Cited by 490Retinal Diseases and TreatmentsDiabetes Management and ResearchAdvanced Glycation End Products research

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Progression of Incipient Diabetic Retinopathy During Good Glycemic Control

Engerman, Ronald L, Kern, Timothy S·1987·Diabetes

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Abstract

To assess the extent to which the progression of diabetic retinopathy can be arrested by improved glycemic control, 35 normal dogs were randomly divided into a nondiabetic and three alloxan-induced diabetic groups prospectively identified according to glycemic control: poor control for 5 yr (PC), good control for 5 yr (GC), and poor control for 2.5 yr followed by good control for 2.5 yr (PGC). To achieve good control, insulin was given twice daily together with a measured diet so that hyperglycemia and glucosuria were mild and infrequent, and HbA1 was comparable to normal. Retinal capillary aneurysms and other lesions developed during 60 mo of poor control (group PC) and were inhibited if good control was begun promptly within 2 mo (group GC). In group PGC, retinopathy was absent or equivocal at 2.5 yr of poor control and, surprisingly, was found to develop subsequently despite good glycemic control. Retinopathy in group PGC was greater at autopsy than at 2.5 yr and was greater than in group GC. The results indicate that retinopathy may be preventable but tends to resist arrest even in its incipient stages, before more than the first few aneurysms have appeared.

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Crossref · 10.2337/diab.36.7.808

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Fletcher, E. L., Phipps, J. A., & Wilkinson‐Berka, J. L. (2005) · Clinical and Experimental Optometry · doi:10.1111/j.1444-0938.2005.tb06686.x · Cited by 98
Role of Mitochondria Biogenesis in the Metabolic Memory Associated with the Continued Progression of Diabetic Retinopathy and Its Regulation by Lipoic Acid
dos Santos, J. M., & Kowluru, R. A. (2011) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.11-8203 · Cited by 97
Global DNA methylation as a possible biomarker for diabetic retinopathy
Maghbooli, Z., Hossein‐Nezhad, A., Larijani, B. A., Amini, M., & Keshtkar, A. (2014) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2584 · Cited by 97
“Epidemiological studies and clinical trials have demonstrated that retinopathy occurs in most diabetic patients despite subsequent interventions or metabolic successes [7,8,11,16,19,20].”
Background
Identification of multiple genes in bovine retinal pericytes altered by exposure to elevated levels of glucose by using mRNA differential display.
Aiello, L. P., Robinson, G. S., Lin, Y. W., Nishio, Y., & King, G. L. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.13.6231 · Cited by 96
Endothelial cell metabolic memory causes cardiovascular dysfunction in diabetes
Yao, Y., Song, Q., Hu, C., Da, X., Yu, Y., He, Z., Xu, C., Chen, Q., & Wang, Q. K. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab013 · Cited by 97
Metabolic memory: Mechanisms and implications for diabetic retinopathy
Zhang, L., Chen, B., & Tang, L. (2011) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2011.12.006 · Cited by 97
“The first suggestion of such memory in DR came from a study by Engerman and Kern in the 1980s [8].”
Background
Glucose toxicity in the vascular complications of diabetes: The cellular perspective
Lorenzi, M. (1992) · Diabetes/Metabolism Reviews · doi:10.1002/dmr.5610080202 · Cited by 92
The Effect of Diet and Lifestyle on the Course of Diabetic Retinopathy—A Review of the Literature
Bryl, A., Mrugacz, M., Falkowski, M., & Zorena, K. (2022) · Nutrients · doi:10.3390/nu14061252 · Cited by 98
“Within 5 years, these dogs developed severe diabetic retinopathy, similar to that observed in dogs with poor glycemic control throughout that period [17].”
Background
Proliferative Diabetic Retinopathy
Shah, K. B., & Han, D. P. (2004) · International Ophthalmology Clinics · doi:10.1097/00004397-200404440-00007 · Cited by 94
Comparison of retinal lesions in alloxan-diabetic rats and galactose-fed rats
Kern, T. S., & Engerman, R. L. (1994) · Current Eye Research · doi:10.3109/02713689409015087 · Cited by 93
Self-citation
Specific retinal diacylglycerol and protein kinase C beta isoform modulation mimics abnormal retinal hemodynamics in diabetic rats.
Bursell, S. E., Takagi, C., Clermont, A., et al. (1997) · PubMed · Cited by 92
Resistance of retinal inflammatory mediators to suppress after reinstitution of good glycemic control: novel mechanism for metabolic memory
Chan, P.-S., Kanwar, M., & Kowluru, R. A. (2008) · Journal of Diabetes and its Complications · doi:10.1016/j.jdiacomp.2008.10.002 · Cited by 88
“Reversal of hyperglycemia fails to provide any significant effect on the development of histopathology that is characteristic of diabetic retinopathy and nitrotyrosine continues to accumulate in retinal capillary cells (Engerman & Kern, 1987; Hammes et al., 1993; Kowluru, Kanwar & Kennedy, 2007).”
Background
Diabetic retinopathy, metabolic memory and epigenetic modifications
Kowluru, R. A. (2017) · Vision Research · doi:10.1016/j.visres.2017.02.011 · Cited by 88
Metabolic Memory and Chronic Diabetes Complications: Potential Role for Epigenetic Mechanisms
Intine, R. V. A., & Sarras, M. P. (2012) · Current Diabetes Reports · doi:10.1007/s11892-012-0302-7 · Cited by 89
Diabeteslike Proliferative Retinal Changes in Galactose-Fed Dogs
Kador, P. F. (1995) · Archives of Ophthalmology · doi:10.1001/archopht.1995.01100030108031 · Cited by 88
Perturbed Biochemical Pathways and Associated Oxidative Stress Lead to Vascular Dysfunctions in Diabetic Retinopathy
Mahajan, N., Arora, P., & Sandhir, R. (2019) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2019/8458472 · Cited by 88
“Earlier, an anatomic observation of gradual reduction of capillary cells in DR suggested that “retinopathy neither appears promptly after the onset of hyperglycaemia nor arrests promptly on correction of the hyperglycaemia” [90].”
Background
Capillary Lesions Develop in Retina Rather Than Cerebral Cortex in Diabetes and Experimental Galactosemia
Kern, T. S. (1996) · Archives of Ophthalmology · doi:10.1001/archopht.1996.01100130302013 · Cited by 87
Self-citation
Epigenetic changes in diabetes
Keating, S. T., & El‐Osta, A. (2013) · Clinical Genetics · doi:10.1111/cge.12121 · Cited by 90
“5 years before insulin therapy still developed retinopathy after 5 years of diabetes (29).”
Understanding Metabolic Memory: A Tale of Two Studies
Miller, R. G., & Orchard, T. J. (2020) · Diabetes · doi:10.2337/db19-0514 · Cited by 87
“In animal models, retinal complications (25) continued for 2.”
Background
Re-institution of good metabolic control in diabetic rats and activation of caspase-3 and nuclear transcriptional factor (NF-kB) in the retina
Kowluru, A., Chakrabarti, S. K., & Chen, S. (2004) · Acta Diabetologica · doi:10.1007/s00592-004-0165-8 · Cited by 86
“A study with diabetic dogs has clearly shown that good metabolic control can prevent development of acellular capillaries and microaneurysyms in the retinal microvessels only if it is initiated within a few weeks after the onset of diabetes, but if good control is initiated after a longer duration of poor glycemic con…”
Green Tea Prevents Hyperglycemia-Induced Retinal Oxidative Stress and Inflammation in Streptozotocin-Induced Diabetic Rats
Kumar, B., Gupta, S. K., Nag, T. C., Srivastava, S., & Saxena, R. (2011) · Ophthalmic Research · doi:10.1159/000330051 · Cited by 85
Glucose induced genes in bovine aortic smooth muscle cells identified by mRNA differential display
Nishio, Y., Aiello, L. P., & King, G. L. (1994) · The FASEB Journal · doi:10.1096/fasebj.8.1.8299882 · Cited by 85
“Several lines of evidence have suggested that elevated glucose levels may cause changes in gene expression (3, 4). Clinically, vascular changes occur slowly and are difficult to reverse ( 5 ).”
Background
C-peptide replacement therapy as an emerging strategy for preventing diabetic vasculopathy
Bhatt, M. P., Lim, Y.-C., & Ha, K. (2014) · Cardiovascular Research · doi:10.1093/cvr/cvu211 · Cited by 86
Epigenetics in diabetic nephropathy, immunity and metabolism
Keating, S. T., van Diepen, J. A., Riksen, N. P., & El-Osta, A. (2018) · Diabetologia · doi:10.1007/s00125-017-4490-1 · Cited by 82
Pharmacological approach to diabetic retinopathy
Cruz, J. P. D. L., Correa, J. A. G., Guerrero, A., & Cuesta, M. (2004) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.432 · Cited by 82
“The relationship between elevated glucose values and diabetic retinopathy was initially established in experimental models in animals; [105] nonetheless, definitive evidence was obtained in the Diabetes Control and Complications Trial (DCCT) [23], the Wisconsin Epidemiologic Study of Diabetic Retinopathy [106,107], an…”
Background
Metabolic memory and diabetic retinopathy: Role of inflammatory mediators in retinal pericytes
Kowluru, R. A., Zhong, Q. P. W., & Kanwar, M. (2010) · Experimental Eye Research · doi:10.1016/j.exer.2010.02.006 · Cited by 84
“Animal models of diabetic retinopathy, including chemically induced diabetic rodents and dogs, have successfully mimicked metabolic memory phenomenon (Engerman and Kern 1987; Kowluru 2003).”
Background
Mitochondria Damage in the Pathogenesis of Diabetic Retinopathy and in the Metabolic Memory Associated with its Continued Progression
Kowluru, R. A. (2013) · Current Medicinal Chemistry · doi:10.2174/09298673113209990029 · Cited by 81
Oxidative Stress and Its Regulation in Diabetic Retinopathy
Haydinger, C. D., Oliver, G. F., Ashander, L. M., & Smith, J. R. (2023) · Antioxidants · doi:10.3390/antiox12081649 · Cited by 91
Legacy Effects from DCCT and UKPDS: What They Mean and Implications for Future Diabetes Trials
Murray, P. T., Chune, G., & Raghavan, V. A. (2010) · Current Atherosclerosis Reports · doi:10.1007/s11883-010-0128-1 · Cited by 78
“The first investigation of metabolic memory was reported over a quarter of a century ago by Engerman and Kern [ 22 ].”
Background
Secondary intervention with aminoguanidine retards the progression of diabetic retinopathy in the rat model
Hammes, H., Str�dter, D., Weiss, A., Bretzel, R. G., Federlin, K., & Brownlee, M. (1995) · Diabetologia · doi:10.1007/bf00401835 · Cited by 78
“study also confirms that AGEs that have formed cannot be removed by secondary inhibition 9 Continued progression of diabetic retinopathy after correction of hyperglycaemia or inhibition of A G E formation is consistent with previous descriptions of hyperglycaemic memory [11, 17].”
MethodResult
Degenerated intramural pericytes (‘ghost cells’) in the retinal capillaries of diabetic rats
Robinson, W. G., McCaleb, M. L., Feld, L. G., et al. (1991) · Current Eye Research · doi:10.3109/02713689108996340 · Cited by 78
Simultaneous assessment of stress hyperglycemia ratio and glycemic variability to predict mortality in patients with coronary artery disease: a retrospective cohort study from the MIMIC-IV database
He, H., Zheng, S.-W., Xie, Y., Wang, Z., Jiao, S., Yang, F.-R., Li, X.-X., Li, J., & Sun, Y. (2024) · Cardiovascular Diabetology · doi:10.1186/s12933-024-02146-w · Cited by 81
“Furthermore, this relationship correlated with the intensity and duration of the exposure [46].”
Background
Inhibition of Retinopathy and Retinal Metabolic Abnormalities in Diabetic Rats With AREDS-Based Micronutrients
Kowluru, R. A. (2008) · Archives of Ophthalmology · doi:10.1001/archopht.126.9.1266 · Cited by 77
Diabetic retinopathy: quantitative variation in capillary basement membrane thickening in arterial or venous environments.
Stitt, A. W., Anderson, H. R., Gardiner, T. A., et al. (1994) · British Journal of Ophthalmology · doi:10.1136/bjo.78.2.133 · Cited by 76
Maternal diabetes in vivo and high glucose concentration in vitro increases apoptosis in rat embryos
Gäreskog, M., Cederberg, J., Eriksson, U. J., & Wentzel, P. (2006) · Reproductive Toxicology · doi:10.1016/j.reprotox.2006.08.009 · Cited by 77
An Aldose Reductase Inhibitor and Aminoguanidine Prevent Vascular Endothelial Growth Factor Expression in Rats With Long-term Galactosemia
Frank, R. N. (1997) · Archives of Ophthalmology · doi:10.1001/archopht.1997.01100160206011 · Cited by 75
Epigenetic modifications in metabolic memory: What are the memories, and can we erase them?
Chen, Z., & Natarajan, R. D. (2022) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00201.2022 · Cited by 79
Diabetic retinopathy: Some cellular, molecular and therapeutic considerations
ARCHER, D. B. (1999) · Eye · doi:10.1038/eye.1999.130 · Cited by 70
Aldose reductase: a window to the treatment of diabetic complications?
Crabbe, M. J. C., & Goode, D. (1998) · Progress in Retinal and Eye Research · doi:10.1016/s1350-9462(97)00013-x · Cited by 73
Epigenetic Changes in Endothelial Progenitors as a Possible Cellular Basis for Glycemic Memory in Diabetic Vascular Complications
Rajasekar, P., O’Neill, C. L., Eeles, L., Stitt, A. W., & Medina, R. J. (2015) · Journal of Diabetes Research · doi:10.1155/2015/436879 · Cited by 71
“5 years after diabetes onset did not halt diabetic retinopathy progression, and interestingly retinopathy became evident during the tight glycemic period [1].”
BackgroundInfluential
Advanced glycation and retinal pathology during diabetes.
Stitt, A. W., & Curtis, T. M. (2005) · PubMed · Cited by 70
The role of lipids and protein kinase Cs in the pathogenesis of diabetic retinopathy
Curtis, T. M., & Scholfield, C. N. (2004) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.431 · Cited by 70
“5 years) and in the absence of any overt pathology, subsequent good glycaemic control fails to prevent the development of diabetic complications [67].”
Background
Glycemic Memories and the Epigenetic Component of Diabetic Nephropathy
Keating, S. T., & El‐Osta, A. (2013) · Current Diabetes Reports · doi:10.1007/s11892-013-0383-y · Cited by 71
“Pioneering studies of experimental animal models had suggested memories of prior hyperglycemia [18, 19].”
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Intine, R. V. A., Olsen, A. S., & Sarras, M. P. (2013) · Journal of Visualized Experiments · doi:10.3791/50232 · Cited by 76
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Akirov, A., Diker‐Cohen, T., Masri‐Iraqi, H., & Shimon, I. (2017) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2017-00450 · Cited by 67
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dos Santos, J. M., Mishra, M., & Kowluru, R. A. (2014) · Experimental Eye Research · doi:10.1016/j.exer.2014.02.010 · Cited by 69
“…and diabetic retinopathy continues to progress even after the hyperglycemic insult is terminated, suggesting a ‘metabolic memory’ phenomenon (Engerman and Kern 1987; Diabetes Control and Complications Trial Research Group 1993; Diabetes Control and Complications Trial Research Group 1998;…”
Background
Candidate Genes for Proliferative Diabetic Retinopathy
Petrovič, D. (2013) · BioMed Research International · doi:10.1155/2013/540416 · Cited by 66
“Since the principal pathogenetic mechanisms for diabetic retinopathy (DR) and PDR are different, the main pathogeneticmechanism inDR is increased vascular permeability, whereas in PDR the crucial pathogeneticmechanisms are fibrosis and neoangiogenesis.”
Background
Canine Diabetes Mellitus
Nelson, R. W. (2015) · Elsevier eBooks · doi:10.1016/b978-1-4557-4456-5.00006-7 · Cited by 86
The role of protein kinase C in the development of the complications of diabetes
Ways, D. K., & Sheetz, M. J. (2000) · Vitamins and hormones · doi:10.1016/s0083-6729(00)60019-5 · Cited by 65
Metabolic memory: a vascular perspective
Jax, T. W. (2010) · Cardiovascular Diabetology · doi:10.1186/1475-2840-9-51 · Cited by 65
“Briefly, the first reports of Kern reported two decades ago in a diabetic dog model, that poor glycaemic control followed by a period of good control did show the same rate of retinopathy as poorly controlled dogs [14].”
Background
Epigenetics and Mitochondrial Stability in the Metabolic Memory Phenomenon Associated with Continued Progression of Diabetic Retinopathy
Kowluru, R. A., & Mohammad, G. (2020) · Scientific Reports · doi:10.1038/s41598-020-63527-1 · Cited by 63
Parp Inhibition Prevents Ten-Eleven Translocase Enzyme Activation and Hyperglycemia-Induced DNA Demethylation
Dhliwayo, N., Sarras, M. P., Luczkowski, E., Mason, S. M., & Intine, R. V. A. (2014) · Diabetes · doi:10.2337/db13-1916 · Cited by 64
The Role of DNA Methylation in the Metabolic Memory Phenomenon Associated With the Continued Progression of Diabetic Retinopathy
Mishra, M., & Kowluru, R. A. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.16-19759 · Cited by 64
Legacy effect of intensive glucose control on major adverse cardiovascular outcome: Systematic review and meta-analyses of trials according to different scenarios
Prattichizzo, F., de Candia, P., Nigris, V. D., Nicolucci, A., & Ceriello, A. (2020) · Metabolism · doi:10.1016/j.metabol.2020.154308 · Cited by 65
Normalization of retinal blood flow in diabetic rats with primary intervention using insulin pumps.
Clermont, A. C., Brittis, M., Shiba, T., McGovern, T. J., King, G. L., & Bursell, S. (1994) · PubMed · Cited by 64
Identification and characterization of a gene regulating enzymatic glycosylation which is induced by diabetes and hyperglycemia specifically in rat cardiac tissue.
Nishio, Y., Warren, C. E., Buczek‐Thomas, J. A., Rulfs, J., Koya, D., Aiello, L. P., Feener, E. P., Miller, T. B., Dennis, J. W., & King, G. L. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118221 · Cited by 64
“Since thickening of basement membrane is a classical finding in diabetic microvasculature (10), many of the studies concerning glucose-regulated genes have primarily focused on changes in the basement matrix components using cultured vascular cells (13, 14).”
Background
Long-Term Complications of Diabetes Mellitus, Part I: Retinopathy, Nephropathy, Neuropathy
Muñana, K. R. (1995) · Veterinary Clinics of North America Small Animal Practice · doi:10.1016/s0195-5616(95)50064-6 · Cited by 63
Age at diagnosis predicts deterioration in glycaemic control among children and adolescents with type 1 diabetes
Clements, M. A., Lind, M., Raman, S., Patton, S. R., Lipska, K. J., Fridlington, A., Tang, F., Jones, P. G., Wu, Y. S., Spertus, J. A., et al. (2014) · BMJ Open Diabetes Research & Care · doi:10.1136/bmjdrc-2014-000039 · Cited by 67
Glycemic Control and Diabetic Complications
Strowig, S. M., & Raskin, P. (1992) · Diabetes Care · doi:10.2337/diacare.15.9.1126 · Cited by 63
“The authors concluded that good glycemic control can inhibit the development of diabetic retinopathy, but that this effect is markedly abated if postponed for many months after the onset of diabetes (18).”
BackgroundInfluential
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Leo, M. A. S. D., Caputo, S., Falsini, B., Porciatti, V., Greco, A. V., & Ghirlanda, G. (1994) · Diabetologia · doi:10.1007/bf00400947 · Cited by 62
“Engerman and Kern [50] found that the appearance of retinopathy in diabetic dogs was not related to present control but to previous hyperglycaemia.”
Background
Metabolic memory in diabetes – from in vitro oddity to in vivo problem: Role of Apoptosis
Kowluru, R. A., & Chan, P.-S. (2009) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2009.05.006 · Cited by 62
“Further studies have duplicated this phenomenon in animal models of diabetic retinopathy, including diabetic or experimentally galactosemic dogs and rats, also show this metabolic memory phenomenon [3,9,11,15,18,21,23,24].”
Background
Molecular factors involved in the development of diabetic foot syndrome.
Bruhn‐Olszewska, B., Korzon-Burakowska, A., Gabig‐Cimińska, M., Olszewski, P., Węgrzyn, A., & Jakóbkiewicz‐Banecka, J. (2012) · Acta Biochimica Polonica · doi:10.18388/abp.2012_2085 · Cited by 63
“In addition to the human studies, there is a number of animal studies (Engerman et al., 1987; Hammes et al., 1993; Kowluru et al., 2003) and in vitro cell culture studies (Roy et al., 1990; Ihnat et al., 2007) supporting the metabolic memory hypothesis.”
Background
Continued progression of retinopathy despite spontaneous recovery to normoglycemia in a long-term study of streptozotocin-induced diabetes in rats
Su, E. N., Alder, V. A., Yu, D., et al. (2000) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s004170050028 · Cited by 61
“there is some evidence that the retinopathic changes ay not be reversed by excellent glycemic control or a return to normoglycemia [8, 9].”
Background
Histamine, ZO-1 and increased blood-retinal barrier permeability in diabetic retinopathy.
Gardner, T. W. (1995) · PubMed Central · Cited by 62
Diabetic late complications: Will aldose reductase inhibitors or inhibitors of advanced glycosylation endproduct formation hold promise?
Boel, E., Selmer, J., Flodgaard, H. J., & Jensen, T. J. (1995) · Journal of Diabetes and its Complications · doi:10.1016/1056-8727(94)00025-j · Cited by 60
Diabetic Retinopathy: Retina‐Specific Methods for Maintenance of Diabetic Rodents and Evaluation of Vascular Histopathology and Molecular Abnormalities
Veenstra, A. A., Liu, H., Lee, C. A., Du, Y., Tang, J., & Kern, T. S. (2015) · Current Protocols in Mouse Biology · doi:10.1002/9780470942390.mo140190 · Cited by 59
“Previously, investigators isolated retinal vessels for histologic analysis using the “trypsin digest method” (Kuwabara and Cogan, 1960; Engerman and Kern, 1987; Engerman and Kern, 1993; Kern and Engerman, 1994; Kern and Engerman, 1996), so named because a crude trypsin solution was used as the…”
MethodSelf-citation
Diabetic keratopathy and treatment by modulation of the opioid growth factor (OGF)–OGF receptor (OGFr) axis with naltrexone: A review
McLaughlin, P. J., Sassani, J. W., Klocek, M. S., et al. (2009) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2009.08.008 · Cited by 57
“Clinical [10,61] and laboratory studies [2,27,28] have implicated hyperglycemia in the pathogenesis of long-term complications.”
Background
Oxidative Stress in Preretinopathic Diabetes Subjects and Antioxidants
Nebbioso, M., Federici, M., Rusciano, D., et al. (2011) · Diabetes Technology & Therapeutics · doi:10.1089/dia.2011.0172 · Cited by 57
“27 Recently, Mohammad and Kow-luru 26 demonstrated a signiﬁcant role of retinal mitochondrial damage in the regulation of matrix metalloproteinase type 2 in the development of diabetic retinopathy.”
Aberrant DNA methylation patterns in diabetic nephropathy
Maghbooli, Z., Larijani, B. A., Emamgholipour, S., Amini, M., Keshtkar, A., & Pasalar, P. (2014) · Journal of Diabetes & Metabolic Disorders · doi:10.1186/2251-6581-13-69 · Cited by 58
“There is also an increasing body of evidence to suggest that memory of early hyperglycaemic exposure can be retained in target cells that could subsequently alter gene expression patters even under euglycaemic conditions [27,31-35].”
Background
Diabetic macular edema: review and update
Pelzek, C. D., & Lim, J. I. (2002) · Ophthalmology Clinics of North America · doi:10.1016/s0896-1549(02)00043-3 · Cited by 56
“Early in the development of diabetic retinopathy, degenerative and functional loss of pericytes surrounding retinal capillaries creates a weakness in the capillary wall [13–15].”
Background
The role of hyperglycaemia in the development of diabetic cardiomyopathy
Hayek, M. S. E., Ernande, L., Bénitah, J., Gomez, A. M., & Pereira, L. (2021) · Archives of cardiovascular diseases · doi:10.1016/j.acvd.2021.08.004 · Cited by 58
“Indeed, during cardiomyocyte depolarization, Ca enters into the cell through the L-type voltage-dependent Ca channel, activating a massive release of Ca from the ryanodine receptor of the sarcoplasmic reticulum, which binds to the myoﬁla-ments and generates contraction.”
Background
Bone marrow-CNS connections: Implications in the pathogenesis of diabetic retinopathy
Douglas, J. Y., Bhatwadekar, A. D., Calzi, S. L., Shaw, L. C., Carnegie, D., Caballero, S., Li, Q., Stitt, A. W., Raizada, M. K., & Grant, M. B. (2012) · Progress in Retinal and Eye Research · doi:10.1016/j.preteyeres.2012.04.005 · Cited by 53
“Retinopathy developed in the latter group, despite subsequent sustained good glycaemic control having been achieved (Engerman and Kern, 1987).”
Early Glycation Products Produce Pentosidine Cross-links on Native Proteins
Chellan, P., & Nagaraj, R. H. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m008626200 · Cited by 57
Amino acids and diabetes: implications for endocrine, metabolic and immune function
Newsholme, P. (2010) · Frontiers in bioscience · doi:10.2741/3690 · Cited by 54
“In addition, vascular dysfunction can continue to progress after a hyperglycemic insult despite the subsequent maintenance of normal blood glucose leves (168, 169).”
Background
Etiologic Mechanisms in Diabetic Retinopathy
Frank, R. N. (2006) · Elsevier eBooks · doi:10.1016/b978-0-323-02598-0.50072-0 · Cited by 54
DIABETES CONTROL AND COMPLICATIONS
Crofford, O. B. (1995) · Annual Review of Medicine · doi:10.1146/annurev.med.46.1.267 · Cited by 54
Persistent Insulin Resistance in Podocytes Caused by Epigenetic Changes of SHP-1 in Diabetes
Lizotte, F., Denhez, B., Guay, A., Gévry, N. Y., Côté, A. M., & Geraldes, P. (2016) · Diabetes · doi:10.2337/db16-0254 · Cited by 54
Peptide drug delivery: Colonic and rectal absorption
Mackay, M. W., Phillips, J. A., & Hastewell, J. G. (1997) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(97)00076-8 · Cited by 53
Similarities and differences in early retinal phenotypes in hypertension and diabetes
Grosso, A., Cheung, N., Veglio, F., & Wong, T. Y. (2011) · Journal of Hypertension · doi:10.1097/hjh.0b013e3283496655 · Cited by 52
Visual field loss with capillary non-perfusion in preproliferative and early proliferative diabetic retinopathy.
Chee, C., & Flanagan, D. W. (1993) · British Journal of Ophthalmology · doi:10.1136/bjo.77.11.726 · Cited by 51
Vascular Dysfunction in Hyperglycemia
Gutterman, D. D. (2002) · Circulation Research · doi:10.1161/res.90.1.5 · Cited by 50
Epigenetic mechanisms of hyperglycemic memory
Cencioni, C., Spallotta, F., Greco, S., Martelli, F., Zeiher, A. M., & Gaetano, C. (2014) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2014.04.014 · Cited by 50
Beneficial Effects of Berberine on Oxidized LDL-Induced Cytotoxicity to Human Retinal Müller Cells
Fu, D., Yu, Y., Connell, A. R., Yang, S., Hookham, M. B., McLeese, R. H., & Lyons, T. J. (2016) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.16-19291 · Cited by 49
Acceleration of experimental diabetic retinopathy in the rat by omega-3 fatty acids
Hammes, H. P., Weiss, A., F�hrer, D., Kr�mer, H. J., Papavassilis, C., & Grimminger, F. (1996) · Diabetologia · doi:10.1007/bf00418338 · Cited by 50
Hyperglycemia and Vascular Metabolic Memory: Truth or Fiction?
Bianchi, C., Miccoli, R., & Prato, S. D. (2013) · Current Diabetes Reports · doi:10.1007/s11892-013-0371-2 · Cited by 47
Age and diabetes related changes of the retinal capillaries: An ultrastructural and immunohistochemical study
Bianchi, E., Ripandelli, G., Taurone, S., Fehér, J., Plateroti, R., Kovács, I., Magliulo, G., Orlando, M. P., Micera, A., Battaglione, E., et al. (2015) · International Journal of Immunopathology and Pharmacology · doi:10.1177/0394632015615592 · Cited by 49
Reduction of basement membrane thickening in diabetic cat retina by sulindac.
Mansour, S. Z., Hatchell, D. L., Chandler, D., et al. (1990) · PubMed · Cited by 48
The prevalence of retinopathy in the insulin-requiring diabetic patients of an english country town
McLeod, B. K., Thompson, J., & Rosenthal, A. R. (1988) · Eye · doi:10.1038/eye.1988.77 · Cited by 48
Hypoxic induction of vascular endothelial growth factor is markedly decreased in diabetic individuals who do not develop retinopathy.
Marsh, S., Nakhoul, F. M., Skorecki, K., et al. (2000) · Diabetes Care · doi:10.2337/diacare.23.9.1375 · Cited by 48
Retinopathy in Galactosemic Dogs Continues to Progress After Cessation of Galactosemia
Engerman, R. L. (1995) · Archives of Ophthalmology · doi:10.1001/archopht.1995.01100030111032 · Cited by 48
Self-citation
Irreversible progression of severe retinopathy in young type I insulin-dependent diabetes mellitus patients after improved metabolic control
Agardh, C. –., Eckert, B., & Agardh, E. (1992) · Journal of Diabetes and its Complications · doi:10.1016/1056-8727(92)90018-g · Cited by 47
Prevalence of retinopathy differs with age at onset of diabetes in a population of patients with Type 1 diabetes
Kullberg, C. E., Abrahamsson, M., Arnqvist, H. J., FINNSTRÖM, K. F. O., & Ludvigsson, J. (2002) · Diabetic Medicine · doi:10.1046/j.1464-5491.2002.00839.x · Cited by 47
Arrest of glomerulopathy in diabetic dogs by improved glycaemic control
Kern, T. S., & Engerman, R. L. (1990) · Diabetologia · doi:10.1007/bf00404138 · Cited by 47
“In contrast, little or no retinopathy was present in the same animals at 2.5 years of poor glycaemic control (group P~GC), yet the retinal microangiopathy surprisingly became pronounced during the subsequent 2.5 years of good control [ 13 ].”
BackgroundInfluentialSelf-citation
Blood Glucose Control and Diabetic Microvascular Complications: Long‐term Effects of Near‐normoglycaemia
Hanssen, K. F., Bangstad, H. ‐., Brinchmann-Hansen, O., et al. (1992) · Diabetic Medicine · doi:10.1111/j.1464-5491.1992.tb01876.x · Cited by 47
Functional Regulation of an Oxidative Stress Mediator, Rac1, in Diabetic Retinopathy
Mohammad, G., Duraisamy, A. J., Kowluru, A., & Kowluru, R. A. (2019) · Molecular Neurobiology · doi:10.1007/s12035-019-01696-5 · Cited by 46
The legacy effect in diabetes: are there long-term benefits?
Folz, R., & Laiteerapong, N. (2021) · Diabetologia · doi:10.1007/s00125-021-05539-8 · Cited by 46
Nonenzymatic Glycosylation of Macromolecules: Prospects of Pharmacologic Modulation
Brownlee, M. (1992) · Diabetes · doi:10.2337/diab.41.2.s57 · Cited by 45
Altered endothelial/pericyte ratio in Goto-Kakizaki rat retina
Agardh, C., Agardh, E., Zhang, H., et al. (1997) · Journal of Diabetes and its Complications · doi:10.1016/s1056-8727(96)00049-9 · Cited by 45
The effect of the aldose reductase inhibitor, ponalrestat, on the progression of diabetic retinopathy
Arauz-Pacheco, C., Ramirez, L. C., Pruneda, L., et al. (1992) · Journal of Diabetes and its Complications · doi:10.1016/1056-8727(92)90024-f · Cited by 45

Authors: Engerman, R. L., & Kern, T. S.
Affiliations: University of Wisconsin–Madison (US)
ORCID: Kern, Timothy S
Venue: Diabetes
Publisher: American Diabetes Association
Published: 1987-07-01
Volume: 36
Issue: 7
Pages: 808-812
ISSN: 0012-1797 (ISSN-L)
1939-327X
DOI: 10.2337/diab.36.7.808
OpenAlex: W2104738423
Cited by: 490
References: 0
Citations by year: 2026: 7 · 2025: 10 · 2024: 15 · 2023: 13 · 2022: 12 · 2021: 13 · 2020: 13 · 2019: 16 · 2018: 11 · 2017: 16 · 2016: 14 · 2015: 25 · 2014: 26 · 2013: 22 · 2012: 17
FWCI: 13.21
Type: journal article
Language: en
Open access: closed
Locations: Diabetes (publishedVersion)
PubMed (publishedVersion)
Funders: National Eye Institute (EY00 300)
Topics: Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
Keywords: diabetic retinopathy, disease progression, glycemic control, alloxan-induced diabetes, insulin therapy, HbA1c, glycosuria, retinopathy prevention, dogs
MeSH terms: Aneurysm, Animals, Autopsy, Blood Glucose, Capillaries, Diabetic Retinopathy, Dogs, Female, Hyperglycemia, Insulin, Male, Retina

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Progression of Incipient Diabetic Retinopathy During Good Glycemic Control

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