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Cited by 80Diabetes Treatment and ManagementDiabetes Management and ResearchChronic Kidney Disease and Diabetes

Diabetes and its complications: molecular mechanisms, prevention and treatment

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Zhao, Lijun, Yuan, Jiamin, Yang, Qing, Ma, Jing, Yang, Fenghao, Zou, Yutong, Liu, Ke, Liu, Fang·2026·Signal Transduction and Targeted Therapy
DOI 10.1038/s41392-025-02401-wPMC PMC12812840
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Abstract

Diabetic complications represent a formidable clinical challenge characterized by hyperglycemia-induced multiorgan dysfunction and dysregulated intercellular signaling networks. Advances in spatial multiomics and single-cell transcriptomic techniques, along with insights into aberrant signaling via myokines, cytokines, hormones, the gut microbiota, and exosomes, have revealed the molecular heterogeneity and dynamic inter-organ crosstalk underlying diabetes. Digital diabetes prevention programs have demonstrated effectiveness in high-risk populations through the use of remote tools to support lifestyle changes, reduce hemoglobin A1c, and delay the onset of type 2 diabetes. The therapeutic landscape for diabetic complications has been reshaped by agents with proven cardiorenal benefits, including sodium‒glucose cotransporter 2 inhibitors, glucagon‒like peptide-1 receptor agonists, and nonsteroidal mineralocorticoid receptor antagonists, with combination therapies offering potential additive or synergistic effects. However, their optimal application requires careful benefit-risk assessment across diverse patient populations. Novel therapeutic strategies involving mesenchymal stem cells and their derived exosomes, gut microbiota modulation, bioactive compounds from traditional Chinese medicine, and AI-assisted disease management systems offer promising approaches to correct molecular dysfunctions. This review summarizes recent advances in the mechanisms, prevention, and treatment of diabetic complications, alongside a critical examination of current bottlenecks in translational applications. The remaining challenges include establishing long-term safe regenerative therapies and effectively integrating AI into clinical workflows. Although AI shows promise, issues such as limited data diversity and low model interpretability hinder its generalizability and clinical trust. Addressing these challenges will be essential for transitioning toward a proactive, personalized, and patient-centered model of care.

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  • Pathological HIF activation plays a key role in diabetic complications including nephropathy, retinopathy, and impaired wound healing, largely by driving aberrant angiogenesis, fibrosis, and vascular dysfunction.

    “In parallel, pathological HIF activation plays a key role in diabetic complications, including nephropathy, retinopathy, and impaired wound healing, largely by driving aberrant angiogenesis, fibrosis, and vascular dysfunction in hypoxic and inflamed tissues [26,232,247].”

    From HIF inhibition: Current strategies and clinical challenges (2026) · cites this paper as [247]

    The diabetic retinopathy section links hypoxia-induced endothelial activation to pathological neovascularization, and the diabetic kidney disease section describes abnormal angiogenesis, fibrosis, and vascular dysfunction (page numbers unavailable). These passages support some of the complications and mechanisms named, but they do not attribute them to pathological HIF activation or address HIF-driven impaired wound healing. (LLM, conf=0.84)

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  1. [1]American Diabetes, A. Diagnosis and classification of diabetes mellitus. Diabetes Care 34, S62–S69 (2011). 21193628 PMC3006051 · DOI
  2. [4]Chan, J. C. N. et al. The Lancet Commission on diabetes: using data to transform diabetes care and patient lives. Lancet 396, 2019–2082 (2021). 33189186 · DOI · Paper page
  3. [5]Zhang, X., Zhang, J., Ren, Y., Sun, R. & Zhai, X. Unveiling the pathogenesis and therapeutic approaches for diabetic nephropathy: insights from panvascular diseases. Front Endocrinol. 15, 1368481 (2024). PMC10918691 38455648 · DOI
  4. [6]Yu, M. G. et al. Protective factors and the pathogenesis of complications in diabetes. Endocr. Rev. 45, 227–252 (2024). 37638875 PMC10911956 · DOI
  5. [7]Jia, W. et al. Standards of medical care for type 2 diabetes in China 2019. Diabetes Metab. Res Rev. 35, e3158 (2019). 30908791 · DOI
  6. [9]Cole, J. B. & Florez, J. C. Genetics of diabetes mellitus and diabetes complications. Nat. Rev. Nephrol. 16, 377–390 (2020). 32398868 PMC9639302 · DOI · Paper page
  7. [10]Abel, E. D. et al. Diabetes mellitus-Progress and opportunities in the evolving epidemic. Cell 187, 3789–3820 (2024). 39059357 PMC11299851 · DOI
  8. [11]Hsu, P. D., Lander, E. S. & Zhang, F. Development and applications of CRISPR-Cas9 for genome engineering. Cell 157, 1262–1278 (2014). 24906146 PMC4343198 · DOI · Paper page
  9. [12]Gerace, D. et al. CRISPR-targeted genome editing of mesenchymal stem cell-derived therapies for type 1 diabetes: a path to clinical success?. Stem Cell Res Ther. 8, 62 (2017). 28279194 PMC5345178 · DOI
  10. [13]El Nahas, R., Al-Aghbar, M. A., Herrero, L., van Panhuys, N. & Espino-Guarch, M. Applications of genome-editing technologies for type 1 diabetes. Int. J. Mol. Sci. 25, (2023). PMC10778854 38203514
  11. [14]Xu, Y. et al. LINC MIR503HG Controls SC-beta Cell differentiation and insulin production by targeting CDH1 and HES1. Adv. Sci. 11, e2305631 (2024). PMC10987150 38243869 · DOI
  12. [15]Ma, Q. et al. ZnT8 loss-of-function accelerates functional maturation of hESC-derived beta cells and resists metabolic stress in diabetes. Nat. Commun. 13, 4142 (2022). 35842441 PMC9288460 · DOI
  13. [16]Defronzo, R. A. Banting Lecture. From the triumvirate to the ominous octet: a new paradigm for the treatment of type 2 diabetes mellitus. Diabetes 58, 773–795 (2009). 19336687 PMC2661582 · DOI · Paper page
  14. [18]Yazdani, S. et al. Dynamic glucose uptake, storage, and release by human microvascular endothelial cells. Mol. Biol. Cell 33, ar106 (2022). 35921166 PMC9635305 · DOI
  15. [19]Zhang, Z. Y. et al. Molecular mechanisms of glucose fluctuations on diabetic complications. Front Endocrinol. 10, 640 (2019). PMC6759481 31620092 · DOI
  16. [20]Srivastava, S. P. et al. Endothelial SIRT3 regulates myofibroblast metabolic shifts in diabetic kidneys. iScience 24, 102390 (2021). 33981977 PMC8086030 · DOI
  17. [21]Hou, Y. et al. Mitochondrial oxidative damage reprograms lipid metabolism of renal tubular epithelial cells in the diabetic kidney. Cell Mol. Life Sci. 81, 23 (2024). 38200266 PMC10781825 · DOI
  18. [22]Liao, Y. L., Fang, Y. F., Sun, J. X. & Dou, G. R. Senescent endothelial cells: a potential target for diabetic retinopathy. Angiogenesis 27, 663–679 (2024). 39215875 PMC11564237 · DOI
  19. [23]Liu, Y. et al. Mitochondria-associated endoplasmic reticulum membrane (MAM): a dark horse for diabetic cardiomyopathy treatment. Cell Death Discov. 10, 148 (2024). 38509100 PMC10954771 · DOI
  20. [24]Zhang, Y. et al. Synergistic mechanism between the endoplasmic reticulum and mitochondria and their crosstalk with other organelles. Cell Death Discov. 9, 51 (2023). 36759598 PMC9911404 · DOI
  21. [25]Zhao, W. B. & Sheng, R. The correlation between mitochondria-associated endoplasmic reticulum membranes (MAMs) and Ca(2+) transport in the pathogenesis of diseases. Acta Pharm. Sin. 46, 271–291 (2025). PMC11756407 39117969 · DOI
  22. [26]Kelley, N., Jeltema, D., Duan, Y. & He, Y. The NLRP3 inflammasome: an overview of mechanisms of activation and regulation. Int. J. Mol. Sci. 20, 3328 (2019). PMC6651423 31284572
  23. [27]Tai, G. J. et al. NLRP3 inflammasome-mediated premature immunosenescence drives diabetic vascular aging dependent on the induction of perivascular adipose tissue dysfunction. Cardiovasc Res 121, 77–96 (2025). 38643484 · DOI
  24. [28]Wu, M. et al. Inhibition of NLRP3 inflammasome ameliorates podocyte damage by suppressing lipid accumulation in diabetic nephropathy. Metabolism 118, 154748 (2021). 33675822 · DOI
  25. [29]Lv, D. et al. Targeting phenylpyruvate restrains excessive NLRP3 inflammasome activation and pathological inflammation in diabetic wound healing. Cell Rep. Med 4, 101129 (2023). 37480849 PMC10439185 · DOI
  26. [30]Li, C. et al. Macrophage M1 regulatory diabetic nephropathy is mediated by m6A methylation modification of lncRNA expression. Mol. Immunol. 144, 16–25 (2022). 35168108 · DOI
  27. [31]Schiffrin, E. L. & Pollock, D. M. Endothelin system in hypertension and chronic kidney disease. Hypertension 81, 691–701 (2024). 38059359 PMC10954415 · DOI
  28. [32]Davenport, A. P. et al. Endothelin. Pharm. Rev. 68, 357–418 (2016). 26956245 PMC4815360 · DOI · Paper page
  29. [33]van Raalte, D. H. et al. Combination therapy for kidney disease in people with diabetes mellitus. Nat. Rev. Nephrol. 20, 433–446 (2024). 38570632 · DOI · Paper page
  30. [34]Bonner, R., Albajrami, O., Hudspeth, J. & Upadhyay, A. Diabetic kidney disease. Prim. Care 47, 645–659 (2020). 33121634 · DOI
  31. [35]Cortinovis, M., Perico, N., Ruggenenti, P., Remuzzi, A. & Remuzzi, G. Glomerular hyperfiltration. Nat. Rev. Nephrol. 18, 435–451 (2022). 35365815 · DOI · Paper page
  32. [37]Stefansson, V. T. N. et al. Molecular programs associated with glomerular hyperfiltration in early diabetic kidney disease. Kidney Int. 102, 1345–1358 (2022). 36055599 PMC10161735 · DOI
  33. [38]Yao, X. et al. Klotho Ameliorates Podocyte Injury through Targeting TRPC6 Channel in Diabetic Nephropathy. J. Diabetes Res. 2022, 1329380 (2022). 35480629 PMC9038427 · DOI
  34. [39]Qi, C. et al. Increased dishevelled associated activator of morphogenesis 2, a new podocyte-associated protein, in diabetic nephropathy. Nephrol. Dial. Transpl. 36, 1006–1016 (2021). PMC8599908 33544843 · DOI
  35. [40]Akhtar, M., Taha, N. M., Nauman, A., Mujeeb, I. B. & Al-Nabet, A. Diabetic kidney disease: past and present. Adv. Anat. Pathol. 27, 87–97 (2020). 31876542 · DOI
  36. [41]Susztak, K., Raff, A. C., Schiffer, M. & Bottinger, E. P. Glucose-induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy. Diabetes 55, 225–233 (2006). 16380497 · DOI
  37. [42]Ducasa, G. M. et al. ATP-binding cassette A1 deficiency causes cardiolipin-driven mitochondrial dysfunction in podocytes. J. Clin. Invest 129, 3387–3400 (2019). 31329164 PMC6668702 · DOI
  38. [43]Zhang, J. et al. ABCA1 deficiency-mediated glomerular cholesterol accumulation exacerbates glomerular endothelial injury and dysfunction in diabetic kidney disease. Metabolism 139, 155377 (2023). 36521550 · DOI
  39. [44]Mohandes, S. et al. Molecular pathways that drive diabetic kidney disease. J. Clin. Investig. 133, e165654 (2023). PMC9927939 36787250
  40. [45]Wei, Y. et al. To target cellular senescence in diabetic kidney disease: the known and the unknown. Clin. Sci. 138, 991–1007 (2024). PMC11327223 39139135 · DOI
  41. [46]Liang, D. et al. Metformin improves the senescence of renal tubular epithelial cells in a high-glucose state through E2F1. Front Pharm. 13, 926211 (2022). PMC9262145 35814218 · DOI
  42. [47]Eleftheriadis, T. et al. Dapagliflozin prevents high-glucose-induced cellular senescence in renal tubular epithelial cells. Int. J. Mol. Sci. 23, 16107 (2022). PMC9781434 36555751
  43. [48]Nian, S. et al. The inhibitory effects of Dulaglutide on cellular senescence against high glucose in human retinal endothelial cells. Hum. Cell 35, 995–1004 (2022). 35583801 · DOI
  44. [49]Sugita, E., Hayashi, K., Hishikawa, A. & Itoh, H. Epigenetic alterations in podocytes in diabetic nephropathy. Front Pharm. 12, 759299 (2021). PMC8497789 34630127 · DOI
  45. [50]Fu, J., Lee, K., Chuang, P. Y., Liu, Z. & He, J. C. Glomerular endothelial cell injury and cross talk in diabetic kidney disease. Am. J. Physiol. Ren. Physiol. 308, F287–F297 (2015). PMC4329492 25411387 · DOI
  46. [51]Tanabe, K., Wada, J. & Sato, Y. Targeting angiogenesis and lymphangiogenesis in kidney disease. Nat. Rev. Nephrol. 16, 289–303 (2020). 32144398 · DOI
  47. [52]Schwager, S. & Detmar, M. Inflammation and Lymphatic Function. Front Immunol. 10, 308 (2019). 30863410 PMC6399417 · DOI
  48. [53]Sandholm, N. et al. Genome-wide meta-analysis and omics integration identifies novel genes associated with diabetic kidney disease. Diabetologia 65, 1495–1509 (2022). 35763030 PMC9345823 · DOI
  49. [54]Yao, L. et al. Mitochondrial dysfunction in diabetic tubulopathy. Metabolism 131, 155195 (2022). 35358497 · DOI
  50. [55]Kanbay, M. et al. Proximal tubule hypertrophy and hyperfunction: a novel pathophysiological feature in disease states. Clin. Kidney J. 17, sfae195 (2024). 39050867 PMC11267238 · DOI
  51. [56]Juszczak, F., Caron, N., Mathew, A. V. & Decleves, A. E. Critical role for AMPK in metabolic disease-induced chronic kidney disease. Int. J. Mol. Sci. 21, 7994 (2020). 33121167 PMC7663488 · DOI
  52. [57]Hong, Q. et al. Modulation of transforming growth factor-beta-induced kidney fibrosis by leucine-rich α-2 glycoprotein-1. Kidney Int 101, 299–314 (2022). 34774561 PMC8792236 · DOI
  53. [58]Tang, S. C. W. & Yiu, W. H. Innate immunity in diabetic kidney disease. Nat. Rev. Nephrol. 16, 206–222 (2020). 31942046 · DOI
  54. [59]Yang, M. & Zhang, C. The role of innate immunity in diabetic nephropathy and their therapeutic consequences. J. Pharm. Anal. 14, 39–51 (2024). 38352948 PMC10859537 · DOI
  55. [60]Braga, T. T. et al. MyD88 signaling pathway is involved in renal fibrosis by favoring a TH2 immune response and activating alternative M2 macrophages. Mol. Med 18, 1231–1239 (2012). 22777483 PMC3510298 · DOI
  56. [61]Sierra-Mondragon, E. et al. All-trans retinoic acid ameliorates inflammatory response mediated by TLR4/NF-kappaB during initiation of diabetic nephropathy. J. Nutr. Biochem 60, 47–60 (2018). 30193155 · DOI
  57. [62]Zhao, W. et al. Metabolic Dysfunction in the Regulation of the NLRP3 Inflammasome Activation: A Potential Target for Diabetic Nephropathy. J. Diabetes Res 2022, 2193768 (2022). 35719709 PMC9203236 · DOI
  58. [63]Lu, Q. et al. Complement factor B in high glucose-induced podocyte injury and diabetic kidney disease. JCI Insight. 6, e147716 (2021). PMC8525650 34622800
  59. [64]Duan, S. et al. Association of glomerular complement C4c deposition with the progression of diabetic kidney disease in patients with type 2 diabetes. Front. Immunol. 11, 2073 (2020). 32983156 PMC7492595 · DOI
  60. [65]Sircar, M. et al. Complement 7 is up-regulated in human early diabetic kidney disease. Am. J. Pathol. 188, 2147–2154 (2018). 30253844 PMC6180251 · DOI
  61. [66]Trambas, I. A., Coughlan, M. T. & Tan, S. M. Therapeutic potential of targeting complement C5a receptors in diabetic kidney disease. Int. J. Mol. Sci. 24, 8758 (2023). 37240105 PMC10218149 · DOI
  62. [67]Satoskar, A. A. et al. Characterization of glomerular diseases using proteomic analysis of laser capture microdissected glomeruli. Mod. Pathol. 25, 709–721 (2012). 22282304 PMC3432020 · DOI
  63. [68]Li, L. et al. C3a and C5a receptor antagonists ameliorate endothelial-myofibroblast transition via the Wnt/beta-catenin signaling pathway in diabetic kidney disease. Metabolism 64, 597–610 (2015). 25682062 · DOI
  64. [69]Xu, Z., Tao, L. & Su, H. The complement system in metabolic-associated kidney diseases. Front. Immunol. 13, 902063 (2022). 35924242 PMC9339597 · DOI
  65. [70]Flyvbjerg, A. The role of the complement system in diabetic nephropathy. Nat. Rev. Nephrol. 13, 311–318 (2017). 28262777 · DOI
  66. [71]Rayego-Mateos, S. et al. Targeting inflammation to treat diabetic kidney disease: the road to 2030. Kidney Int. 103, 282–296 (2023). 36470394 · DOI
  67. [72]Yang, T. et al. An update on chronic complications of diabetes mellitus: from molecular mechanisms to therapeutic strategies with a focus on metabolic memory. Mol. Med. 30, 71 (2024). 38797859 PMC11128119 · DOI
  68. [73]Kato, M. & Natarajan, R. Epigenetics and epigenomics in diabetic kidney disease and metabolic memory. Nat. Rev. Nephrol. 15, 327–345 (2019). 30894700 PMC6889804 · DOI
  69. [74]Yoshimoto, N. et al. Significance of podocyte DNA damage and glomerular DNA methylation in CKD patients with proteinuria. Hypertens. Res. 46, 1000–1008 (2023). 36646881 · DOI
  70. [75]Gu, X. et al. N6-methyladenosine demethylase FTO promotes M1 and M2 macrophage activation. Cell Signal 69, 109553 (2020). 32018056 · DOI
  71. [77]Kozakova, M., Morizzo, C., Fraser, A. G. & Palombo, C. Impact of glycemic control on aortic stiffness, left ventricular mass and diastolic longitudinal function in type 2 diabetes mellitus. Cardiovasc. Diabetol. 16, 78 (2017). 28623932 PMC5473965 · DOI
  72. [78]Medina-Leyte, D. J. et al. Endothelial dysfunction, inflammation and coronary artery disease: potential biomarkers and promising therapeutical approaches. Int. J. Mol. Sci. 22, 3850 (2021). 33917744 PMC8068178 · DOI
  73. [79]Saenz-Medina, J. et al. Endothelial dysfunction: an intermediate clinical feature between urolithiasis and cardiovascular diseases. Int. J. Mol. Sci. 23, 912 (2022). 35055099 PMC8778796 · DOI
  74. [80]Montanaro, R. et al. Hydrogen sulfide donor AP123 restores endothelial nitric oxide-dependent vascular function in hyperglycemia via a CREB-dependent pathway. Redox Biol. 62, 102657 (2023). 36913800 PMC10025109 · DOI
  75. [81]Zhang, X. et al. Ion channel Piezo1 activation aggravates the endothelial dysfunction under a high glucose environment. Cardiovasc. Diabetol. 23, 150 (2024). 38702777 PMC11067304 · DOI
  76. [82]Yao, Y. et al. Endothelial cell metabolic memory causes cardiovascular dysfunction in diabetes. Cardiovasc. Res. 118, 196–211 (2022). 33483741 · DOI
  77. [83]Huang, Q. et al. Uncovering endothelial to mesenchymal transition drivers in atherosclerosis via multi-omics analysis. BMC Cardiovasc. Disord. 25, 104 (2025). 39956907 PMC11831781 · DOI
  78. [84]Zhao, G. et al. Endothelial KLF11 is a novel protector against diabetic atherosclerosis. Cardiovasc. Diabetol. 23, 381 (2024). 39462409 PMC11514907 · DOI
  79. [85]Liu, L. et al. Bone marrow mesenchymal stem cell-derived extracellular vesicles alleviate diabetes-exacerbated atherosclerosis via AMPK/mTOR pathway-mediated autophagy-related macrophage polarization. Cardiovasc. Diabetol. 24, 48 (2025). 39881287 PMC11780875 · DOI
  80. [86]Bai, X. et al. CAV1-CAVIN1-LC3B-mediated autophagy regulates high glucose-stimulated LDL transcytosis. Autophagy 16, 1111–1129 (2020). 31448673 PMC7469686 · DOI
  81. [87]Zhang, Z. et al. USF1 transcriptionally activates USP14 to drive atherosclerosis by promoting EndMT through NLRC5/Smad2/3 axis. Mol. Med. 30, 32 (2024). 38424494 PMC10905873 · DOI
  82. [88]Cheng, C. K. et al. SOX4 is a novel phenotypic regulator of endothelial cells in atherosclerosis revealed by single-cell analysis. J. Adv. Res 43, 187–203 (2023). 36585108 PMC9811326 · DOI
  83. [89]Supinski, G. S., Schroder, E. A. & Callahan, L. A. Mitochondria and critical illness. Chest 157, 310–322 (2020). 31494084 PMC7005375 · DOI
  84. [90]Zhang, Y. et al. Liraglutide prevents high glucose induced HUVECs dysfunction via inhibition of PINK1/Parkin-dependent mitophagy. Mol. Cell Endocrinol. 545, 111560 (2022). 35032624 · DOI
  85. [91]Heather, L. C., Gopal, K., Srnic, N. & Ussher, J. R. Redefining diabetic cardiomyopathy: perturbations in substrate metabolism at the heart of its pathology. Diabetes 73, 659–670 (2024). 38387045 PMC11043056 · DOI
  86. [92]Zhang, Y., Zhang, Z., Tu, C., Chen, X. & He, R. Advanced glycation end products in disease development and potential interventions. Antioxidants 14, 492 (2025). 40298887 PMC12024296 · DOI
  87. [93]Bansal, S., Burman, A. & Tripathi, A. K. Advanced glycation end products: key mediator and therapeutic target of cardiovascular complications in diabetes. World J. Diabetes 14, 1146–1162 (2023). 37664478 PMC10473940 · DOI
  88. [94]Souders, C. A., Bowers, S. L. & Baudino, T. A. Cardiac fibroblast: the renaissance cell. Circ. Res 105, 1164–1176 (2009). 19959782 PMC3345531 · DOI
  89. [95]Ndumele, C. E. et al. A synopsis of the evidence for the science and clinical management of cardiovascular-kidney-metabolic (CKM) syndrome: a scientific statement from the American Heart Association. Circulation 148, 1636–1664 (2023). 37807920 · DOI · Paper page
  90. [96]Meng, L. et al. METTL14 suppresses pyroptosis and diabetic cardiomyopathy by downregulating TINCR lncRNA. Cell Death Dis. 13, 38 (2022). 35013106 PMC8748685 · DOI
  91. [97]Maisch, B., Alter, P. & Pankuweit, S. Diabetic cardiomyopathy–fact or fiction?. Herz 36, 102–115 (2011). 21424347 · DOI
  92. [98]Falcao-Pires, I. & Leite-Moreira, A. F. Diabetic cardiomyopathy: understanding the molecular and cellular basis to progress in diagnosis and treatment. Heart Fail. Rev. 17, 325–344 (2012). 21626163 · DOI
  93. [99]Sun, Q., Karwi, Q. G., Wong, N. & Lopaschuk, G. D. Advances in myocardial energy metabolism: metabolic remodelling in heart failure and beyond. Cardiovasc. Res. 120, 1996–2016 (2024). 39453987 PMC11646102 · DOI
  94. [100]McDonagh, T. A. et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J. 42, 3599–3726 (2021). 34447992 · DOI · Paper page
  95. [101]Gladden, J. D., Chaanine, A. H. & Redfield, M. M. Heart failure with preserved ejection fraction. Annu. Rev. Med. 69, 65–79 (2018). 29414252 · DOI
  96. [102]Dia, M. et al. Effect of metformin on T2D-induced MAM Ca(2+) uncoupling and contractile dysfunction in an early mouse model of diabetic HFpEF. Int. J. Mol. Sci. 23, 3569 (2022). 35408928 PMC8998623 · DOI
  97. [103]Lazo, M. et al. Soluble receptor for advanced glycation end products and the risk for incident heart failure: the atherosclerosis risk in communities study. Am. Heart J. 170, 961–967 (2015). 26542505 PMC4638130 · DOI
  98. [104]Ren, J., Wu, N. N., Wang, S., Sowers, J. R. & Zhang, Y. Obesity cardiomyopathy: evidence, mechanisms, and therapeutic implications. Physiol. Rev. 101, 1745–1807 (2021). 33949876 PMC8422427 · DOI
  99. [105]Nagayach, A. et al. Advancing the understanding of diabetic encephalopathy through unravelling pathogenesis and exploring future treatment perspectives. Ageing Res. Rev. 100, 102450 (2024). 39134179 · DOI
  100. [106]Nie, S. D. et al. High glucose forces a positive feedback loop connecting ErbB4 expression and mTOR/S6K pathway to aggravate the formation of tau hyperphosphorylation in differentiated SH-SY5Y cells. Neurobiol. Aging 67, 171–180 (2018). 29674181 · DOI
  101. [107]Yang, Y. et al. The imbalance of PGD2-DPs pathway is involved in the type 2 diabetes brain injury by regulating autophagy. Int. J. Biol. Sci. 17, 3993–4004 (2021). 34671214 PMC8495389 · DOI
  102. [108]Taile, J., Arcambal, A., Clerc, P., Gauvin-Bialecki, A. & Gonthier, M. P. Medicinal plant polyphenols attenuate oxidative stress and improve inflammatory and vasoactive markers in cerebral endothelial cells during hyperglycemic condition. Antioxidants 9, 573 (2020). 32630636 PMC7402133 · DOI
  103. [109]Lee, K. S. et al. Hyperglycemia enhances brain susceptibility to lipopolysaccharide-induced neuroinflammation via astrocyte reprogramming. J. Neuroinflamm. 21, 137 (2024). PMC11131277 38802820 · DOI
  104. [110]Ge, X. et al. Electroacupuncture improves cognitive impairment in diabetic cognitive dysfunction rats by regulating the mitochondrial autophagy pathway. J. Physiol. Sci. 72, 29 (2022). 36418941 PMC10717526 · DOI
  105. [111]Zhao, H. et al. Hydrogen sulfide plays an important role by regulating endoplasmic reticulum stress in diabetes-related diseases. Int. J. Mol. Sci. 23, 7170 (2022). 35806174 PMC9266787 · DOI
  106. [112]Sousa, L., Oliveira, M. M., Pessoa, M. T. C. & Barbosa, L. A. Iron overload: effects on cellular biochemistry. Clin. Chim. Acta 504, 180–189 (2020). 31790701 · DOI
  107. [113]Swain, S. K., Chandra Dash, U. & Sahoo, A. K. Hydrolea zeylanica improves cognitive impairment in high-fat diet fed-streptozotocin-induced diabetic encephalopathy in rats via regulating oxidative stress, neuroinflammation, and neurotransmission in brain. Heliyon 8, e11301 (2022). 36387425 PMC9640967 · DOI
  108. [114]Golledge, J. Update on the pathophysiology and medical treatment of peripheral artery disease. Nat. Rev. Cardiol. 19, 456–474 (2022). 34997200 · DOI
  109. [115]Jude, E. B., Oyibo, S. O., Chalmers, N. & Boulton, A. J. Peripheral arterial disease in diabetic and nondiabetic patients: a comparison of severity and outcome. Diabetes Care 24, 1433–1437 (2001). 11473082 · DOI
  110. [116]Mozes, G. et al. Atherosclerosis in amputated legs of patients with and without diabetes mellitus. Int. Angiol. 17, 282–286 (1998). 10204663
  111. [117]Nikolajevic, J. & Sabovic, M. Inflammatory, metabolic, and coagulation effects on medial arterial calcification in patients with peripheral arterial disease. Int. J. Mol. Sci. 24, 3132 (2023). PMC9962230 36834544
  112. [118]Zayed, M. G. et al. Diabetic retinopathy and quality of life: a systematic review and meta-analysis. JAMA Ophthalmol. 142, 199–207 (2024). 38300578 PMC10835609 · DOI · Paper page
  113. [119]Ling, F., Zhang, C., Zhao, X., Xin, X. & Zhao, S. Identification of key genes modules linking diabetic retinopathy and circadian rhythm. Front. Immunol. 14, 1260350 (2023). 38124748 PMC10730663 · DOI
  114. [120]Wong, T. Y., Cheung, C. M., Larsen, M., Sharma, S. & Simo, R. Diabetic retinopathy. Nat. Rev. Dis. Prim. 2, 16012 (2016). 27159554 · DOI
  115. [121]Hassan, J. W. & Bhatwadekar, A. D. Senolytics in the treatment of diabetic retinopathy. Front. Pharm. 13, 896907 (2022). PMC9462063 36091769 · DOI
  116. [122]Han, X. Y. et al. Targeting endothelial glycolytic reprogramming by tsRNA-1599 for ocular anti-angiogenesis therapy. Theranostics 14, 3509–3525 (2024). 38948065 PMC11209708 · DOI
  117. [123]Yu, F. et al. Dynamic O-GlcNAcylation coordinates ferritinophagy and mitophagy to activate ferroptosis. Cell Discov. 8, 40 (2022). 35504898 PMC9065108 · DOI
  118. [124]Zhang, J., Qiu, Q., Wang, H., Chen, C. & Luo, D. TRIM46 contributes to high glucose-induced ferroptosis and cell growth inhibition in human retinal capillary endothelial cells by facilitating GPX4 ubiquitination. Exp. Cell Res. 407, 112800 (2021). 34487731 · DOI
  119. [125]Gu, C. et al. miR-590-3p inhibits pyroptosis in diabetic retinopathy by targeting NLRP1 and inactivating the NOX4 signaling pathway. Investig. Ophthalmol. Vis. Sci. 60, 4215–4223 (2019). 31618425 · DOI
  120. [126]Wang, Q. et al. Poly (ADP-ribose) polymerase 1 mediated arginase II activation is responsible for oxidized LDL-induced endothelial dysfunction. Front Pharm. 9, 882 (2018). PMC6104189 30158868 · DOI
  121. [127]Oshitari, T. Neurovascular cell death and therapeutic strategies for diabetic retinopathy. Int. J. Mol. Sci. 24, 12919 (2023). PMC10454228 37629100
  122. [128]Li, L. et al. Ferroptosis: new insight into the mechanisms of diabetic nephropathy and retinopathy. Front Endocrinol. (Lausanne) 14, 1215292 (2023). 37600716 PMC10435881 · DOI
  123. [129]Wolf, J. et al. Liquid-biopsy proteomics combined with AI identifies cellular drivers of eye aging and disease in vivo. Cell 186, 4868–4884.e4812 (2023). 37863056 PMC10720485 · DOI
  124. [130]Yao, Y. et al. Macrophage/microglia polarization for the treatment of diabetic retinopathy. Front Endocrinology 14, 1276225 (2023). PMC10569308 37842315 · DOI
  125. [131]Lv, K. et al. Integrated multi-omics reveals the activated retinal microglia with intracellular metabolic reprogramming contributes to inflammation in STZ-induced early diabetic retinopathy. Front. Immunol. 13, 942768 (2022). 36119084 PMC9479211 · DOI
  126. [132]Ben, S. et al. Microglia-endothelial cross-talk regulates diabetes-induced retinal vascular dysfunction through remodeling inflammatory microenvironment. iScience 27, 109145 (2024). 38414848 PMC10897849 · DOI
  127. [133]Xu, Y. et al. Single-cell transcriptomes reveal a molecular link between diabetic kidney and retinal lesions. Commun. Biol. 6, 912 (2023). 37670124 PMC10480496 · DOI
  128. [134]He, C. et al. A specific RIP3(+) subpopulation of microglia promotes retinopathy through a hypoxia-triggered necroptotic mechanism. Proc. Natl Acad. Sci. USA 118, e2023290118 (2021). 33836603 PMC7980367 · DOI
  129. [135]Binet, F. et al. Neutrophil extracellular traps target senescent vasculature for tissue remodeling in retinopathy. Science 369, eaay5356 (2020). 32820093 · DOI · Paper page
  130. [136]Zhang, X., Zhang, F. & Xu, X. Single-cell RNA sequencing in exploring the pathogenesis of diabetic retinopathy. Clin. Transl. Med. 14, e1751 (2024). 38946005 PMC11214886 · DOI
  131. [137]Van Hove, I. et al. Single-cell transcriptome analysis of the Akimba mouse retina reveals cell-type-specific insights into the pathobiology of diabetic retinopathy. Diabetologia 63, 2235–2248 (2020). 32734440 · DOI
  132. [138]Zhang, X. et al. Association of plasma osteopontin with diabetic retinopathy in Asians with type 2 diabetes. Mol. Vis. 24, 165–173 (2018). 29463954 PMC5815337
  133. [139]Bai, C. W. et al. G protein subunit alpha i2 pivotal role in angiogenesis. Theranostics 14, 2190–2209 (2024). 38505600 PMC10945342 · DOI
  134. [140]Younossi, Z. M. et al. The global epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis among patients with type 2 diabetes. Clin. Gastroenterol. Hepatol. 22, 1999–2010.e1998 (2024). 38521116 · DOI · Paper page
  135. [141]Chen, Y. et al. Effect of Moderate and vigorous aerobic exercise on incident diabetes in adults with obesity: a 10-year follow-up of a randomized clinical trial. JAMA Intern Med 183, 272–275 (2023). 36716009 PMC9887527 · DOI
  136. [142]Badmus, O. O., Hillhouse, S. A., Anderson, C. D., Hinds, T. D. & Stec, D. E. Molecular mechanisms of metabolic associated fatty liver disease (MAFLD): functional analysis of lipid metabolism pathways. Clin. Sci. 136, 1347–1366 (2022). PMC9508552 36148775 · DOI
  137. [143]Al-Sofiani, M. E., Ganji, S. S. & Kalyani, R. R. Body composition changes in diabetes and aging. J. Diabetes Complic. 33, 451–459 (2019). PMC6690191 31003924 · DOI
  138. [144]Bassi-Dibai, D. et al. Rehabilitation of individuals with diabetes mellitus: focus on diabetic myopathy. Front Endocrinol. 13, 869921 (2022). PMC9047902 35498435 · DOI
  139. [145]Hernandez-Ochoa, E. O. & Vanegas, C. Diabetic myopathy and mechanisms of disease. Biochem. Pharm. 4, e179 (2015). PMC4675628 26693099
  140. [146]Bahn, Y. J. et al. CDK4-E2F3 signals enhance oxidative skeletal muscle fiber numbers and function to affect myogenesis and metabolism. J. Clin. Investig. 133, e162479 (2023). 37395281 PMC10313363 · DOI
  141. [147]Castillo, I. M. P., Argiles, J. M., Rueda, R., Ramirez, M. & Pedrosa, J. M. L. Skeletal muscle atrophy and dysfunction in obesity and type-2 diabetes mellitus: Myocellular mechanisms involved. Rev. Endocr. Metab. Disord. (2025). Online ahead of print. 10.1007/s11154-025-09954-9. PMC12534344 40064750 · DOI
  142. [148]Espino-Gonzalez, E. et al. Impaired skeletal muscle regeneration in diabetes: from cellular and molecular mechanisms to novel treatments. Cell Metab. 36, 1204–1236 (2024). 38490209 · DOI
  143. [149]Rebelos, E., Anastasiou, I. A., Tentolouris, A., Papanas, N. & Jude, E. What is new on diabetic neuropathy? Insights from the 2023 ADA and EASD conferences. Int. J. Low. Extrem Wounds 28, 15347346241233938 (2024). 38414376 · DOI
  144. [150]Hong, T. et al. The prevalence of cardiovascular disease in adults with type 2 diabetes in China: results from the cross-sectional CAPTURE study. Diabetes Ther. 13, 969–981 (2022). 35312971 PMC9076769 · DOI
  145. [151]Gordois, A., Scuffham, P., Shearer, A., Oglesby, A. & Tobian, J. A. The health care costs of diabetic peripheral neuropathy in the US. Diabetes Care 26, 1790–1795 (2003). 12766111 · DOI
  146. [152]Lee, C. G. et al. Prevalence of distal symmetrical polyneuropathy by diabetes prevention program treatment group, diabetes status, duration of diabetes, and cumulative glycemic exposure. Diabetes Care 47, 810–817 (2024). 38502874 PMC11043227 · DOI
  147. [153]Boulton, A. J. M. A brief overview of the diabetic neuropathies. Diabetes Res Clin. Pr. 206, 110758 (2023). 38245328 · DOI
  148. [154]Pop-Busui, R. et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care 40, 136–154 (2017). 27999003 PMC6977405 · DOI · Paper page
  149. [155]Yorek, M. Treatment for diabetic peripheral neuropathy: what have we learned from animal models?. Curr. Diabetes Rev. 18, e040521193121 (2022). 33949936 PMC8965779 · DOI
  150. [156]Eid, S. A. et al. New perspectives in diabetic neuropathy. Neuron 111, 2623–2641 (2023). 37263266 PMC10525009 · DOI
  151. [157]Elafros, M. A. et al. Towards prevention of diabetic peripheral neuropathy: clinical presentation, pathogenesis, and new treatments. Lancet Neurol. 21, 922–936 (2022). 36115364 PMC10112836 · DOI
  152. [158]Wang, L. et al. Exosomes derived from schwann cells ameliorate peripheral neuropathy in type 2 diabetic mice. Diabetes 69, 749–759 (2020). 31915154 PMC7085247 · DOI
  153. [159]Gonzalez-Alvarez, M. E., Sanchez-Romero, E. A., Turroni, S., Fernandez-Carnero, J. & Villafane, J. H. Correlation between the altered gut microbiome and lifestyle interventions in chronic widespread pain patients: a systematic review. Medicines 59, 256 (2023). PMC9964638 36837458 · DOI
  154. [160]Yang, J. et al. Gut microbiota modulate distal symmetric polyneuropathy in patients with diabetes. Cell Metab. 35, 1548–1562.e1547 (2023). 37451270 · DOI
  155. [161]Li, W. et al. Identification of immune infiltration and the potential biomarkers in diabetic peripheral neuropathy through bioinformatics and machine learning methods. Biomolecules 13, 39 (2022). 36671424 PMC9855866 · DOI
  156. [162]Lan, Z., Wei, Y., Yue, K., He, R. & Jiang, Z. Genetically predicted immune cells mediate the association between gut microbiota and neuropathy pain. Inflammopharmacology 32, 3357–3373 (2024). 38955934 PMC11416384 · DOI
  157. [163]Fu, X. L. et al. Global recurrence rates in diabetic foot ulcers: a systematic review and meta-analysis. Diabetes Metab. Res Rev. 35, e3160 (2019). 30916434 · DOI
  158. [164]Deng, H. et al. Mechanisms of diabetic foot ulceration: a review. J. Diabetes 15, 299–312 (2023). 36891783 PMC10101842 · DOI
  159. [165]Soyoye, D. O., Abiodun, O. O., Ikem, R. T., Kolawole, B. A. & Akintomide, A. O. Diabetes and peripheral artery disease: a review. World J. Diabetes 12, 827–838 (2021). 34168731 PMC8192257 · DOI
  160. [166]Edmonds, M., Manu, C. & Vas, P. The current burden of diabetic foot disease. J. Clin. Orthop. Trauma 17, 88–93 (2021). 33680841 PMC7919962 · DOI
  161. [167]Villa, F. et al. Anaerobes in diabetic foot infections: pathophysiology, epidemiology, virulence, and management. Clin. Microbiol. Rev. 37, e0014323 (2024). 38819166 PMC11391693 · DOI
  162. [168]Bashir, H., Multani, H. & Aleem, S. Bacteriological profile and antimicrobial sensitivity pattern of isolates from diabetic foot of patients attending a teaching hospital in Northern India. Asian J. Med. Sci. 12, 83–87 (2021). · DOI
  163. [170]Xourafa, G., Korbmacher, M. & Roden, M. Inter-organ crosstalk during development and progression of type 2 diabetes mellitus. Nat. Rev. Endocrinol. 20, 27–49 (2024). 37845351 · DOI · Paper page
  164. [171]Pereira, S., Cline, D. L., Glavas, M. M., Covey, S. D. & Kieffer, T. J. Tissue-specific effects of leptin on glucose and lipid metabolism. Endocr. Rev. 42, 1–28 (2021). 33150398 PMC7846142 · DOI
  165. [172]Wang, X., Jia, J. & Huang, T. Shared genetic architecture and casual relationship between leptin levels and type 2 diabetes: large-scale cross-trait meta-analysis and Mendelian randomization analysis. BMJ Open Diabetes Res Care 8, e001140 (2020). 32341051 PMC7202746 · DOI
  166. [173]Perry, R. J. & Shulman, G. I. The role of leptin in maintaining plasma glucose during starvation. Postdoc J. 6, 3–19 (2018). 29682594 PMC5909716
  167. [174]Metz, M. et al. Leptin increases hepatic triglyceride export via a vagal mechanism in humans. Cell Metab. 34, 1719–1731.e1715 (2022). 36220067 · DOI
  168. [175]Egbuche, O. et al. Fatty acid binding protein-4 and risk of cardiovascular disease: the cardiovascular health study. J. Am. Heart Assoc. 9, e014070 (2020). 32248728 PMC7428637 · DOI
  169. [176]Kim, M. et al. The impact of endotrophin on the progression of chronic liver disease. Exp. Mol. Med. 52, 1766–1776 (2020). 33110211 PMC8080612 · DOI
  170. [177]An, Y. A. et al. Endotrophin neutralization through targeted antibody treatment protects from renal fibrosis in a podocyte ablation model. Mol. Metab. 69, 101680 (2023). 36696925 PMC9918787 · DOI
  171. [178]Tougaard, N. H. et al. Endotrophin as a marker of complications in a type 2 diabetes cohort. Diabetes Care 45, 2746–2748 (2022). 36094080 · DOI
  172. [180]Cetin, E., Pedersen, B., Porter, L. M., Adler, G. K. & Burak, M. F. Protocol for a randomized placebo-controlled clinical trial using pure palmitoleic acid to ameliorate insulin resistance and lipogenesis in overweight and obese subjects with prediabetes. Front. Endocrinol. 14, 1306528 (2023). PMC10835623 38313838 · DOI
  173. [181]Balakrishnan, R. & Thurmond, D. C. Mechanisms by which skeletal muscle myokines ameliorate insulin resistance. Int. J. Mol. Sci. 23, 4636 (2022). 35563026 PMC9102915 · DOI
  174. [182]Riopel, M. et al. Chronic fractalkine administration improves glucose tolerance and pancreatic endocrine function. J. Clin. Investig. 128, 1458–1470 (2018). 29504946 PMC5873865 · DOI
  175. [183]Eckel, J. Myokines in metabolic homeostasis and diabetes. Diabetologia 62, 1523–1528 (2019). 31263909 · DOI
  176. [184]Lai, W. et al. Irisin ameliorates diabetic kidney disease by restoring autophagy in podocytes. FASEB J. 37, e23175 (2023). 37742293 · DOI
  177. [186]Mansoori, S., Ho, M. Y., Ng, K. K. & Cheng, K. K. Branched-chain amino acid metabolism: Pathophysiological mechanism and therapeutic intervention in metabolic diseases. Obes. Rev. 26, e13856 (2025). 39455059 PMC11711082 · DOI
  178. [187]Barlow, J. P. et al. Beta-aminoisobutyric acid is released by contracting human skeletal muscle and lowers insulin release from INS-1 832/3 cells by mediating mitochondrial energy metabolism. Metab. Open 7, 100053 (2020). PMC7479356 32924003 · DOI
  179. [188]Duan, Y. et al. Interleukin-15 in obesity and metabolic dysfunction: current understanding and future perspectives. Obes. Rev. 18, 1147–1158 (2017). 28752527 · DOI
  180. [190]Pafili, K. et al. Mitochondrial respiration is decreased in visceral but not subcutaneous adipose tissue in obese individuals with fatty liver disease. J. Hepatol. 77, 1504–1514 (2022). 35988689 · DOI · Paper page
  181. [191]Flippo, K. H. & Potthoff, M. J. Metabolic messengers: FGF21. Nat. Metab. 3, 309–317 (2021). 33758421 PMC8620721 · DOI · Paper page
  182. [192]Jin, L. et al. FGF21-Sirtuin 3 axis confers the protective effects of exercise against diabetic cardiomyopathy by governing mitochondrial integrity. Circulation 146, 1537–1557 (2022). 36134579 · DOI
  183. [193]Lin, S. et al. Fibroblast Growth Factor 21 Attenuates diabetes-induced renal fibrosis by negatively regulating Tgf-beta-p53-smad2/3-mediated epithelial-to-mesenchymal transition via activation of AKT. Diabetes Metab. J. 44, 158–172 (2020). 31701691 PMC7043973 · DOI
  184. [194]Salgado, J. V., Goes, M. A. & Salgado Filho, N. FGF21 and chronic kidney disease. Metabolism 118, 154738 (2021). 33617873 · DOI
  185. [196]Wang, D. et al. GDF15 promotes weight loss by enhancing energy expenditure in muscle. Nature 619, 143–150 (2023). 37380764 PMC10322716 · DOI
  186. [197]Aghanoori, M. R. et al. CEBPbeta regulation of endogenous IGF-1 in adult sensory neurons can be mobilized to overcome diabetes-induced deficits in bioenergetics and axonal outgrowth. Cell Mol. Life Sci. 79, 193 (2022). 35298717 PMC8930798 · DOI
  187. [198]Li, X., Wu, T. T., Chen, J. & Qiu, W. Elevated expression levels of serum insulin-like growth factor-1, tumor necrosis factor-alpha and vascular endothelial growth factor 165 might exacerbate type 2 diabetic nephropathy. J. Diabetes Investig. 8, 108–114 (2017). 27218216 PMC5217934 · DOI
  188. [199]Zhang, Y. et al. Insulin-like growth factor 1 knockdown attenuates high glucose-induced podocyte injury by promoting the JAK2/STAT signalling-mediated autophagy. Nephrology 29, 394–404 (2024). 38586891 · DOI
  189. [201]Schulze, P. C. Myocardial lipid accumulation and lipotoxicity in heart failure. J. Lipid Res. 50, 2137–2138 (2009). 19687505 PMC2759818 · DOI
  190. [202]Herman-Edelstein, M., Scherzer, P., Tobar, A., Levi, M. & Gafter, U. Altered renal lipid metabolism and renal lipid accumulation in human diabetic nephropathy. J. Lipid Res. 55, 561–572 (2014). 24371263 PMC3934740 · DOI
  191. [203]Wu, M. et al. Sirt5 improves cardiomyocytes fatty acid metabolism and ameliorates cardiac lipotoxicity in diabetic cardiomyopathy via CPT2 de-succinylation. Redox Biol. 73, 103184 (2024). 38718533 PMC11091707 · DOI
  192. [204]Nawrot, M., Peschard, S., Lestavel, S. & Staels, B. Intestine-liver crosstalk in Type 2 diabetes and non-alcoholic fatty liver disease. Metabolism 123, 154844 (2021). 34343577 · DOI
  193. [205]Nauck, M. A., Quast, D. R., Wefers, J. & Pfeiffer, A. F. H. The evolving story of incretins (GIP and GLP-1) in metabolic and cardiovascular disease: a pathophysiological update. Diabetes Obes. Metab. 23, 5–29 (2021). 34310013 · DOI · Paper page
  194. [207]Rosendo-Silva, D. & Matafome, P. Gut-adipose tissue crosstalk: a bridge to novel therapeutic targets in metabolic syndrome?. Obes. Rev. 22, e13130 (2021). 32815267 · DOI
  195. [208]Letchumanan, G. et al. Gut microbiota composition in prediabetes and newly diagnosed type 2 diabetes: a systematic review of observational studies. Front. Cell Infect. Microbiol 12, 943427 (2022). 36046745 PMC9422273 · DOI
  196. [209]Iatcu, C. O., Steen, A. & Covasa, M. Gut microbiota and complications of type-2 diabetes. Nutrients 14, 166 (2021). 35011044 PMC8747253 · DOI
  197. [210]Di Vincenzo, F., Del Gaudio, A., Petito, V., Lopetuso, L. R. & Scaldaferri, F. Gut microbiota, intestinal permeability, and systemic inflammation: a narrative review. Intern. Emerg. Med. 19, 275–293 (2024). 37505311 PMC10954893 · DOI · Paper page
  198. [211]Liu, W. et al. Elevated plasma trimethylamine-N-oxide levels are associated with diabetic retinopathy. Acta Diabetol. 58, 221–229 (2021). 33064205 PMC7889550 · DOI
  199. [212]Winther, S. A. et al. Utility of plasma concentration of trimethylamine N-oxide in predicting cardiovascular and renal complications in individuals with type 1 diabetes. Diabetes Care 42, 1512–1520 (2019). 31123156 PMC7082641 · DOI
  200. [213]Croyal, M. et al. Plasma trimethylamine N-oxide and risk of cardiovascular events in patients with type 2 diabetes. J. Clin. Endocrinol. Metab. 105, dgaa188 (2020). 32301490 · DOI

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  • HIF inhibition: Current strategies and clinical challenges

    Więch-Walów, A., Bartoszewska, S., Barton, A., Czechowicz, P., Dudzik, J., Wielockx, B., Collawn, J. F., & Bartoszewski, R. (2026) · Redox biology · doi:10.1016/j.redox.2026.104220 · Cited by 3 · see citing works

    “In parallel, pathological HIF activation plays a key role in diabetic complications, including nephropathy, retinopathy, and impaired wound healing, largely by driving aberrant angiogenesis, fibrosis, and vascular dysfunction in hypoxic and inflamed tissues [26,232,247].”

Authors
Zhao, L., Yuan, J., Yang, Q., Ma, J., Yang, F., Zou, Y., Liu, K., & Liu, F.
Affiliations
  • Sichuan University (CN)
  • Southwest Medical University (CN)
Corresponding author
Liu, Fang
ORCID
Venue
Signal Transduction and Targeted Therapy
Publisher
Springer Science and Business Media LLC
Published
2026-01-19
Volume
11
Issue
1
Pages
22-22
ISSN
2059-3635 (ISSN-L)
DOI
10.1038/s41392-025-02401-w
PMC
PMC12812840
OpenAlex
W7124751251
Cited by
80
References
43
Citations by year
2026: 80
FWCI
85.05
Type
journal article
Language
en
Open access
Licence
Locations
  • Signal Transduction and Targeted Therapy (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
  • Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
Keywords
diabetes complications, type 2 diabetes, hyperglycemia, multiple organ failure, organ crosstalk, myokines, cytokines, gut microbiota, exosomes, SGLT2 inhibitors, GLP-1 receptor agonists, mineralocorticoid receptor antagonists, combination therapy, mesenchymal stem cells, traditional Chinese medicine, personalized medicine
MeSH terms
Gastrointestinal Microbiome, Sodium-Glucose Transporter 2 Inhibitors, Diabetes Mellitus, Type 2, Humans, Diabetes Complications

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