which increases the risk of falls and mortality. This study evaluated the effects of oral metformin on postprandial BP, heart rate (HR), glucagon-like peptide-1 (GLP-1) and gastric emptying (GE) in individuals with type 2 diabetes. We studied 16 subjects (5 female) before and after ingestion of a 75g radiolabeled glucose drink, after both acute (30 min) and subacute (b.i.d for 7 days) administration of metformin (850mg) or placebo, in a double-blind, randomized, crossover design. 24-hour ambulatory BP measurement following standardized meals (breakfast, lunch and dinner) was used to quantify PPH events. The primary outcome was the postprandial fall in systolic BP. We found that acute administration of metformin did not affect BP, HR, plasma insulin or GLP-1 levels, but slowed GE (P&lt;0.001) and reduced the glycemic response to oral glucose (P&lt;0.001). Sub-acute metformin reduced PPH events by 32% (P=0.035), in association with an increase in HR (P=0.029), slowing of GE (P&lt;0.001), augmentation of plasma GLP-1 (P&lt;0.001), and a reduction in plasma glucose (P&lt;0.001) without affecting plasma insulin. Pre-prandial BP was unaffected by metformin. To conclude, in type 2 diabetes oral metformin attenuates the hypotensive response to meals, associated with stimulation of GLP-1 and slowing of GE to reduce PPH.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"98 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142934922","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}

引用次数: 0

Renal Tubule-Specific Angiotensinogen Deletion Attenuates SGLT2 Expression and Ameliorates Diabetic Kidney Disease in Murine Models of Type 1 Diabetes 肾小管特异性血管紧张素原缺失降低SGLT2表达并改善1型糖尿病小鼠模型中的糖尿病肾病

IF 7.7 1区医学

Diabetes Pub Date : 2025-01-03 DOI: 10.2337/db24-0553

Wen-Xia Yang, Ke Su, Min-Chun Liao, Jing Zhou, Junzheng Peng, Marie-Josée Hébert, Daniel N. Leal, Michifumi Yamashita, Kana N. Miyata, Janos G. Filep, Julie R. Ingelfinger, Shao-Ling Zhang, John S.D. Chan

{"title":"Renal Tubule-Specific Angiotensinogen Deletion Attenuates SGLT2 Expression and Ameliorates Diabetic Kidney Disease in Murine Models of Type 1 Diabetes","authors":"Wen-Xia Yang, Ke Su, Min-Chun Liao, Jing Zhou, Junzheng Peng, Marie-Josée Hébert, Daniel N. Leal, Michifumi Yamashita, Kana N. Miyata, Janos G. Filep, Julie R. Ingelfinger, Shao-Ling Zhang, John S.D. Chan","doi":"10.2337/db24-0553","DOIUrl":"https://doi.org/10.2337/db24-0553","url":null,"abstract":"The role of the intrarenal renin-angiotensin system (iRAS) in diabetic kidney disease (DKD) progression remains unclear. In this study, we generated mice with renal tubule-specific deletion of angiotensinogen (Agt; RT-Agt-/-) in both Akita and streptozotocin (STZ)-induced mouse model of diabetes. Both Akita RT-Agt-/- and STZ-RT-Agt-/- mice exhibited significant attenuation of glomerular hyperfiltration, urinary albumin/creatinine ratio, glomerulomegaly and tubular injury. Urinary Agt, Angiotensin II (Ang II) and oxidative stress were decreased in Akita RT-Agt-/- mice cf. Akita mice. Moreover, thickened glomerular basement membranes, podocyte foot process effacement and podocyte loss were ameliorated in Akita RT-Agt-/- mice cf. Akita mice. Mechanistically, intra-vital microscopy revealed that attenuation of glomerular hyperfiltration in Akita RT-Agt-/- mice was mediated via efferent arteriole (EA) vasodilation and afferent arteriole (AA) vasoconstriction. The AA vasoconstriction was regulated, at least partially, through tubulo-glomerular feedback by down-regulation of sodium-glucose co-transporter 2 (SGLT2) expression in renal proximal tubules. The renal protective effect of iRAS inactivation in Akita RT-Agt-/- mice was more evident than in Akita mice treated with RAS blockers. In vitro, Ang II stimulated, losartan and apocynin inhibited SGLT2 expression in immortalized human renal proximal tubular cells. These findings suggest targeting the iRAS may constitute effective treatment for DKD.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"34 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925005","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}

引用次数: 0

SARS-CoV-2 Spike S1 subunit triggers pericyte and microvascular dysfunction in human pancreatic islets SARS-CoV-2刺突S1亚基触发人胰岛周细胞和微血管功能障碍

IF 7.7 1区医学

Diabetes Pub Date : 2024-12-23 DOI: 10.2337/db24-0816

Catarina Andrade Barboza, Luciana Mateus Gonçalves, Elizabeth Pereira, Roxana Diaz Cruz, Ruy Louzada, Maria Boulina, Joana Almaça

{"title":"SARS-CoV-2 Spike S1 subunit triggers pericyte and microvascular dysfunction in human pancreatic islets","authors":"Catarina Andrade Barboza, Luciana Mateus Gonçalves, Elizabeth Pereira, Roxana Diaz Cruz, Ruy Louzada, Maria Boulina, Joana Almaça","doi":"10.2337/db24-0816","DOIUrl":"https://doi.org/10.2337/db24-0816","url":null,"abstract":"The COVID-19 pandemic has profoundly affected human health, yet the mechanisms underlying its impact on metabolic and vascular systems remain incompletely understood. Clinical evidence suggests that SARS-CoV-2 directly disrupts vascular homeostasis, with perfusion abnormalities observed in various tissues. The pancreatic islet, a key endocrine mini-organ reliant on its microvasculature for optimal function, may be particularly vulnerable. Studies have proposed a link between SARS-CoV-2 infection and islet dysfunction, but the mechanisms remain unclear. Here, we investigated how SARS-CoV-2 spike S1 protein affects human islet microvascular function. Using confocal microscopy and living pancreas slices from non-diabetic organ donors, we show that a SARS-CoV-2 spike S1 recombinant protein activates pericytes — key regulators of islet capillary diameter and beta cell function—and induces capillary constriction. These effects are driven by a loss of angiotensin converting enzyme 2 (ACE2) from pericytes’ plasma membrane, impairing ACE2 activity and increasing local angiotensin II levels. Our findings highlight islet pericyte dysfunction as a potential contributor to the diabetogenic effects of SARS-CoV-2 and offer new insights into the mechanisms linking COVID-19, vascular dysfunction and diabetes.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"32 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879645","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}

引用次数: 0

Extracellular Mitochondria Exacerbate Retinal Pigment Epithelium Degeneration in Diabetic Retinopathy 细胞外线粒体加剧糖尿病视网膜病变视网膜色素上皮变性

IF 7.7 1区医学

Diabetes Pub Date : 2024-12-23 DOI: 10.2337/db24-0040

Keiichi Nishikawa, Tomoaki Murakami, Miyo Yoshida, Noriko Terada, Kenji Ishihara, Yuki Mori, Shinji Ito, Akitaka Tsujikawa

{"title":"Extracellular Mitochondria Exacerbate Retinal Pigment Epithelium Degeneration in Diabetic Retinopathy","authors":"Keiichi Nishikawa, Tomoaki Murakami, Miyo Yoshida, Noriko Terada, Kenji Ishihara, Yuki Mori, Shinji Ito, Akitaka Tsujikawa","doi":"10.2337/db24-0040","DOIUrl":"https://doi.org/10.2337/db24-0040","url":null,"abstract":"Advances in fundus imaging are revealing disruptions in the neurovascular unit in diabetic retinopathy (DR). In the era of anti-VEGF treatment, a thorough characterization of neurodegeneration is imperative until DR patients are sufficiently cured. Here we demonstrate that extracellular mitochondria exacerbate retinal pigment epithelium (RPE) degeneration and inflammation in DR. Extracellular mitochondria increased in the vitreous of DR patients and were associated with visual impairment but not with proliferative diabetic retinopathy or diabetic macular edema. Animal experiments demonstrated detrimental effects of extracellular mitochondria on RPE and photoreceptors. Lysosomal cell death induced by extracellular mitochondria in RPE cells required mitochondrial DNA but not its pattern recognition receptors. Furthermore, biochemical screening identified candidates for DNA receptors. Among them, DNA-dependent protein kinase was necessary for extracellular mitochondria-induced cell death in both in vitro and in vivo experiments. Extracellular mitochondria further induced IL-1β and TNF-α expression in RPE cells in a Toll-like receptor 9 dependent manner. RNA sequencing suggested that extracellular mitochondria exacerbate inflammation by promoting the proliferation and migration of macrophages, at least in part. In summary, extracellular mitochondria are designated as a novel exacerbating factor of RPE degeneration in DR.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"140 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879678","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}

引用次数: 0

Blood-based epigenetic biomarkers associated with incident chronic kidney disease in individuals with type 2 diabetes. 与2型糖尿病患者发生慢性肾病相关的血液表观遗传生物标志物

IF 7.7 1区医学

Diabetes Pub Date : 2024-12-23 DOI: 10.2337/db24-0483

Marian Marchiori, Alice Maguolo, Alexander Perfilyev, Marlena Maziarz, Mats Martinell, Maria F. Gomez, Emma Ahlqvist, Sonia García-Calzón, Charlotte Ling

{"title":"Blood-based epigenetic biomarkers associated with incident chronic kidney disease in individuals with type 2 diabetes.","authors":"Marian Marchiori, Alice Maguolo, Alexander Perfilyev, Marlena Maziarz, Mats Martinell, Maria F. Gomez, Emma Ahlqvist, Sonia García-Calzón, Charlotte Ling","doi":"10.2337/db24-0483","DOIUrl":"https://doi.org/10.2337/db24-0483","url":null,"abstract":"There is an increasing need for new biomarkers improving prediction of chronic kidney disease (CKD) in individuals with type 2 diabetes (T2D). We aimed to identify blood-based epigenetic biomarkers associated with incident CKD and develop a methylation risk score (MRS) predicting CKD in newlydiagnosed individuals with T2D. DNA methylation was analysed epigenome-wide in blood from 487 newly-diagnosed individuals with T2D, of whom 88 developed CKD during 11.5-year follow-up. Weighted Cox regression was used to associate methylation with incident CKD. Weighted logistic models and cross-validation (k=5) were performed to test if the MRS could predict CKD. Methylation at 37 sites was associated with CKD development, based on FDR&lt;5% and absolute methylation differences ≥5% between individuals with incident CKD and those free of CKD during follow-up. Notably, 15 genes annotated to these sites, e.g., TGFBI, SHISA3, and SLC43A2 (encoding LAT4), have been linked to CKD or related risk factors including blood pressure, BMI, or eGFR. Using a MRS including 37 sites and cross-validation for prediction of CKD, we generated ROC curves with AUC=0.82 for the MRS and AUC=0.87 for the combination of MRS and clinical factors. Importantly, ROC curves including the MRS had significantly better AUCs versus the one only including clinical factors (AUC=0.72). The combined epigenetic biomarker had high accuracy in identifying individuals free of future CKD (negative predictive value=94.6%). We discovered a high-performance epigenetic biomarker for predicting CKD, encouraging its potential role in precision medicine, risk stratification, and targeted prevention in T2D.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"35 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142879646","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}

引用次数: 0

Loss of β-cell KATP reduces Ca2+ sensitivity of insulin secretion and Trpm5 expression β-细胞KATP的缺失降低了胰岛素分泌和Trpm5表达的Ca2+敏感性

IF 7.7 1区医学

Diabetes Pub Date : 2024-12-12 DOI: 10.2337/db24-0650

Nathaniel W. York, Zihan Yan, Anna B. Osipovich, Abbie Tate, Sumit Patel, David W. Piston, Mark A. Magnuson, Maria S. Remedi, Colin G. Nichols

{"title":"Loss of β-cell KATP reduces Ca2+ sensitivity of insulin secretion and Trpm5 expression","authors":"Nathaniel W. York, Zihan Yan, Anna B. Osipovich, Abbie Tate, Sumit Patel, David W. Piston, Mark A. Magnuson, Maria S. Remedi, Colin G. Nichols","doi":"10.2337/db24-0650","DOIUrl":"https://doi.org/10.2337/db24-0650","url":null,"abstract":"Loss-of-function (LOF) mutations in KATP channels cause hyperexcitability and insulin hypersecretion, resulting in congenital hyperinsulinism (CHI). Paradoxically, despite the initial insulin hypersecretion, many CHI cases, as well as KATP knockout (KO) animals, eventually ‘crossover’ to undersecretion and even diabetes. Here we confirm that Sur1 KO islets exhibit higher intracellular [Ca2+] ([Ca2+]i) at all [glucose], but show decreased glucose-stimulated insulin secretion. However, when [Ca2+]i is artificially elevated by increasing extracellular [Ca2+], insulin secretion from Sur1 KO islets increases to the same levels as WT islets. This indicates that a right-shift in [Ca2+]i-dependence of insulin secretion, rather than loss of insulin content or intrinsic secretability, is the primary cause for the crossover. Chronic pharmacological inhibition of KATP channel activity by slow release of glibenclamide in pellet-implanted mice causes a very similar ‘crossover’ to glucose intolerance and impaired insulin secretion to that seen in Sur1 KO animals. Whole islet and single cell transcriptomic analysis reveal markedly reduced Trpm5 in both conditions. Glibenclamide pellet-implanted Trpm5 KO mice also exhibited significant glucose intolerance. However, this was not as severe as in WT animals, which suggests that decreased expression of Trpm5 may play a small role in the disruption of insulin secretion with KATP loss.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"11 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142815501","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}

引用次数: 0

Adipose tissue biology and effect of weight loss in women with lipedema 脂肪组织生物学和脂肪水肿妇女减肥的影响

IF 7.7 1区医学

Diabetes Pub Date : 2024-12-09 DOI: 10.2337/db24-0890

Vincenza Cifarelli, Gordon I. Smith, Silvia Gonzalez-Nieves, Dmitri Samovski, Hector H. Palacios, Jun Yoshino, Richard I. Stein, Anja Fuchs, Thomas F. Wright, Samuel Klein

{"title":"Adipose tissue biology and effect of weight loss in women with lipedema","authors":"Vincenza Cifarelli, Gordon I. Smith, Silvia Gonzalez-Nieves, Dmitri Samovski, Hector H. Palacios, Jun Yoshino, Richard I. Stein, Anja Fuchs, Thomas F. Wright, Samuel Klein","doi":"10.2337/db24-0890","DOIUrl":"https://doi.org/10.2337/db24-0890","url":null,"abstract":"Lipedema is a lipodystrophic disease that is typically characterized by a marked increase in lower-body subcutaneous adipose tissue that is purported to have increased inflammation and fibrosis, impaired microvascular/lymphatic circulation and to be resistant to reduction by weight loss therapy. However, these outcomes have not been adequately studied. We evaluated body composition, insulin sensitivity, metabolic health and adipose tissue biology in women with obesity and lipedema (Obese-LIP) before and after moderate (~9%) diet-induced weight loss. At baseline, people with Obese-LIP had ~23% greater leg fat mass, ~11% lower android-to-gynoid ratio and ~48% greater insulin sensitivity (all P&lt;0.05) than women matched on age, BMI and whole-body adiposity. In Obese-LIP, macrophage content and expression of genes involved in inflammation and fibrosis were greater, whereas lymph/angiogenesis-related genes were lower in thigh than abdominal subcutaneous adipose tissue. Weight loss improved insulin sensitivity and decreased total fat mass, with similar relative reductions in abdominal and leg fat masses, but without changes in markers of inflammation and fibrosis. These results demonstrate that affected adipose tissue in women with lipedema is characterized by increased inflammation and fibrogenesis, and alterations in lymphatic and vascular biology. Moderate diet-induced weight loss improves metabolic function and decreases lower-body adipose tissue mass.","PeriodicalId":11376,"journal":{"name":"Diabetes","volume":"37 1","pages":""},"PeriodicalIF":7.7,"publicationDate":"2024-12-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142797021","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}

引用次数: 0