The Influence of Insulin on Diabetic Retinopathy and Retinal Vessel Parameters in Diabetes

Overview

Journal Diabetol Metab Syndr

Publisher Biomed Central

Specialty Endocrinology

Date 2024 Sep 29

PMID 39343944

Authors

Tianyi Yuan

Senlin Lin

Yi Xu

Lina Lu

Minna Cheng

Yuheng Wang

Qinping Yang

Saiguang Ling

Dengji Zhou

Yan Shi

Haidong Zou

Yingyan Ma

Affiliations

Soon will be listed here.

Abstract

Aim: To investigate the associations between insulin use and diabetic retinopathy (DR), and retinal vascular parameters in type 2 diabetes (T2DM).

Methods: A total of 6,374 T2DM patients, consisting of 2,231 patients receiving insulin alone and 4143 patients without any hypoglycemic medication, were included in cross-sectional analyses. Among those without DR at baseline, 791 patients were followed for three years in longitudinal analyses. Fundus photography was taken to diagnose DR and calculate central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), arteriolar-to-venular ratio (AVR), and vascular tortuosity. Inverse probability treatment-weighted analyses were performed.

Results: After adjusting for gender, age, body mass index, blood pressure, blood glucose, T2DM duration, smoking, and alcohol use, insulin users showed a higher risk of DR (odds ratio (OR) = 2.27, 95% confidence interval (95%CI) = 2.08-2.48, P < 0.001), larger CRVE (β = 3.92, 95%CI = 2.46-5.37, P < 0.001), smaller AVR (β=-0.0083, 95%CI=-0.0121- -0.0046, P < 0.001), and larger vascular curvature (β = 0.19, 95%CI = 0.05-0.33, P = 0.008). After 3 years, insulin users had a higher risk of developing DR (OR = 1.94; 95% CI = 1.37-2.73, P = 0.002), and greater change in CRVE (β = 3.92, 95%CI = 0.96-6.88, P = 0.009).

Conclusions: The impact of insulin on the retinal microvasculature provides support for linking insulin to the increased risk of DR, as well as cardiovascular events in T2DM.

References

. 10. Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2021; 45(Suppl 1):S144-S174. DOI: 10.2337/dc22-S010. View

. 6. Glycemic Targets: Standards of Medical Care in Diabetes-2022. Diabetes Care. 2021; 45(Suppl 1):S83-S96. DOI: 10.2337/dc22-S006. View

Wilkinson C, Ferris 3rd F, Klein R, Lee P, Agardh C, Davis M . Proposed international clinical diabetic retinopathy and diabetic macular edema disease severity scales. Ophthalmology. 2003; 110(9):1677-82. DOI: 10.1016/S0161-6420(03)00475-5. View

Li X, Tan T, Wong T, Sun X . Diabetic retinopathy in China: Epidemiology, screening and treatment trends-A review. Clin Exp Ophthalmol. 2023; 51(6):607-626. DOI: 10.1111/ceo.14269. View

Allon R, Aronov M, Belkin M, Maor E, Shechter M, Fabian I . Retinal Microvascular Signs as Screening and Prognostic Factors for Cardiac Disease: A Systematic Review of Current Evidence. Am J Med. 2020; 134(1):36-47.e7. DOI: 10.1016/j.amjmed.2020.07.013. View

LeRoith D, Biessels G, Braithwaite S, Casanueva F, Draznin B, Halter J . Treatment of Diabetes in Older Adults: An Endocrine Society* Clinical Practice Guideline. J Clin Endocrinol Metab. 2019; 104(5):1520-1574. PMC: 7271968. DOI: 10.1210/jc.2019-00198. View

Zhang P, Xue W, Huang X, Xu Y, Lu L, Zheng K . Prevalence and risk factors of diabetic retinopathy in patients with type 2 diabetes in Shanghai. Int J Ophthalmol. 2021; 14(7):1066-1072. PMC: 8243199. DOI: 10.18240/ijo.2021.07.16. View

Su E, Yu D, Alder V, Cringle S, Yu P . Direct vasodilatory effect of insulin on isolated retinal arterioles. Invest Ophthalmol Vis Sci. 1996; 37(13):2634-44. View

Siegrist M, Hanssen H, Neidig M, Fuchs M, Lechner F, Stetten M . Association of leptin and insulin with childhood obesity and retinal vessel diameters. Int J Obes (Lond). 2013; 38(9):1241-7. DOI: 10.1038/ijo.2013.226. View

10.

Gishti O, Jaddoe V, Hofman A, Wong T, Ikram M, Gaillard R . Body fat distribution, metabolic and inflammatory markers and retinal microvasculature in school-age children. The Generation R Study. Int J Obes (Lond). 2015; 39(10):1482-7. DOI: 10.1038/ijo.2015.99. View

11.

Klein R, Klein B, Knudtson M, Wong T, Tsai M . Are inflammatory factors related to retinal vessel caliber? The Beaver Dam Eye Study. Arch Ophthalmol. 2006; 124(1):87-94. DOI: 10.1001/archopht.124.1.87. View

12.

Agoritsas T, Merglen A, Shah N, ODonnell M, Guyatt G . Adjusted Analyses in Studies Addressing Therapy and Harm: Users' Guides to the Medical Literature. JAMA. 2017; 317(7):748-759. DOI: 10.1001/jama.2016.20029. View

13.

Zhou J, Koska J, Bahn G, Reaven P . Fasting Glucose Variation Predicts Microvascular Risk in ACCORD and VADT. J Clin Endocrinol Metab. 2020; 106(4):1150-1162. PMC: 7993576. DOI: 10.1210/clinem/dgaa941. View

14.

Gunnlaugsdottir E, Halldorsdottir S, Klein R, Eiriksdottir G, Klein B, Benediktsson R . Retinopathy in old persons with and without diabetes mellitus: the Age, Gene/Environment Susceptibility--Reykjavik Study (AGES-R). Diabetologia. 2011; 55(3):671-80. PMC: 3269506. DOI: 10.1007/s00125-011-2395-y. View

15.

Song P, Yu J, Chan K, Theodoratou E, Rudan I . Prevalence, risk factors and burden of diabetic retinopathy in China: a systematic review and meta-analysis. J Glob Health. 2018; 8(1):010803. PMC: 5997368. DOI: 10.7189/jogh.08.010803. View

16.

Liew G, Benitez-Aguirre P, Craig M, Jenkins A, Hodgson L, Kifley A . Progressive Retinal Vasodilation in Patients With Type 1 Diabetes: A Longitudinal Study of Retinal Vascular Geometry. Invest Ophthalmol Vis Sci. 2017; 58(5):2503-2509. DOI: 10.1167/iovs.16-21015. View

17.

Lin Z, Wen L, Wang Y, Li D, Zhai G, Moonasar N . Incidence, progression and regression of diabetic retinopathy in a northeastern Chinese population. Br J Ophthalmol. 2022; . DOI: 10.1136/bjo-2022-321384. View

18.

Kida T, Oku H, Horie T, Matsuo J, Kobayashi T, Fukumoto M . NADPH Oxidase-Mediated ROS Production Determines Insulin's Action on the Retinal Microvasculature. Invest Ophthalmol Vis Sci. 2015; 56(11):6754-61. DOI: 10.1167/iovs.15-17534. View

19.

Long T, Xu Y, Zou H, Lu L, Yuan T, Dong Z . A Generic Pixel Pitch Calibration Method for Fundus Camera via Automated ROI Extraction. Sensors (Basel). 2022; 22(21). PMC: 9653591. DOI: 10.3390/s22218565. View

20.

Feldman-Billard S, Larger E, Massin P . Early worsening of diabetic retinopathy after rapid improvement of blood glucose control in patients with diabetes. Diabetes Metab. 2017; 44(1):4-14. DOI: 10.1016/j.diabet.2017.10.014. View