Cited by 5,339Advanced Glycation End Products researchDiabetes Management and ResearchChronic Kidney Disease and Diabetes

The DOI matches its Crossref record, with a small difference in title or year; 56 of the 56 references it cites were found in a registry or an index.

The Pathobiology of Diabetic Complications

Brownlee, Michael·2005·Diabetes

DOI 10.2337/diabetes.54.6.1615

Open this paper in CoChat — free account

Abstract

It’s a great honor to join the exceptional club of Banting Award winners, many of whom were my role models and mentors. In addition, giving the Banting Lecture also has a very personal meaning to me, because without Frederick Banting, I would have died from type 1 diabetes when I was 8 years old. However, it was already apparent at the time I was diagnosed that for too many people like me, Banting’s discovery of insulin only allowed them to live just long enough to develop blindness, renal failure, and coronary disease. For example, when I started college, the American Diabetes Association’s Diabetes Textbook had this to say to my parents: “The person with type 1 diabetes can be reassured that it is highly likely that he will live at least into his 30s.” Not surprisingly, my parents did not find this particularly reassuring. At the same time we were reading this in 1967, however, the first basic research discovery about the pathobiology of diabetic complications had just been published in Science the previous year. In my Banting Lecture today, I am thus going to tell you a scientific story that is also profoundly personal. I’ve divided my talk into three parts. The first part is called “pieces of the puzzle,” and in it I describe what was learned about the pathobiology of diabetic complications starting with that 1966 Science paper and continuing through the end of the 1990s. In the second part, I present a unified mechanism that links together all of the seemingly unconnected pieces of the puzzle. Finally, in the third part, I focus on three examples of novel therapeutic approaches for the prevention and treatment of diabetic complications, which are all based on the new paradigm of a unifying mechanism for the pathogenesis of diabetic complications. …

Integrity signals

Registry

Crossref · 10.2337/diabetes.54.6.1615

Cites

56 of 56 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus
(1993) · New England Journal of Medicine · doi:10.1056/nejm199309303291401 · Cited by 24,667
Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33)
(1998) · The Lancet · doi:10.1016/s0140-6736(98)07019-6 · Cited by 20,023
Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage
Nishikawa, T., Edelstein, D., Du, X. L., Yamagishi, S.-I., Matsumura, T., Kaneda, Y., Yorek, M. A., Beebe, D., Oates, P. J., Hammes, H.-P., et al. (2000) · Nature · doi:10.1038/35008121 · Cited by 4,277
Self-citation
Oxidative Stress and Diabetic Vascular Complications
Giugliano, D., Ceriello, A., & Paolisso, G. (1996) · Diabetes Care · doi:10.2337/diacare.19.3.257 · Cited by 1,921
High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria
Korshunov, S. S., Skulachev, V. P., & Starkov, A. A. (1997) · FEBS Letters · doi:10.1016/s0014-5793(97)01159-9 · Cited by 1,727
Cloning and expression of a cell surface receptor for advanced glycosylation end products of proteins.
Neeper, M. P., Schmidt, A. M., Brett, J., Yan, S. D., Wang, F., Pan, Y., Elliston, K. O., Stern, D., & SHAW, A. R. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42138-2 · Cited by 1,545
Protein kinase C activation and the development of diabetic complications.
Koya, D., & King, G. L. (1998) · Diabetes · doi:10.2337/diabetes.47.6.859 · Cited by 1,329
Diseases of the mitochondrial DNA
Wallace, D. C. (1992) · Annual Review of Biochemistry · doi:10.1146/annurev.bi.61.070192.005523 · Cited by 1,319
Hyperglycemia-induced mitochondrial superoxide overproduction activates the hexosamine pathway and induces plasminogen activator inhibitor-1 expression by increasing Sp1 glycosylation
Du, X.-L., Edelstein, D., Rossetti, L., Fantus, I. G., Goldberg, H. J., Ziyadeh, F. N., Wu, J., & Brownlee, M. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.22.12222 · Cited by 1,152
Self-citation
Amelioration of Vascular Dysfunctions in Diabetic Rats by an Oral PKC β Inhibitor
Ishii, H., Jirousek, M. R., Koya, D., Takagi, C., Xia, P., Clermont, A. C., Bursell, S., Kern, T. S., Ballas, L. M., Heath, W. F., et al. (1996) · Science · doi:10.1126/science.272.5262.728 · Cited by 1,103

Show all 56 references

Sorted by citations

Oxidative stress and diabetic complications
Giacco, F., & Brownlee, M. (2010) · Circulation Research · doi:10.1161/circresaha.110.223545 · Cited by 5,461
Self-citation
Oxidative stress, aging, and diseases
Liguori, I., Russo, G., Curcio, F., Bulli, G., Aran, L., Della-Morte, D., Gargiulo, G., Testa, G., Cacciatore, F., Bonaduce, D., et al. (2018) · Clinical Interventions in Aging · doi:10.2147/cia.s158513 · Cited by 3,979
Type 2 diabetes mellitus
DeFronzo, R. A., Ferrannini, E., Groop, L., Henry, R. R., Herman, W. H., Holst, J. J., Hu, F. B., Kahn, C. R., Raz, I., Shulman, G. I., et al. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.19 · Cited by 2,611
Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes
Monnier, L., Mas, E., Ginet, C., Michel, F., Villon, L., Cristol, J.-P., & Colette, C. (2006) · JAMA · doi:10.1001/jama.295.14.1681 · Cited by 2,444
Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables
Ahlqvist, E., Storm, P., Käräjämäki, A., Martinell, M., Dorkhan, M., Carlsson, A., Vikman, P., Prasad, R. B., Aly, D. M., Almgren, P., et al. (2018) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(18)30051-2 · Cited by 2,335
Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms
Petrie, J. R., Guzik, T. J., & Touyz, R. M. (2018) · Canadian Journal of Cardiology · doi:10.1016/j.cjca.2017.12.005 · Cited by 1,787
Reciprocal Relationships Between Insulin Resistance and Endothelial Dysfunction: Molecular and Pathophysiological Mechanisms
Kim, J.-A., Montagnani, M., Koh, K. K., & Quon, M. J. (2006) · Circulation · doi:10.1161/circulationaha.105.563213 · Cited by 1,652
Transient high glucose causes persistent epigenetic changes and altered gene expression during subsequent normoglycemia
El-Osta, A., Brasacchio, D., Yao, D., Pocai, A., Jones, P. L., Roeder, R. G., Cooper, M. E., & Brownlee, M. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20081188 · Cited by 1,115
Self-citation
Role of Mitochondrial Dysfunction in Insulin Resistance
Kim, J.-A., Wei, Y., & Sowers, J. R. (2008) · Circulation Research · doi:10.1161/circresaha.107.165472 · Cited by 1,103
Mitochondrial generation of superoxide and hydrogen peroxide as the source of mitochondrial redox signaling
Brand, M. D. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.04.001 · Cited by 1,063
Oxidative stress in obesity: A critical component in human diseases
Marseglia, L., Manti, S., D’Angelo, G., Nicotera, A., Parisi, E., Di Rosa, G., Gitto, E., & Arrigo, T. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms16010378 · Cited by 933
Cross talk between mitochondria and NADPH oxidases
Dikalov, S. (2011) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2011.06.033 · Cited by 783
Diastolic Stiffness of the Failing Diabetic Heart: Importance of Fibrosis, Advanced Glycation End Products, and Myocyte Resting Tension
van Heerebeek, L., Hamdani, N., Handoko, M. L., Falcao-Pires, I., Musters, R. J., Kupreishvili, K., Ijsselmuiden, A. J. J., Schalkwijk, C. G., Bronzwaer, J. G. F., Diamant, M., et al. (2008) · Circulation · doi:10.1161/circulationaha.107.728550 · Cited by 723
Diabetes associated cell stress and dysfunction: role of mitochondrial and non-mitochondrial ROS production and activity.
Newsholme, P., Haber, E. P., Hirabara, S. M., Rebelato, E. L. O., Procopio, J., Morgan, D., Oliveira‐Emilio, H. C., Carpinelli, A. R., & Curi, R. (2007) · The Journal of Physiology · doi:10.1113/jphysiol.2007.135871 · Cited by 684
Diabetes and Kidney Disease: Role of Oxidative Stress
Jha, J. C., Banal, C., Chow, B. S. M., Cooper, M. E., & Jandeleit-Dahm, K. (2016) · Antioxidants & Redox Signaling · doi:10.1089/ars.2016.6664 · Cited by 660
The Role of Advanced Glycation End Products in Aging and Metabolic Diseases: Bridging Association and Causality
Chaudhuri, J., Bains, Y., Guha, S., Kahn, A., Hall, D., Bose, N., Gugliucci, A., & Kapahi, P. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.08.014 · Cited by 669
“…anuscript A uthor M anuscript A uthor M anuscript A uthor M anuscript Diabetic macroangiopathy The detoxification of α-DCs, a precursor of AGE, also underlies the prevention of diabetesmediated micro and macro vascular damage that may contribute to atherosclerosis and stroke (Brownlee, 2001, 2005).”
Background
Reactive oxygen species (ROS) in macrophage activation and function in diabetes
Rendra, E., Riabov, V., Mossel, D. M., Sevastyanova, T., Harmsen, M. C., & Kzhyshkowska, J. (2019) · Immunobiology · doi:10.1016/j.imbio.2018.11.010 · Cited by 636
Insulin Resistance and Atherosclerosis: Implications for Insulin-Sensitizing Agents
Di Pino, A., & DeFronzo, R. A. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00141 · Cited by 535
Patients with type 2 diabetes have normal mitochondrial function in skeletal muscle
Boushel, R., Gnaiger, E., Schjerling, P., Skovbro, M., Kraunsøe, R., & Dela, F. (2007) · Diabetologia · doi:10.1007/s00125-007-0594-3 · Cited by 519
Glycemic Variability: A Hemoglobin A1c–Independent Risk Factor for Diabetic Complications
Brownlee, M., & Hirsch, I. B. (2006) · JAMA · doi:10.1001/jama.295.14.1707 · Cited by 482
Self-citation
Advanced Glycation End Products (AGEs): Biochemistry, Signaling, Analytical Methods, and Epigenetic Effects
Perrone, A., Giovino, A., Benny, J., & Martinelli, F. (2020) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2020/3818196 · Cited by 459
The hallmarks of mitochondrial dysfunction in chronic kidney disease
Galvan, D. L., Green, N. H., & Danesh, F. R. (2017) · Kidney International · doi:10.1016/j.kint.2017.05.034 · Cited by 447
Metabolic and nutritional support of critically ill patients: consensus and controversies
Preiser, J.-C., van Zanten, A. R., Berger, M. M., Biolo, G., Casaer, M. P., Doig, G. S., Griffiths, R. D., Heyland, D. K., Hiesmayr, M., Iapichino, G., et al. (2015) · Critical Care · doi:10.1186/s13054-015-0737-8 · Cited by 416
Glucose Variability; Does It Matter?
Siegelaar, S. E., Holleman, F., Hoekstra, J. B. L., & DeVries, J. H. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0021 · Cited by 409
Elevated risk of type 2 diabetes for development of Alzheimer disease: A key role for oxidative stress in brain
Butterfield, D. A., Di Domenico, F., & Barone, E. (2014) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2014.06.010 · Cited by 402
Diabetes and the Risk of Multi-System Aging Phenotypes: A Systematic Review and Meta-Analysis
Lu, F.-P., Lin, K.-P., & Kuo, H.-K. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004144 · Cited by 398
Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus
Tahrani, A. A., Barnett, A. H., & Bailey, C. J. (2016) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2016.86 · Cited by 398
Endothelial Mitochondria: Contributing to Vascular Function and Disease
Davidson, S. M., & Duchen, M. R. (2007) · Circulation Research · doi:10.1161/01.res.0000261970.18328.1d · Cited by 381
Glycemic control and complications in type 2 diabetes mellitus
Stolar, M. (2010) · The American Journal of Medicine · doi:10.1016/j.amjmed.2009.12.004 · Cited by 356
Angiotensin II-Induced Production of Mitochondrial Reactive Oxygen Species: Potential Mechanisms and Relevance for Cardiovascular Disease
Dikalov, S. I., & Nazarewicz, R. R. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.4604 · Cited by 356
JNK1 and IKKβ: molecular links between obesity and metabolic dysfunction
Solinas, G., & Karin, M. (2010) · The FASEB Journal · doi:10.1096/fj.09-151340 · Cited by 347
Nicotinamide Improves Aspects of Healthspan, but Not Lifespan, in Mice
Mitchell, S. J., Bernier, M., Aon, M. A., Cortassa, S., Kim, E. Y., Fang, E. F., Palacios, H. H., Ali, A., Navas-Enamorado, I., Di Francesco, A., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.001 · Cited by 338
The protective roles of GLP-1R signaling in diabetic nephropathy: possible mechanism and therapeutic potential
Fujita, H., Morii, T., Fujishima, H., Sato, T., Shimizu, T., Hosoba, M., Tsukiyama, K., Narita, T., Takahashi, T., Drucker, D. J., et al. (2014) · Kidney International · doi:10.1038/ki.2013.427 · Cited by 336
Oxidative Damage in the Retinal Mitochondria of Diabetic Mice: Possible Protection by Superoxide Dismutase
Kanwar, M., Chan, P.-S., Kern, T. S., & Kowluru, R. A. (2007) · Investigative Opthalmology & Visual Science · doi:10.1167/iovs.06-1280 · Cited by 333
The Pathophysiology of Cardiovascular Disease and Diabetes: Beyond Blood Pressure and Lipids
Dokken, B. B. (2008) · Diabetes Spectrum · doi:10.2337/diaspect.21.3.160 · Cited by 299
Insulin resistance and insulin hypersecretion in the metabolic syndrome and type 2 diabetes: Time for a conceptual framework shift
Nolan, C. J., & Prentki, M. (2019) · Diabetes and Vascular Disease Research · doi:10.1177/1479164119827611 · Cited by 292
The role of glucose transporters in brain disease: Diabetes and Alzheimer’s disease
Shah, K., DeSilva, S., & Abbruscato, T. (2012) · International Journal of Molecular Sciences · doi:10.3390/ijms131012629 · Cited by 288
Oxidative stress and metabolic pathologies: from an adipocentric point of view
Le Lay, S., Simard, G., Martinez, M. C., & Andriantsitohaina, R. (2014) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2014/908539 · Cited by 291
Sirtuin 1-Mediated Cellular Metabolic Memory of High Glucose via the LKB1/AMPK/ROS Pathway and Therapeutic Effects of Metformin
Zheng, Z., Chen, H., Li, J., Li, T., Zheng, B., Zheng, Y., Jin, H., He, Y., Gu, Q., & Xu, X. (2012) · Diabetes · doi:10.2337/db11-0416 · Cited by 282
Autophagy in diabetic kidney disease: regulation, pathological role and therapeutic potential
Yang, D., Livingston, M. J., Liu, Z., Dong, G., Zhang, M., Chen, J.-K., & Dong, Z. (2018) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-017-2639-1 · Cited by 252
Diabetes and Cardiovascular Disease in Older Adults: Current Status and Future Directions
Halter, J. B., Musi, N., McFarland Horne, F., Crandall, J. P., Goldberg, A., Harkless, L., Hazzard, W. R., Huang, E. S., Kirkman, M. S., Plutzky, J., et al. (2014) · Diabetes · doi:10.2337/db14-0020 · Cited by 255
Depression and type 2 diabetes: Inflammatory mechanisms of a psychoneuroendocrine co-morbidity
Stuart, M. J., & Baune, B. T. (2012) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2011.10.001 · Cited by 257
Kidney disease and related findings in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study
de Boer, I. H., & for the DCCT/EDIC Research Group (2014) · Diabetes Care · doi:10.2337/dc13-2113 · Cited by 254
Cardiometabolic-Based Chronic Disease, Adiposity and Dysglycemia Drivers
Mechanick, J. I., Farkouh, M. E., Newman, J. D., & Garvey, W. T. (2020) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2019.11.044 · Cited by 243
Overexpression of mitochondrial superoxide dismutase in mice protects the retina from diabetes-induced oxidative stress
Kowluru, R. A., Kowluru, V., Xiong, Y., & Ho, Y.-S. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2006.01.012 · Cited by 233
Almonds Decrease Postprandial Glycemia, Insulinemia, and Oxidative Damage in Healthy Individuals
Jenkins, D. J. A., Kendall, C. W. C., Josse, A. R., Salvatore, S., Brighenti, F., Augustin, L. S. A., Ellis, P. R., Vidgen, E., & Rao, A. V. (2006) · The Journal of Nutrition · doi:10.1093/jn/136.12.2987 · Cited by 226
Formation of Fructose-Mediated Advanced Glycation End Products and Their Roles in Metabolic and Inflammatory Diseases
Gugliucci, A. (2017) · Advances in Nutrition · doi:10.3945/an.116.013912 · Cited by 225
The Hemoglobin A1c Level as a Progressive Risk Factor for Cardiovascular Death, Hospitalization for Heart Failure, or Death in Patients With Chronic Heart Failure: An Analysis of the Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM) Program
Gerstein, H. C. (2008) · Archives of Internal Medicine · doi:10.1001/archinte.168.15.1699 · Cited by 217
Retinopathy predicts cardiovascular mortality in type 2 diabetic men and women
Juutilainen, A., Lehto, S., Rönnemaa, T., Pyörälä, K., & Laakso, M. (2007) · Diabetes Care · doi:10.2337/dc06-1747 · Cited by 209
Quantifying the Contribution of the Liver to Glucose Homeostasis: A Detailed Kinetic Model of Human Hepatic Glucose Metabolism
König, M., Bulik, S., & Holzhütter, H.-G. (2012) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1002577 · Cited by 202
‘Exercise snacks’ before meals: a novel strategy to improve glycaemic control in individuals with insulin resistance
Francois, M. E., Baldi, J. C., Manning, P. J., Lucas, S. J. E., Hawley, J. A., Williams, M. J. A., & Cotter, J. D. (2014) · Diabetologia · doi:10.1007/s00125-014-3244-6 · Cited by 204
The Role of Dietary Advanced Glycation End Products in Metabolic Dysfunction
Sergi, D., Boulestin, H., Campbell, F. M., & Williams, L. M. (2021) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201900934 · Cited by 194
Diabetes mellitus and stroke: A clinical update
Tun, N. N., Arunagirinathan, G., Munshi, S. K., & Pappachan, J. M. (2017) · World Journal of Diabetes · doi:10.4239/wjd.v8.i6.235 · Cited by 177
Advanced glycation endproducts and its receptor for advanced glycation endproducts in obesity
Gaens, K. H., Stehouwer, C. D., & Schalkwijk, C. G. (2013) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e32835aea13 · Cited by 166
Role of nitrosative stress in the pathogenesis of diabetic vascular dysfunction
Szabo, C. (2009) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2008.00086.x · Cited by 165
The relationship between glycemic variability and diabetic peripheral neuropathy in type 2 diabetes with well-controlled HbA1c
Xu, F., Zhao, L.-H., Su, J.-B., Chen, T., Wang, X.-Q., Chen, J.-F., Wu, G., Jin, Y., & Wang, X.-H. (2014) · Diabetology & Metabolic Syndrome · doi:10.1186/1758-5996-6-139 · Cited by 159
Mitochondrial biogenesis and fission in axons in cell culture and animal models of diabetic neuropathy
Vincent, A. M., Edwards, J. L., McLean, L. L., Hong, Y., Cerri, F., Lopez, I., Quattrini, A., & Feldman, E. L. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0697-7 · Cited by 152
Prolonged fasting identifies skeletal muscle mitochondrial dysfunction as consequence rather than cause of human insulin resistance
Hoeks, J., van Herpen, N. A., Mensink, M., Moonen-Kornips, E., van Beurden, D., Hesselink, M. K. C., & Schrauwen, P. (2010) · Diabetes · doi:10.2337/db10-0519 · Cited by 156
Deep transfer learning and data augmentation improve glucose levels prediction in type 2 diabetes patients
Deng, Y., Lu, L., Aponte, L., Angelidi, A. M., Novak, V., Karniadakis, G. E., & Mantzoros, C. S. (2021) · npj Digital Medicine · doi:10.1038/s41746-021-00480-x · Cited by 152
The Role of Mitochondria in the Pathophysiology of Skeletal Muscle Insulin Resistance
Pagel-Langenickel, I., Bao, J., Pang, L., & Sack, M. N. (2010) · Endocrine Reviews · doi:10.1210/er.2009-0003 · Cited by 154
Acute hyperglycemia and oxidative stress: Direct cause and effect?
Choi, S.-W., Benzie, I. F. F., Ma, S.-W., Strain, J. J., & Hannigan, B. M. (2008) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.12.005 · Cited by 149
Regulation of hepatic glucose production and the role of gluconeogenesis in humans: is the rate of gluconeogenesis constant?
Nuttall, F. Q., Ngo, A., & Gannon, M. C. (2008) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.863 · Cited by 146
Advanced Glycation End Products, Oxidation Products, and Incident Cardiovascular Events in Patients With Type 2 Diabetes
Koska, J., Saremi, A., Howell, S., Bahn, G., De Courten, B., Ginsberg, H., Beisswenger, P. J., Reaven, P. D., & for the VADT Investigators (2018) · Diabetes Care · doi:10.2337/dc17-1740 · Cited by 134
Endothelial Function and Dysfunction: Impact of Metformin
Nafisa, A., Gray, S. G., Cao, Y., Wang, T., Xu, S., Wattoo, F. H., Barras, M., Cohen, N., Kamato, D., & Little, P. J. (2018) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2018.07.007 · Cited by 128
Proteome analysis reveals antiangiogenic environments in chronic wounds of diabetes mellitus type 2 patients
Krisp, C., Jacobsen, F., McKay, M. J., Molloy, M. P., Steinstraesser, L., & Wolters, D. A. (2013) · PROTEOMICS · doi:10.1002/pmic.201200502 · Cited by 124
α-Lipoic Acid Prevents the Increase in Atherosclerosis Induced by Diabetes in Apolipoprotein E–Deficient Mice Fed High-Fat/Low-Cholesterol Diet
Yi, X., & Maeda, N. (2006) · Diabetes · doi:10.2337/db06-0251 · Cited by 117
Comparative effects of microvascular and macrovascular disease on the risk of major outcomes in patients with type 2 diabetes
Mohammedi, K., Woodward, M., Marre, M., Colagiuri, S., Cooper, M., Harrap, S., Mancia, G., Poulter, N., Williams, B., Zoungas, S., et al. (2017) · Cardiovascular Diabetology · doi:10.1186/s12933-017-0574-y · Cited by 111
Succination of Proteins by Fumarate: Mechanism of Inactivation of Glyceraldehyde‐3‐Phosphate Dehydrogenase in Diabetes
Blatnik, M., Thorpe, S. R., & Baynes, J. W. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1433.047 · Cited by 109
Myocardial infarction and heart failure in the db/db diabetic mouse
Greer, J. J. M., Ware, D. P., & Lefer, D. J. (2006) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00583.2005 · Cited by 108
Vascular complications in diabetes: Old messages, new thoughts
Forbes, J. M., & Fotheringham, A. K. (2017) · Diabetologia · doi:10.1007/s00125-017-4360-x · Cited by 106
A Synopsis of the Associations of Oxidative Stress, ROS, and Antioxidants with Diabetes Mellitus
Black, H. S. (2022) · Antioxidants · doi:10.3390/antiox11102003 · Cited by 103
Resveratrol Protects Vascular Endothelial Cells from High Glucose–Induced Apoptosis through Inhibition of NADPH Oxidase Activation–Driven Oxidative Stress
Chen, F., Qian, L., Deng, B., Liu, Z., Zhao, Y., & Le, Y. (2013) · CNS Neuroscience & Therapeutics · doi:10.1111/cns.12131 · Cited by 101
PPARα: an emerging therapeutic target in diabetic microvascular damage
Hiukka, A., Maranghi, M., Matikainen, N., & Taskinen, M.-R. (2010) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2010.89 · Cited by 103
Seminal, ultrasound and psychobiological parameters correlate with metabolic syndrome in male members of infertile couples
Lotti, F., Corona, G., Degli Innocenti, S., Filimberti, E., Scognamiglio, V., Vignozzi, L., Forti, G., & Maggi, M. (2013) · Andrology · doi:10.1111/j.2047-2927.2012.00031.x · Cited by 96
Dietary Patterns and Cardiovascular Disease Risk in People with Type 2 Diabetes
Archundia Herrera, M. C., Subhan, F. B., & Chan, C. B. (2017) · Current Obesity Reports · doi:10.1007/s13679-017-0284-5 · Cited by 98
Advanced Glycation End Products (AGEs), but not High Glucose, Inhibit the Osteoblastic Differentiation of Mouse Stromal ST2 Cells Through the Suppression of Osterix Expression, and Inhibit Cell Growth and Increasing Cell Apoptosis
Okazaki, K., Yamaguchi, T., Tanaka, K.-I., Notsu, M., Ogawa, N., Yano, S., & Sugimoto, T. (2012) · Calcified Tissue International · doi:10.1007/s00223-012-9641-2 · Cited by 98
Myeloid cell dysfunction and the pathogenesis of the diabetic chronic wound
Wicks, K., Torbica, T., & Mace, K. A. (2014) · Seminars in Immunology · doi:10.1016/j.smim.2014.04.006 · Cited by 93
Empagliflozin Ameliorates Type 2 Diabetes-Induced Ultrastructural Remodeling of the Neurovascular Unit and Neuroglia in the Female db/db Mouse
Hayden, M., Grant, D., Aroor, A., & DeMarco, V. (2019) · Brain Sciences · doi:10.3390/brainsci9030057 · Cited by 93
Integrating glycaemic variability in the glycaemic disorders of type 2 diabetes: A move towards a unified glucose tetrad concept
Monnier, L., Colette, C., & Owens, D. R. (2009) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.962 · Cited by 89
Elevation of brain glucose and polyol-pathway intermediates with accompanying brain-copper deficiency in patients with Alzheimer’s disease: Metabolic basis for dementia
Xu, J., Begley, P., Church, S. J., Patassini, S., McHarg, S., Kureishy, N., Hollywood, K. A., Waldvogel, H. J., Liu, H., Zhang, S., et al. (2016) · Scientific Reports · doi:10.1038/srep27524 · Cited by 85
Antioxidant Phytochemicals as Potential Therapy for Diabetic Complications
Akpoveso, O.-O. P., Ubah, E. E., & Obasanmi, G. (2023) · Antioxidants · doi:10.3390/antiox12010123 · Cited by 90
Distribution of Phenolic Contents, Antidiabetic Potentials, Antihypertensive Properties, and Antioxidative Effects of Soursop (Annona muricata L.) Fruit Parts In Vitro
Adefegha, S. A., Oyeleye, S. I., & Oboh, G. (2015) · Biochemistry Research International · doi:10.1155/2015/347673 · Cited by 86
Insulin Resistance in Type 1 Diabetes: Pathophysiological, Clinical, and Therapeutic Relevance
Apostolopoulou, M., Lambadiari, V., Roden, M., & Dimitriadis, G. D. (2025) · Endocrine Reviews · doi:10.1210/endrev/bnae032 · Cited by 90
Acute hyperglycemia induces a global downregulation of gene expression in adipose tissue and skeletal muscle of healthy subjects.
Meugnier, E., Faraj, M., Rome, S., Beauregard, G., Michaut, A., Pelloux, V., Chiasson, J.-L., Laville, M., Clement, K., Vidal, H., et al. (2007) · Diabetes · doi:10.2337/db06-1242 · Cited by 76
Glycated hemoglobin and outcomes in patients with advanced diabetic chronic kidney disease
Kuo, I.-C., Lin, H. Y.-H., Niu, S.-W., Hwang, D.-Y., Lee, J.-J., Tsai, J.-C., Hung, C.-C., Hwang, S.-J., & Chen, H.-C. (2016) · Scientific Reports · doi:10.1038/srep20028 · Cited by 70
Effect of hyperglycemia on mitochondrial respiration in type 2 diabetes.
Rabøl, R., Højberg, P. M. V., Almdal, T., Boushel, R., Haugaard, S. B., Madsbad, S., & Dela, F. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1475 · Cited by 66
Canagliflozin Inhibits Human Endothelial Cell Proliferation and Tube Formation
Behnammanesh, G., Durante, Z. E., Peyton, K. J., Martinez-Lemus, L. A., Brown, S. M., Bender, S. B., & Durante, W. (2019) · Frontiers in Pharmacology · doi:10.3389/fphar.2019.00362 · Cited by 61
Ablation of the gene encoding p66Shc protects mice against AGE-induced glomerulopathy by preventing oxidant-dependent tissue injury and further AGE accumulation
Menini, S., Iacobini, C., Ricci, C., Oddi, G., Pesce, C., Pugliese, F., Block, K., Abboud, H. E., Giorgio, M., Migliaccio, E., et al. (2007) · Diabetologia · doi:10.1007/s00125-007-0728-7 · Cited by 64
The metabolic syndrome and endothelial dysfunction: Common highway to type 2 diabetes and CVD?
Diamant, M., & Tushuizen, M. E. (2006) · Current Diabetes Reports · doi:10.1007/s11892-006-0061-4 · Cited by 64
Acute Effects of Dietary Glycemic Index on Antioxidant Capacity in a Nutrient‐controlled Feeding Study
Botero, D., Ebbeling, C. B., Blumberg, J. B., Ribaya‐Mercado, J. D., Creager, M. A., Swain, J. F., Feldman, H. A., & Ludwig, D. S. (2009) · Obesity · doi:10.1038/oby.2009.203 · Cited by 60
“Hyperglycemia causes overproduction of superoxide anions by the mitochondrial electron transport chain that, in turn, generates reactive oxygen species by numerous metabolic pathways (8).”
Background
Exploring residual risk for diabetes and microvascular disease in the Diabetes Prevention Program Outcomes Study (DPPOS)
Perreault, L., Pan, Q., Aroda, V. R., Barrett-Connor, E., Dabelea, D., Dagogo-Jack, S., Hamman, R. F., Kahn, S. E., Mather, K. J., Knowler, W. C., et al. (2017) · Diabetic Medicine · doi:10.1111/dme.13453 · Cited by 55
Exenatide once weekly for the treatment of type 2 diabetes
Malone, J., Trautmann, M., Wilhelm, K., Taylor, K., & Kendall, D. M. (2009) · Expert Opinion on Investigational Drugs · doi:10.1517/13543780902766802 · Cited by 55
Etiology of type 2 diabetes and Alzheimer’s disease: Exploring the mitochondria
Silzer, T. K., & Phillips, N. R. (2018) · Mitochondrion · doi:10.1016/j.mito.2018.04.004 · Cited by 53
Exenatide improves ovarian and endometrial injury and preserves ovarian reserve in streptozocin induced diabetic rats
Artunc-Ulkumen, B., Pala, H. G., Pala, E. E., Yavasoglu, A., Yigitturk, G., & Erbas, O. (2015) · Gynecological Endocrinology · doi:10.3109/09513590.2014.975686 · Cited by 45
Protective Effects and Molecular Signaling of n-3 Fatty Acids on Oxidative Stress and Inflammation in Retinal Diseases
Suzumura, A., Terao, R., & Kaneko, H. (2020) · Antioxidants · doi:10.3390/antiox9100920 · Cited by 44
Significance of Glycemic Variability in Diabetes Mellitus
Kusunoki, Y., Konishi, K., Tsunoda, T., & Koyama, H. (2022) · Internal Medicine · doi:10.2169/internalmedicine.8424-21 · Cited by 40
Accelerated Aging during Chronic Oxidative Stress: A Role for PARP-1
Boesten, D. M. P. H. J., de Vos-Houben, J. M. J., Timmermans, L., den Hartog, G. J. M., Bast, A., & Hageman, G. J. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/680414 · Cited by 37
How tightly controlled do fluctuations in blood glucose levels need to be to reduce the risk of developing complications in people with type 1 diabetes?
Livingstone, R., Boyle, J. G., & Petrie, J. R. (2020) · Diabetic Medicine · doi:10.1111/dme.13911 · Cited by 34
Double-Edged Action of SOD Mimetic in Diabetic Nephropathy
Asaba, K., Tojo, A., Onozato, M. L., Goto, A., & Fujita, T. (2007) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e31802b6530 · Cited by 35
Tirzepatide alleviates oxidative stress and inflammation in diabetic nephropathy via IL-17 signaling pathway
Yang, Y., Wang, Y., Zhou, Y., Deng, J., & Wu, L. (2025) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-024-05066-1 · Cited by 35

Authors: Brownlee, M.
Affiliations: Albert Einstein College of Medicine (US)
Corresponding author: Brownlee, Michael
Venue: Diabetes
Publisher: American Diabetes Association
Published: 2005-06-01
Volume: 54
Issue: 6
Pages: 1615-1625
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diabetes.54.6.1615
OpenAlex: W2471605942
Cited by: 5,339
References: 56
Citations by year: 2026: 286 · 2025: 248 · 2024: 230 · 2023: 233 · 2022: 299 · 2021: 310 · 2020: 309 · 2019: 295 · 2018: 279 · 2017: 278 · 2016: 281 · 2015: 305 · 2014: 349 · 2013: 294 · 2012: 275
FWCI: 90.14
Type: journal article
Language: en
Open access: closed
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
Keywords: diabetes complications, pathobiology, type 1 diabetes, diabetic nephropathy, diabetic retinopathy, diabetic cardiovascular disease, insulin
MeSH terms: Animals, Humans, Hyperglycemia, Mitochondria, Diabetes Complications

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

The Pathobiology of Diabetic Complications

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks