Journal of Diabetes最新文献

{"title":"Long noncoding RNAs and metabolic memory associated with continued progression of diabetic retinopathy","authors":"Jay Kumar,&nbsp;Pooja Malaviya,&nbsp;Renu A. Kowluru","doi":"10.1111/1753-0407.70009","DOIUrl":"https://doi.org/10.1111/1753-0407.70009","url":null,"abstract":"<p>Progression of diabetic retinopathy resists arrest even after institution of intensive glycemic control, suggesting a “metabolic memory” phenomenon, but the mechanism responsible for this phenomenon is still elusive. Gene expression and biological processes can also be regulated by long noncoding RNAs (LncRNAs), the RNAs with &gt;200 nucleotides and no open reading frame for translation, and several LncRNAs are aberrantly expressed in diabetes. Our aim was to identify retinal LncRNAs that fail to reverse after termination of hyperglycemia. Microarray analysis was performed on retinal RNA from streptozotocin-induced diabetic rats in poor glycemic control for 8 months, followed by in good glycemic control (blood glucose &gt;400 mg/dL), or for 4 months, with four additional months of good glycemic control (blood glucose &lt;150 mg/dL). Differentially expressed LncRNAs and mRNAs were identified through Volcano filtering, and their functions were predicted using gene ontology and pathway enrichment analyses. Compared with age-matched normal rats, rats in continuous poor glycemic control had &gt;1479 differentially expressed LncRNAs (710 downregulated, 769 upregulated), and among those, 511 common LncRNAs had similar expression in Diab and Rev groups (139 downregulated, 372 upregulated). Gene Ontology/pathway analysis identified limited LncRNAs in biological processes, but analysis based on biological processes/molecular function revealed &gt;350 genes with similar expression in Diab and Rev groups; these genes were mainly associated with stress response, cell death, mitochondrial damage and cytokine production. Thus, identifying retinal LncRNAs and their gene targets that do not benefit from termination of hyperglycemia have potential to serve as therapeutic targets to slow down the progression of diabetic retinopathy.</p><p>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/1753-0407.70009","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142665908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subcellular mass spectrometric detection unveils hyperglycemic memory in the diabetic heart","authors":"Jiabing Zhan,&nbsp;Yufei Zhou,&nbsp;Yifan Chen,&nbsp;Kunying Jin,&nbsp;Zhaoyang Chen,&nbsp;Chen Chen,&nbsp;Huaping Li,&nbsp;Dao Wen Wang","doi":"10.1111/1753-0407.70033","DOIUrl":"10.1111/1753-0407.70033","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Intensive glycemic control is insufficient to reduce the risk of heart failure in patients with diabetes mellitus. While the hyperglycemic memory in the diabetic cardiomyopathy has been well documented, its underlying mechanisms are not fully understood. The present study tried to investigate whether the dysregulated proteins/biological pathways, which persistently altered in diabetic hearts during normoglycemia, participate in the hyperglycemic memory.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Hearts of streptozotocin-induced diabetic mice, with or without intensive glycemic control using slow-release insulin implants, were collected. Proteins from total heart samples and subcellular fractions were assessed by mass spectrometry, Western blotting, and KEGG pathway enrichment analysis. mRNA sequencing was used to determine whether the persistently altered proteins were regulated at the transcriptional or post-transcriptional level.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Western blot validation of several proteins with high pathophysiological importance, including MYH7, HMGCS2, PDK4, and BDH1, indicated that mass spectrometry was able to qualitatively, but not quantitatively, reflect the fold changes of certain proteins in diabetes. Pathway analysis revealed that the peroxisome, PPAR pathway, and fatty acid metabolism could be efficiently rescued by glycemic control. However, dysregulation of oxidative phosphorylation and reactive oxygen species persisted even after normalization of hyperglycemia. Notably, mRNA sequencing revealed that dysregulated proteins in the oxidative phosphorylation pathway were not accompanied by coordinated changes in mRNA levels, indicating post-transcriptional regulation. Moreover, literature review and bioinformatics analysis suggested that hyperglycemia-induced persistent alterations of miRNAs targeted genes from the persistently dysregulated oxidative phosphorylation pathway, whereas, oxidative phosphorylation dysfunction-induced ROS regulated miRNA expression, which thereby might sustained the dysregulation of miRNAs.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusions&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Glycemic control cannot rescue hyperglycemia-induced alterations of subcellular proteins in the diabetic heart, and persistently altered proteins are involved in multiple functional pathways, including oxidative phosphorylation. These findings might provide novel insights into hyperglycemic memory in diabetic cardiomyopathy.&lt;/p&gt;\u0000 \u0000 &lt;div&gt;\u0000 &lt;figure&gt;\u0000 ","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11561303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structural and functional alterations of the hippocampal subfields in T2DM with mild cognitive impairment and insulin resistance: A prospective study","authors":"Chen Yang,&nbsp;Huiyan Zhang,&nbsp;Zihan Ma,&nbsp;Yanjun Fan,&nbsp;Yanan Xu,&nbsp;Jian Tan,&nbsp;Jing Tian,&nbsp;Jiancang Cao,&nbsp;Wenwen Zhang,&nbsp;Gang Huang,&nbsp;Lianping Zhao","doi":"10.1111/1753-0407.70029","DOIUrl":"10.1111/1753-0407.70029","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance (IR) and is often accompanied by mild cognitive impairment (MCI). The detrimental effects of T2DM and IR on the hippocampus have been extensively demonstrated. Few studies have examined the effects of IR on structure and function of hippocampal subfields in T2DM-MCI patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Method</h3>\u0000 \u0000 <p>A total of 104 T2DM patients were recruited in this prospective study and divided into four groups (T2DM-MCI-higherIR, <i>n</i> = 17; T2DM-MCI-lowerIR, <i>n</i> = 32; T2DM-nonMCI-higherIR, <i>n</i> = 19; T2DM-nonMCI-lowerIR, <i>n</i> = 36). Structure and function MRI data were captured. Clinical variables and neuropsychological scores were determined for all participants. Hippocampal subfield volume and functional connectivity were compared among four groups. Partial correlation analysis was performed between imaging indicators, clinical variables, and neuropsychological scores in all patients.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>T2DM-MCI-higher IR group had the smallest volumes of bilateral hippocampal tail, right subiculum-body, right GC-ML-DG-body, and right CA4-body. IR in right hippocampal tail, right subiculum-body, and right GC-ML-DG-body exerted main effect. Furthermore, elevated functional connectivity was found between right subiculum-body and bilateral dorsolateral prefrontal cortex and right anterior cingulate–medial prefrontal cortex. Hippocampal subfield volume positively correlates with total cholesterol and triglycerides and negatively correlates with fasting insulin.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The present study found that T2DM-MCI patients have structural and functional alterations in hippocampal subfields, and IR is a negative factor influencing the alteration of hippocampal subfields volume. These findings support the importance of IR in T2DM-MCI patients and might be potential neuroimaging biomarkers of cerebral impairment in T2DM-MCI patients.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of maternal serum ferritin levels across gestation with gestational diabetes mellitus: A longitudinal cohort study","authors":"Huiqin Mo,&nbsp;Jingna Wen,&nbsp;Cuicui Qu,&nbsp;Xiaohua Liu","doi":"10.1111/1753-0407.70027","DOIUrl":"10.1111/1753-0407.70027","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The longitudinal changes in maternal serum ferritin (SF) levels across gestation, which indirectly reflect iron supplementation, have not been extensively investigated in relation to gestational diabetes mellitus (GDM).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We conducted a retrospective cohort study at a tertiary maternal hospital in Shanghai. Women with SF concentration measurements at 8.0–13.6 weeks' gestation (GW), 29.0–31.6 GW, and an oral glucose tolerance test (OGTT) at 24–28 GW were included. We utilized logistic regression analysis to assess GDM association with maternal SF levels and longitudinal changes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The study included 17 560 women, with 2160 (12.3%) participants diagnosed with GDM. Adjusted odds ratios (ORs) (95% confidence intervals [CIs]) for GDM across increasing quartiles of SF concentrations at 8.0–13.6 GW were 1.00 (reference), 1.139 (95% CI: 1.012–1.283), 1.093 (95% CI: 0.969–1.233), and 1.248 (95% CI: 1.111–1.403). Similarly, at 29.0–31.6 GW, increasing quartiles of SF concentrations were associated with higher adjusted ORs for GDM: 1.00 (reference), 1.165 (95% CI: 1.029–1.320), 1.335 (95% CI: 1.184–1.505), and 1.428 (95% CI: 1.268–1.607). Pregnant women with higher SF levels (upper 25th percentile) at 8.0–13.6 GW had a reduced GDM risk if their SF levels decreased to the lower 25th percentile at 29.0–31.6 GW. Conversely, the subgroup with higher SF levels (upper 25th percentile) at both time points had the highest incidence rate of GDM (15.3%, 1.235 [95% CI: 1.087–1.404]).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Maternal SF levels independently and positively associated with GDM risk during early and late gestational stages. Considering the increased GDM risk, routine iron supplementation for iron-replete women is questionable.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11551590/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences of visceral fat with cardiac structure and function in type 2 diabetes: A cross-sectional study","authors":"Chen Rui-hua,&nbsp;Lin Yi,&nbsp;Xu Huan-bai,&nbsp;Wang Yu-fan,&nbsp;Peng Yong-de","doi":"10.1111/1753-0407.70023","DOIUrl":"10.1111/1753-0407.70023","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The aim of this study is to analyze the associations among fat distribution, left ventricular (LV) structure, and function in T2DM patients and further assess the sex differences among them.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Two thousand and one hundred seven T2DM patients were enrolled to this study. Patients' height, weight, BMI, visceral fat area (VFA), baPWV, parameters of cardiac structure and function, and clinical biochemical indicators were measured and collected.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>There were significant differences between male and female T2DM patients in age, duration of diabetes, complication ratio of hypertension and dyslipidemia, smoking history, visceral fat, baPWV, and ventricular structure and function (<i>p</i> &lt; 0.05). Compared with the Q1 group, female patients in the highest quartile (Q4) of VFA had a decreased LVEF and significantly increased baPWV (<i>p</i> &lt; 0.05), whereas no such changes were found in males. The correlation analysis showed that LVEF in male patients was negatively correlated with hypertension history, using of CCBs, GLP-1RA, lipid-lowering medications, BMI, WC, WHR, FPG, FC-P, HbA1c, GA, HOMA-IR, Cr, and baPWV, while the LVEF in female patients was negatively correlated with VFA, VSR, VFA/BMI, VFA/H², VFA/weight in females (<i>p</i> &lt; 0.05). LVMI was positively associated with diabetes duration, age, hypertension history, WC, WHR, VFA, SFA, VFA/BMI, VFA/H², VFA/weight, and baPWV in both males and females. Multivariable-adjusted linear regression analysis showed that VFA was independently associated with LVEF (<i>β</i> = − 0.096, <i>p</i> = 0.010), LVMI (<i>β</i> = 0.083, <i>p</i> = 0.038), and baPWV (<i>β</i> = 0.120, <i>p</i> = 0.003) in females.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Values of VFA were independently associated with LVEF, LVMI, and baPWV in women, but not in men, in patients with T2DM.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544034/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical characteristics, treatment, and treatment switch after molecular-genetic classification in individuals with maturity-onset diabetes of the young: Insights from the multicenter real-world DPV registry","authors":"Stefanie Lanzinger,&nbsp;Katharina Laubner,&nbsp;Katharina Warncke,&nbsp;Julia K. Mader,&nbsp;Sebastian Kummer,&nbsp;Claudia Boettcher,&nbsp;Torben Biester,&nbsp;Angela Galler,&nbsp;Daniela Klose,&nbsp;Reinhard W. Holl","doi":"10.1111/1753-0407.70028","DOIUrl":"10.1111/1753-0407.70028","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Individuals with maturity-onset diabetes of the young (MODY) are often misdiagnosed as type 1 or type 2 diabetes and receive inappropriate care. We aimed to investigate the characteristics and treatment of all MODY types in a multicenter, real-world setting.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Individuals with MODY from the diabetes prospective follow-up (DPV) registry were studied. We compared clinical parameters during the first year of diabetes and the most recent treatment year after MODY diagnosis.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A total of 1640 individuals were identified with <i>GCK</i>-MODY (<i>n</i> = 941) and <i>HNF1A</i>-MODY (<i>n</i> = 417) as the most frequent types. Among these, 912 individuals were available with information during the first and the most recent treatment year (median duration of follow-up: 4.2 years [2.6–6.6]). Positive beta cell autoantibodies were present in 20.6% (15.2% IAA). Median age at diagnosis ranged from 9.9 years in <i>GCK</i>-MODY (Q1–Q3: 6.2–13.1 years) and <i>INS</i>-MODY (2.7–13.7 years) to 14.3 years (5.0–17.1) in <i>KCNJ11</i>-MODY. Frequency of oral antidiabetic agents (OAD) use increased and insulin decreased in <i>HNF4A</i>-MODY (OAD: 18% to 39%, insulin: 34% to 23%) and in <i>HNF1A</i>-MODY (OAD: 18% to 31%, insulin: 35% to 25%). <i>ABCC8</i>-MODY was characterized by a decrement in nonpharmacological treatment (26% to 16%) and “insulin only” treatment (53% to 42%), while the proportion of individuals treated with OAD but no insulin increased from 0% to 21%.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Our results indicate that some teams caring for individuals with MODY are hesitant with regard to current recommendations. Registries are an essential source of information and provide a basis for discussing treatment guidelines for MODY.</p>\u0000 \u0000 <div>\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </div>\u0000 </section>\u0000 </div>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544032/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142602633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"β-Cell gene expression stress signatures in types 1 and 2 diabetes","authors":"Xiaoyan Yi,&nbsp;Decio L. Eizirik","doi":"10.1111/1753-0407.70026","DOIUrl":"10.1111/1753-0407.70026","url":null,"abstract":"&lt;p&gt;Diabetes mellitus (DM) is a chronic metabolic disorder that occurs when pancreatic β-cells can no longer produce enough insulin to maintain normal blood glucose levels. DM presently affects 10.5% of the world adult population. While T1D is a disease of “mistaken identity,” where the immune system attacks and destroys pancreatic β-cells in the context of islet inflammation (insulitis),&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; T2D is associated with sedentary lifestyles and high-fat diets, typically involving ineffective use of insulin and progressive loss of β-cell function.&lt;span&gt;&lt;sup&gt;1&lt;/sup&gt;&lt;/span&gt; Both diseases result from multifaceted interactions between genetic and environmental factors, with β-cell failure as the core mechanism of pathogenesis.&lt;/p&gt;&lt;p&gt;In T1D, the disease arises from a complex interaction between immune cells and β-cells, involving chemokine and cytokine release and signals from stressed or dying β-cells that attract and activate immune cells to the islets and lead to β-cell apoptosis.&lt;span&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/span&gt; Beyond the destruction of β-cells by the immune system, it is now accepted that stress and impaired function of these cells significantly contribute to the onset and progression of the disease.&lt;span&gt;&lt;sup&gt;1-3&lt;/sup&gt;&lt;/span&gt; In T2D, the disease is driven by an interplay between insulin resistance and β-cell dysfunction in genetically susceptible individuals, with metabolic stress and perhaps also inflammation impairing insulin secretion and eventually β-cell survival, although to a less degree than in T1D.&lt;span&gt;&lt;sup&gt;1, 4, 5&lt;/sup&gt;&lt;/span&gt;&lt;/p&gt;&lt;p&gt;The complexity of diabetes pathogenesis makes it very difficult to identify specific causes of the disease, which hampers the development of adequate therapies to protect β-cells and thus prevent disease. This difficulty was well described by Tolstoy, in his masterpiece “War and Peace,” published 1869 (in this case addressing the Napoleonic war against tsarist Russia): “…the impulse to seek causes is innate in the soul of man. And the human intellect, with no inkling on the immense variety and complexity of circumstances conditioning a phenomena, any one of which may be separately conceived of as the cause of it, snatches the first and most easily understood approximation, and says here is the cause.” In the context of pathophysiology, this had led to the simplistic view of “one gene, one protein, one disease.” However, with the sequencing of the human genome and the subsequent advent of omics technologies that allow interrogating the whole system in a parallel and often also in a sequential way, our understanding of complex diseases changed: we now focus on the dysfunction of gene and transcription factor networks and of post-transcriptional and post-translational mechanisms.&lt;/p&gt;&lt;p&gt;The advent of single-cell RNA sequencing (scRNA-seq) has provided a new tool for dissecting the molecular intricacies underlying pancreatic islet cells stress and thus addressing mechanisms of disease closer to its real ","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 11","pages":""},"PeriodicalIF":3.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11540585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long noncoding RNAs and metabolic memory associated with continued progression of diabetic retinopathy.","authors":"Jay Kumar, Pooja Malaviya, Renu A Kowluru","doi":"10.1111/1753-0407.70009","DOIUrl":"https://doi.org/10.1111/1753-0407.70009","url":null,"abstract":"<p><p>Progression of diabetic retinopathy resists arrest even after institution of intensive glycemic control, suggesting a \"metabolic memory\" phenomenon, but the mechanism responsible for this phenomenon is still elusive. Gene expression and biological processes can also be regulated by long noncoding RNAs (LncRNAs), the RNAs with >200 nucleotides and no open reading frame for translation, and several LncRNAs are aberrantly expressed in diabetes. Our aim was to identify retinal LncRNAs that fail to reverse after termination of hyperglycemia. Microarray analysis was performed on retinal RNA from streptozotocin-induced diabetic rats in poor glycemic control for 8 months, followed by in good glycemic control (blood glucose >400 mg/dL), or for 4 months, with four additional months of good glycemic control (blood glucose <150 mg/dL). Differentially expressed LncRNAs and mRNAs were identified through Volcano filtering, and their functions were predicted using gene ontology and pathway enrichment analyses. Compared with age-matched normal rats, rats in continuous poor glycemic control had >1479 differentially expressed LncRNAs (710 downregulated, 769 upregulated), and among those, 511 common LncRNAs had similar expression in Diab and Rev groups (139 downregulated, 372 upregulated). Gene Ontology/pathway analysis identified limited LncRNAs in biological processes, but analysis based on biological processes/molecular function revealed >350 genes with similar expression in Diab and Rev groups; these genes were mainly associated with stress response, cell death, mitochondrial damage and cytokine production. Thus, identifying retinal LncRNAs and their gene targets that do not benefit from termination of hyperglycemia have potential to serve as therapeutic targets to slow down the progression of diabetic retinopathy.</p>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":"16 11","pages":"e70009"},"PeriodicalIF":3.0,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142666556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early weight gain after diagnosis may have an impact on remission status in children with new-onset type 1 diabetes mellitus.","authors":"Dicle Canoruc Emet, Hande Nur Karavar, Onur Gozmen, Arife Aslan Agyar, Yağmur Ünsal, Merve Canturk, Pınar Cengiz, Dogus Vuralli, Z Alev Ozon, E Nazlı Gonc","doi":"10.1111/1753-0407.13455","DOIUrl":"10.1111/1753-0407.13455","url":null,"abstract":"<p><strong>Background: </strong>Residual beta-cell function and improvement in insulin sensitivity by reversal of glucose toxicity are two phenomena thought to be related to partial remission (PR). Body fat mass is the major determinant of insulin sensitivity. The aim of this study is to investigate the relationship between the rate of body weight gain after diagnosis of type 1 diabetes mellitus (T1DM) and other clinical factors for the development and duration of PR.</p><p><strong>Methods: </strong>Children (2-16 years) with new-onset T1DM (n = 99) were grouped into remitters and non-remitters by using insulin dose-adjusted glycosylated hemoglobin (HbA1c) values. Laboratory and clinical data as well as daily insulin requirement per kilogram of body weight at diagnosis and each visit were recorded, and the duration of PR was determined. Changes in body mass index standard deviation score (BMI-SDS) were calculated by the auxological data collected every 6 months.</p><p><strong>Results: </strong>There were 47 remitters (47.5%) and 52 (52.5%) non-remitters. The mean increase in BMI-SDS at the first 6 months of diagnosis was higher in the non-remitters than in the remitters (p = 0.04). Duration of PR was negatively correlated with the change in BMI-SDS between 6 and 12 months after diagnosis. Male sex, younger age, prepubertal status, and lower HbA1c were predictors of remission, among which male sex had the highest chance by multivariate regression.</p><p><strong>Conclusions: </strong>Early rapid weight gain after diagnosis of T1DM may play a role in the lack of remission and shorter duration of PR. Interventions to prevent early rapid weight gain can maintain the development and prolongation of remission.</p>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":" ","pages":"1011-1019"},"PeriodicalIF":4.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10755610/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9979345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decreased in n-3 DHA enriched triacylglycerol in small extracellular vesicles of diabetic patients with cardiac dysfunction.","authors":"Wei Ding, Xuejuan Zhang, Dandan Xiao, Wenguang Chang","doi":"10.1111/1753-0407.13457","DOIUrl":"10.1111/1753-0407.13457","url":null,"abstract":"<p><strong>Purpose: </strong>Diabetic cardiomyopathy is the leading cause of death in diabetic patients, and the mechanism by which factors other than hyperglycemia contribute to the development of diabetic cardiomyopathy is unknown. Serum small extracellular vesicles (sEVs) carry bioactive proteins or nuclei, which enter into remote tissues and modulate cell functions. However, in diabetic conditions, the changes of lipids carried by sEVs has not been identified. Our study aims to explore the changes of lipids in sEVs in diabetic patients with cardiovascular disease, we hope to provide new ideas for understanding the role of lipid metabolism in the pathogenesis of diabetic cardiomyopathy.</p><p><strong>Methods: </strong>SEVs samples derived from serum of health controls (Ctrl), diabetic patients without cardiovascular diseases (DM), and diabetic patients with cardiovascular diseases (DM-CAD) were used for lipidomics analysis. Because AC16 cells are also treated with those sEVs to confirm the entrance of cells and effects on insulin sensitivity, a lipidomics analysis on cells was also performed.</p><p><strong>Results and conclusions: </strong>In this study, we found that docosahexaenoic acid (DHA)-triacylglycerides of sEVs from serums of DM-CAD patients decreased significantly, and those sEVs could enter into AC16 cells and diminish insulin sensitivity. In addition, DHA-triacylglycerides were also decreased in cells treated with sEVs from DM-CAD. Therefore, DHA-triacylglycerides carried by sEVs may mediate intercellular signaling and be associated with the incidence of diabetic cardiovascular complications.</p>","PeriodicalId":189,"journal":{"name":"Journal of Diabetes","volume":" ","pages":"1070-1080"},"PeriodicalIF":4.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10755605/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10396737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}