Original Articles

The role of adiponectin in diabetic retinopathy and insulin resistance

Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Received: 14 May 2025
Published: 7 October 2025
463
Views
361
Downloads
26
HTML

Authors

Diabetic retinopathy (DR) is a common microvascular complication of type 2 diabetes mellitus (T2DM). The pathogenesis of DR is multifactorial, involving chronic hyperglycemia, oxidative stress, inflammation, and insulin resistance (IR), all of which contribute to microvascular damage in the retina. This study aimed to evaluate the role of adiponectin (APN) in DR and its correlation with IR, inflammatory, and glycemic control. A total of 100 T2DM patients were enrolled and equally divided into two groups based on the presence or absence of DR. Demographic characteristics, glycemic indices, IR, inflammatory markers, and serum APN levels were analyzed. The diagnostic performance of APN was assessed using receiver operating characteristic (ROC) curve analysis. Patients with DR had a significantly longer duration of diabetes compared to those without DR (p<0.001). Biochemically, the DR group showed significantly higher levels of fasting blood sugar (p=0.025), hemoglobin A1C (p=0.003), fasting insulin (p=0.005), homeostatic model assessment for IR (p=0.001), and C-reactive protein (p<0.001). Conversely, the median serum APN levels were significantly lower in DR patients (median: 2.65 ng/mL) than in those without DR (median: 5.36 ng/mL; p<0.001). ROC analysis revealed that APN had a fair diagnostic performance for detecting DR (area under the curve: 0.773, 95% confidence interval: 0.679-0.867, p<0.001). DR is associated with poor glycemic control, increased IR, elevated inflammatory markers, and reduced serum APN levels. APN may serve as a potential biomarker for the detection and risk stratification of DR in T2DM patients.

Downloads

Download data is not yet available.

Cheung N, Mitchell P, Wong TY. Diabetic retinopathy. Lancet 2010;376:124-36. DOI: https://doi.org/10.1016/S0140-6736(09)62124-3

Moreno A, Lozano M, Salinas P. Diabetic retinopathy. Nutr Hosp 2013;28:53-6.

Achari AE, Jain SK. Adiponectin, a therapeutic target for obesity, diabetes, and endothelial dysfunction. Int J Mol Sci 2017;18:1321. DOI: https://doi.org/10.3390/ijms18061321

Khoramipour K, Chamari K, Hekmatikar AA, et al. Adiponectin: structure, physiological functions, role in diseases, and effects of nutrition. Nutrients 2021;13:1180. DOI: https://doi.org/10.3390/nu13041180

Kadowaki T, Yamauchi T, Kubota N, et al. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 2006;116:1784-92. DOI: https://doi.org/10.1172/JCI29126

Begum M, Choubey M, Tirumalasetty MB, et al. Adiponectin: a promising target for the treatment of diabetes and its complications. Life 2023;13:2213. DOI: https://doi.org/10.3390/life13112213

Sharma A, Mah M, Ritchie RH, De Blasio MJ. The adiponectin signalling pathway - a therapeutic target for the cardiac complications of type 2 diabetes? Pharmacol Ther 2022;232:108008. DOI: https://doi.org/10.1016/j.pharmthera.2021.108008

Alimi M, Goodarzi MT, Nekoei M. Association of ADIPOQ rs266729 and rs1501299 gene polymorphisms and circulating adiponectin level with the risk of type 2 diabetes in a population of Iran: a case-control study. J Diabetes Metab Disord 2021;20:87-93. DOI: https://doi.org/10.1007/s40200-020-00715-w

Hara K, Boutin P, Mori Y, et al. Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes 2002;51:536-40. DOI: https://doi.org/10.2337/diabetes.51.2.536

Dossarps D, Petit JM, Guiu B, et al. Body fat distribution and adipokine secretion are not associated with diabetic retinopathy in patients with type 2 diabetes mellitus. Ophthalmic Res 2014;51:42-5. DOI: https://doi.org/10.1159/000355323

Mao D, Peng H, Li Q, et al. Aqueous humor and plasma adiponectin levels in proliferative diabetic retinopathy patients. Curr Eye Res 2012;37:803-8. DOI: https://doi.org/10.3109/02713683.2012.676700

Zhao X, An X, Yang C, et al. The crucial role and mechanism of insulin resistance in metabolic disease. Front Endocrinol 2023;14:1149239. DOI: https://doi.org/10.3389/fendo.2023.1149239

American Academy of Ophthalmology. International clinical classification of diabetic retinopathy severity of diabetic macular edema. Available from: https://www.aao.org/education/clinical-statement/international-clinical-classification-system-diabe

Zhang D, Zhang Y, Kang J, Li X. Nonlinear relationship between diabetes mellitus duration and diabetic retinopathy. Sci Rep 2024;14:30223. DOI: https://doi.org/10.1038/s41598-024-82068-5

Voigt M, Schmidt S, Lehmann T, et al. Prevalence and progression rate of diabetic retinopathy in type 2 diabetes patients in correlation with the duration of diabetes. Exp Clin Endocrinol Diabetes 2018;126:570-6. DOI: https://doi.org/10.1055/s-0043-120570

Song P, Yu J, Chan KY, et al. Prevalence, risk factors and burden of diabetic retinopathy in China: a systematic review and meta-analysis. J Glob Health 2018;8:010803. DOI: https://doi.org/10.7189/jogh.08.010803

Lin WJ, Ma XF, Hao M, et al. Liraglutide attenuates the migration of retinal pericytes induced by advanced glycation end products. Peptides 2018;105:7-13. DOI: https://doi.org/10.1016/j.peptides.2018.05.003

Liu WL. MicroRNA-9 inhibits retinal neovascularization in rats with diabetic retinopathy by targeting vascular endothelial growth factor A. J Cell Biochem 2019;120:8032-43. DOI: https://doi.org/10.1002/jcb.28081

Zhang X, Zhao J, Zhao T, Liu H. Effects of intensive glycemic control in ocular complications in patients with type 2 diabetes: a meta-analysis of randomized clinical trials. Endocrine 2015;49:78-79. DOI: https://doi.org/10.1007/s12020-014-0459-8

Azad N, Agrawal L, Bahn G, et al. Eye outcomes in veteran affairs diabetes trial (VADT) after 17 years. Diabetes Care 2021;44:2397-402. DOI: https://doi.org/10.2337/dc20-2882

Ipp E, Kumar M. A clinical conundrum: intensifying glycemic control in the presence of advanced diabetic retinopathy. Diabetes Care 2021;44:2192-3. DOI: https://doi.org/10.2337/dci21-0029

Li Y, Liu Y, Liu S, et al. Diabetic vascular diseases: molecular mechanisms and therapeutic strategies. Signal Transduct Target Ther 2023;8:152. DOI: https://doi.org/10.1038/s41392-023-01400-z

Chen J, Wu K, Lin Y, et al. Association of triglyceride glucose index with all-cause and cardiovascular mortality in the general population. Cardiovasc Diabetol 2023;22:320. DOI: https://doi.org/10.1186/s12933-023-02054-5

Tan L, Liu Y, Liu J, et al. Association between insulin resistance and uncontrolled hypertension and arterial stiffness among US adults: a population-based study. Cardiovasc Diabetol 2023;22:311. DOI: https://doi.org/10.1186/s12933-023-02038-5

Bao YK, Yan Y, Wilson B, et al. Association of retinopathy and insulin resistance: NHANES 2005-2008. Curr Eye Res 2020;45:173-6. DOI: https://doi.org/10.1080/02713683.2019.1659977

Choi EY, Park SE, Lee SC, et al. Association between clinical biomarkers and optical coherence tomography angiography parameters in type 2 diabetes mellitus. Invest Ophthalmol Visual Sci 2020;61:4. DOI: https://doi.org/10.1167/iovs.61.3.4

Zheng Z, Yan M, Zhang D, et al. Quantitatively evaluating the relationships between insulin resistance and retinal neurodegeneration with optical coherence tomography in early type 2 diabetes mellitus. Ophthalmic Res 2023;66:968-77. DOI: https://doi.org/10.1159/000530904

Chase HP, Cooper S, Osberg I, et al. Elevated C-reactive protein levels in the development of type 1 diabetes. Diabetes 2004;53:2569-73. DOI: https://doi.org/10.2337/diabetes.53.10.2569

Song J, Chen S, Liu X, et al. Relationship between C-reactive protein level and diabetic retinopathy: a systematic review and meta-analysis. PLoS One 2015;10:e0144406. DOI: https://doi.org/10.1371/journal.pone.0144406

Qiu F, Ma X, Shin YH, et al. Pathogenic role of human C-reactive protein in diabetic retinopathy. Clin Sci 2020;134:1613-29. DOI: https://doi.org/10.1042/CS20200085

Yang HS, Choi YJ, Han HY, et al. Serum and aqueous humor adiponectin levels correlate with diabetic retinopathy development and progression. PLoS One 2021;16:e0259683. DOI: https://doi.org/10.1371/journal.pone.0259683

Yang HS, Choi YJ, Han HY, et al. The relationship between retinal and choroidal thickness and adiponectin concentrations in patients with type 2 diabetes mellitus. Invest Ophthalmol Vis Sci 2023;64:6. DOI: https://doi.org/10.1167/iovs.64.4.6

Rodríguez AJ, Nunes Vdos S, Mastronardi CA, et al. Association between circulating adipocytokine concentrations and microvascular complications in patients with type 2 diabetes mellitus: A systematic review and meta-analysis of controlled cross-sectional studies. J Diabetes Complications 2016;30:357-67. DOI: https://doi.org/10.1016/j.jdiacomp.2015.11.004

Achari AE, Jain SK. Adiponectin, a therapeutic target for obesity, diabetes, and endothelial dysfunction. Int J Mol Sci 2017;18:1321. DOI: https://doi.org/10.3390/ijms18061321

Deng H, Ai M, Cao Y, et al. Potential protective function of adiponectin in diabetic retinopathy. Ophthalmol Ther 2023;12:1519-34. DOI: https://doi.org/10.1007/s40123-023-00702-3

Fu Z, Gong Y, Löfqvist C, et al. Review: adiponectin in retinopathy. Biochim Biophys Acta 2016;1862:1392-400. DOI: https://doi.org/10.1016/j.bbadis.2016.05.002

How to Cite



The role of adiponectin in diabetic retinopathy and insulin resistance. (2025). Italian Journal of Medicine, 19(4). https://doi.org/10.4081/itjm.2025.2049