Abstract
Background:
The aim of the study was to describe the relationship of retinal arteriolar and venular calibre with vascular risk factors in children and adolescents with type 1 diabetes.
Methods:
In this hospital-based cross-sectional study, the medical files of 483 children and adolescents with type 1 diabetes were audited to collect retinal images and relevant clinical data. Retinal vascular calibre was measured using standardised protocols.
Results:
After multivariable adjustments, a vascular risk profile that included: older age, higher serum creatinine, higher systolic blood pressure (SBP), higher body mass index (BMI), abnormal estimated glomerular filtration rate (eGFR), lower high-density lipoproteins (HDL) cholesterol, longer duration of diabetes and higher serum sodium was associated with narrower central retinal artery equivalent (CRAE) (95% CI=−4.10/−0.76, p=0.004). A specific risk profile, including higher total cholesterol level, higher BMI, lower physical activity level, higher HbA1c, higher triglyceride levels, female gender and lower socio-economic status, was associated with wider central retinal vein equivalent (CRVE) (95% CI=1.14/5.62, p=0.003).
Conclusions:
In summary, these findings support evidence that cardiovascular disease may have its origins early in life. Prospective and/or intervention studies are required to confirm whether the observed associations are involved in the causal pathway for retinal vascular calibre.
Acknowledgments:
The authors would like to acknowledge the support of staff within the diabetes clinic at the Royal Children’s Hospital, Melbourne, Victoria, Australia during data collection for this project. Furthermore, the authors would like to thank the grading team at the Centre for Eye Research Australia for providing retinal vascular calibre grading training for the student researcher of this project.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: None declared.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
References
1. Cheung N, Islam A, Saw S, Shankar A, De Haseth K, et al. Distribution and associations of retinal vascular caliber with ethnicity, gender, and birth parameters in young children. Invest Ophthalmol Vis Sci 2007;48:1018–24.10.1167/iovs.06-0978Search in Google Scholar PubMed
2. Sun C, Wang J, Mackey D, Wong T. Retinal vascular caliber: systemic, environmental, and genetic associations. Surv Ophthalmol 2009;54:74–95.10.1016/j.survophthal.2008.10.003Search in Google Scholar PubMed
3. Taarnhoj N, Larson M, Sander B, Kyvik K, Kessel L, et al. Heritability of retinal vessel diameters and blood pressure: a twin study. Invest Ophthalmol Vis Sci 2006;47:3539–44.10.1167/iovs.05-1372Search in Google Scholar PubMed
4. Wang J, Wong T. Genetic determinants of retinal vascular caliber: additional insights into hypertension pathogenesis. Hypertension 2006;47:644–5.10.1161/01.HYP.0000208303.74884.78Search in Google Scholar PubMed
5. Serre K, Sasongko M. Modifiable lifestyle and environmental risk factors affecting microcirculation. Microcirculation 2011;19:29–36.10.1111/j.1549-8719.2011.00121.xSearch in Google Scholar PubMed
6. Liew G, Wang J, Mitchell P, Wong T. Retinal vascular imaging: a new tool in microvascular disease research. Circ Cardiovasc Imaging 2008;1:156–61.10.1161/CIRCIMAGING.108.784876Search in Google Scholar PubMed
7. McGeechen K, Liew G, Macaskill P, Irwig L, Klein R, et al. Prediction of incident stroke events on retinal vascular caliber: a systematic review and individual-participant meta-analysis. Am J Epidemiol 2009;170:1323–32.10.1093/aje/kwp306Search in Google Scholar PubMed PubMed Central
8. McGeechen K, Liew G, Macaskill P, Irwig L, Klein R, et al. Risk prediction of coronary heart disease based on retinal vascular caliber. Am J Cardiol 2008;102:58–63.10.1016/j.amjcard.2008.02.094Search in Google Scholar PubMed PubMed Central
9. Alibrahim E, Donaghue K, Rogers S, Hing S, Jenkins A, et al. Retinal vascular caliber and risk of retinopathy in young patients with type 1 diabetes. Ophthalmol 2006;113:1499–503.10.1016/j.ophtha.2006.05.009Search in Google Scholar PubMed
10. Benitez-Aguirre P, Craig M, Bayu Sasongko M, Jenkins A, Wong T, et al. Retinal vascular geometry predicts incident retinopathy in young people with type 1 diabetes. Diabetes Care 2011;34:1622–7.10.2337/dc10-2419Search in Google Scholar PubMed PubMed Central
11. Cheung N, Rogers S, Donaghue K, Jenkins A, Tikellis G, et al. Retinal arteriolar dilation predicts retinopathy in adolescents with type 1 diabetes. Diabetes Care 2008;31:1842–6.10.2337/dc08-0189Search in Google Scholar PubMed PubMed Central
12. Falck A, Laatikainen L. Retinal vasodilation and hyperglycaemia in diabetic children and adolescents. Acta Ophthalmol 1995;73:119–24.10.1111/j.1600-0420.1995.tb00650.xSearch in Google Scholar PubMed
13. Rogers S, Tikellis G, Cheung N, Tapp R. Retinal arteriolar caliber predicts incident retinopathy: the Australian diabetes, obesity and lifestyle (AusDiab) study. Diabetes Care 2008;31:761–3.10.2337/dc07-1622Search in Google Scholar PubMed
14. Sasongko M, Wang J, Donaghue K, Cheung N, Benitez-Aguirre P, et al. Alterations in retinal microvascular geometry in young type 1 diabetes. Diabetes Care 2010;33:1331–6.10.2337/dc10-0055Search in Google Scholar PubMed PubMed Central
15. Broe R, Rasmussen M, Frydkjaer-Olsen U, Mortensen H, Hodgson L, et al. Retinal vessel calibers predict long-term microvascular complications in type 1 diabetes: the Danish Cohort of Pediatric Diabetes 1987. Diabetes 2014;63:3606–14.10.2337/db14-0227Search in Google Scholar PubMed
16. Mitchell P, Cheung N, De Haseth K, Taylor B, Rochtchina E, et al. Blood pressure and retinal arteriolar narrowing in children. Hypertension 2007;49:1156–62.10.1161/HYPERTENSIONAHA.106.085910Search in Google Scholar PubMed
17. Gopinath B, Baur L, Teber E, Liew G, Wong T, et al. Effect of obesity on retinal vascular structure in pre-adolescent children. Int J Pediatr Obes 2011;6:353–9.10.3109/17477166.2010.500390Search in Google Scholar PubMed
18. Mitchell P, Liew G, Rochtchina E, Wang J, Robaei D, et al. Evidence of arteriolar narrowing in low-birth-weight children. Circulation 2008;118:518–24.10.1161/CIRCULATIONAHA.107.747329Search in Google Scholar PubMed
19. Sun C, Ponsonby A, Wong T, Brown S, Kearn L, et al. Effect of birth parameters on retinal vascular caliber: the twins eye study in Tasmania. Hypertension 2009;53:487–93.10.1161/HYPERTENSIONAHA.108.125914Search in Google Scholar PubMed
20. Cheung N, Saw S, Islam A, Rogers S, Shankar A, et al. BMI and retinal vascular caliber in children. Obesity 2006;15:209–15.10.1038/oby.2007.576Search in Google Scholar PubMed
21. ABS. Socio-economic indexes for areas: technical paper. http://www.abs.gov.au: Australian Bureau of Statistics, 2011.Search in Google Scholar
22. Keel S, Itsiopoulos C, Koklanis K, Vukicevic M, Cameron F, et al. Dietary patterns and retinal vascular calibre in children and adolescents with type 1 diabetes. Acta Ophthalmol 2016;94:345–52.10.1111/aos.12941Search in Google Scholar
23. Staples A, LeBlond R, Watkins S, Wong C, Brandt J. Validation of the revised Schwartz estimating equation in a predominantly non-CKD population. Pediat Nephrol 2010;25:2321–6.10.1007/s00467-010-1598-7Search in Google Scholar
24. Group ETDRS. Grading diabetic retinopathy from stereoscopic color fundus photographs – an extension of the modified Airlie House classification. Ophthalmol 1991;98:786–806.10.1016/S0161-6420(13)38012-9Search in Google Scholar
25. Wong T, Knudtson M, Klein R, Klein B, Meuer S, et al. Computer-assisted measurement of retinal vessel diameters in the Beaver Dam eye study: methodology, correlation between eyes, and effect of refractive errors. Ophthalmology 2004;111:1183–90.10.1016/j.ophtha.2003.09.039Search in Google Scholar
26. Hubbard L, Brothers R, King G, Clegg L, Klein R, et al. Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the atherosclerosis risk in communities study. Ophthalmol 1999;106:2269–80.10.1016/S0161-6420(99)90525-0Search in Google Scholar
27. Knudtson M, Lee K, Hubbard L, Wong T, Klein R, et al. Revised formulas for summarising retinal vessel diameters. Curr Eye Res 2003;27:143–9.10.1076/ceyr.27.3.143.16049Search in Google Scholar
28. Wong T, Islam A, Klein R. Retinal vascular caliber, cardiovascular risk factors, and inflammation: the multi-ethnic study of atherosclerosis (MESA). Invest Ophthalmol Vis Sci 2006;47:2341–50.10.1167/iovs.05-1539Search in Google Scholar
29. Yau J, Xie J, Lamoureux E, Klein R, Klein B, et al. Retinal microvascular calibre and risk of incident diabetes: the multi-ethnic study of atherosclerosis. Diabetes Res Clin Pract 2012;95: 265–74.10.1016/j.diabres.2011.10.027Search in Google Scholar
30. Klein R, Klein B, Moss S, Wong T, Hubbard L, et al. Retinal vascular abnormalities in persons with type 1 diabetes. Ophthalmol 2003;90:2118–24.10.1016/S0161-6420(03)00863-7Search in Google Scholar
31. Klein R, Klein B, Moss S, Wong T, Sharrett A. Retinal vascular caliber in persons with type 2 diabetes. Ophthalmol 2006;13:1488–96.10.1016/j.ophtha.2006.03.028Search in Google Scholar PubMed
32. Klein R, Myers K, Klein B, Zinman B, Gardiner R, et al. Relationship of blood pressure to retinal vessel diameter in type 1 diabetes mellitus. Arch Ophthalmol 2010;128:198–205.10.1001/archophthalmol.2009.391Search in Google Scholar
33. Wong T, Klein R, Sharrett A, Duncan B, Couper D, et al. Retinal arteriolar diameter and risk for hypertension. Ann Intern Med 2004;140:248–55.10.7326/0003-4819-140-4-200402170-00006Search in Google Scholar
34. Wong T, Shankar A, Klein R, Klein B, Hubbard L. Retinal arteriolar narrowing, hypertension, and subsequent risk of diabetes mellitus. Arch Intern Med 2005;165:1060–5.10.1001/archinte.165.9.1060Search in Google Scholar
35. Wong T, Coresh J, Klein R. Retinal microvascular abnormalities and renal dysfunction:the atherosclerosis risk in communities study. J Am Soc Nephrol 2004;15:2469–76.10.1097/01.ASN.0000136133.28194.E4Search in Google Scholar
36. Witt N, Wong T, Hughes A, Chaturvedi N, Klein B, et al. Abnormalities in retinal microvascular structure and risk of mortality from ischemic heart disease and stroke. Hypertension 2002;47:975–81.10.1161/01.HYP.0000216717.72048.6cSearch in Google Scholar
37. Sharrett A, Hubbard L, Cooper L, Sorlie P, Brothers R, et al. Retinal arteriolar diameters and elevated blood pressure: the cardiovascular health study. Am J Epidemiol 1999;150:263–70.10.1093/oxfordjournals.aje.a009997Search in Google Scholar
38. Tso M, Jampol L. Pathophysiology of hypertensive retinopathy. Ophthalmol 1982;89:1132–45.10.1016/S0161-6420(82)34663-1Search in Google Scholar
39. Wang J, Mitchell P, Leung H, Rochtchina E, Wong T, et al. Hypertensive retinal vessel wall signs in a general older population: the Blue Mountains eye study. Hypertension 2003;42:534–41.10.1161/01.HYP.0000090122.38230.41Search in Google Scholar PubMed
40. Wong T, Shankar A, Klein R, Klein B. Retinal vessel diameters and the incidence of gross proteinuria and renal insufficiancy in people with type 1 diabetes. Diabetes 2004;53:179–84.10.2337/diabetes.53.1.179Search in Google Scholar PubMed
41. Grauslund J, Hodgson L, Kawasaki R, Green A, Sjolie A, et al. Retinal vessel calibre and micro- and macrocirculation complications in type 1 diabetes. Diabetologia 2009;52:2213–7.10.1007/s00125-009-1459-8Search in Google Scholar PubMed
42. Bastard J, Jardel C, Brucket E. Elevated levels of interleukin-6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. J Clin Endocrinol Metab 2000;85:3338–42.Search in Google Scholar
43. Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, et al. Effect of weight loss and lifestyle on vascular inflammatory markers in obese women. J Am Med Assoc 2003;289:1799–804.10.1001/jama.289.14.1799Search in Google Scholar PubMed
44. Kasapis C, Thomson P. The effects of physical activity on serum C-reactive protien and inflammatory markers: a systematic review. J Am Coll Cardiol 2005;45:1563–9.10.1016/j.jacc.2004.12.077Search in Google Scholar PubMed
45. Mora S, Cook N, Buring J, Ridker P, Lee I. Physical activity and reduced risk of cardiovascular events: potential mediating mechanisms. Circulation 2007;116:2110–8.10.1161/CIRCULATIONAHA.107.729939Search in Google Scholar PubMed PubMed Central
46. Ouchi N, Kihara S, Funahashi T, Matsuzawa Y, Walsh K. Obesity, adeponectin and vascular inflammatory disease. Curr Opin Lipidol 2003;14:561–6.10.1097/00041433-200312000-00003Search in Google Scholar PubMed
47. Cheung C, Zheng Y, Hsu W, Lee J, Lau Q, et al. Retinal vascular toruosity, blood pressure, and cardiovascular risk factors. Ophthalmol 2011;118:812–8.10.1016/j.ophtha.2010.08.045Search in Google Scholar PubMed
48. Ikram M, De Jong F, Vingerling J, Witteman M, Hofman A, et al. Are retinal arteriolar or venular diameters associated with markers for cardiovascular disorders? the Rotterdam study. Invest Ophthalmol Vis Sci 2004;45:2129–34.10.1167/iovs.03-1390Search in Google Scholar PubMed
©2017 Walter de Gruyter GmbH, Berlin/Boston
