Charumathi Sabanayagam1,2,3, Weng Kit Lye4, Ronald Klein5, Barbara E K Klein5, Mary Frances Cotch6, Jie Jin Wang7, Paul Mitchell7, Jonathan E Shaw8, Elizabeth Selvin9, A Richey Sharrett9, Tien Y Wong10,11,12. 1. Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore, 168751, Republic of Singapore. 2. Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Republic of Singapore. 3. Department of Ophthalmology, National University of Singapore, Singapore, Republic of Singapore. 4. Centre for Quantitative Medicine, Duke-NUS Graduate Medical School, Singapore, Republic of Singapore. 5. Department of Ophthalmology and Visual Sciences, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA. 6. Division of Epidemiology and Clinical Applications, National Eye Institute, National Institutes of Health, Bethesda, MD, USA. 7. Department of Ophthalmology and Westmead Millennium Institute, Centre for Vision Research, University of Sydney, Sydney, NSW, Australia. 8. Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia. 9. Department of Epidemiology, John Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. 10. Singapore Eye Research Institute, Singapore National Eye Centre, 11 Third Hospital Avenue, Singapore, 168751, Republic of Singapore. ophwty@nus.edu.sg. 11. Ophthalmology and Visual Sciences Academic Clinical Program, Duke-NUS Graduate Medical School, Singapore, Republic of Singapore. ophwty@nus.edu.sg. 12. Department of Ophthalmology, National University of Singapore, Singapore, Republic of Singapore. ophwty@nus.edu.sg.
Abstract
AIMS/HYPOTHESIS: The calibre of the retinal vessels has been linked to diabetes mellitus but studies have not shown consistent results. We conducted a participant-level meta-analysis to evaluate the association between retinal arteriolar and venular calibre and diabetes. METHODS: We performed a systematic review on MEDLINE and EMBASE for articles published up to December 2014. We identified five population-based prospective cohort studies that provided individual-level data on 18,771 diabetes-free participants. We used discrete time proportional hazards models to estimate pooled HRs of diabetes associated with 1 SD (20 μm) change in retinal vascular calibre. RESULTS: We identified 2,581 incident cases of diabetes over a median follow-up period of 10 years (interquartile interval of 3.4-15.8 years). After adjustment for demographic, lifestyle and clinical factors, retinal venular calibre was significantly associated with incident diabetes (pooled HR 1.09 [95% CI 1.02, 1.15] per SD increase in venular calibre). This association persisted in analyses excluding individuals with <5 years of follow-up (1.07 [1.0, 1.12]) or those with impaired fasting glucose at baseline (1.10 [1.03, 1.17]); in subgroup analyses, the association was stronger in men than in women but was consistent across subgroups of race/ethnicity, smoking status, hypertension and BMI categories. Retinal arteriolar calibre was not associated with diabetes (0.95 [0.86, 1.06] per SD decrease in arteriolar calibre). CONCLUSIONS/ INTERPRETATION: Wider retinal venules but not narrower retinal arterioles were associated with a modestly increased risk for diabetes. Knowledge of pathological mechanisms underlying wider retinal venule may provide further insights concerning microvascular alterations in diabetes.
AIMS/HYPOTHESIS: The calibre of the retinal vessels has been linked to diabetes mellitus but studies have not shown consistent results. We conducted a participant-level meta-analysis to evaluate the association between retinal arteriolar and venular calibre and diabetes. METHODS: We performed a systematic review on MEDLINE and EMBASE for articles published up to December 2014. We identified five population-based prospective cohort studies that provided individual-level data on 18,771 diabetes-free participants. We used discrete time proportional hazards models to estimate pooled HRs of diabetes associated with 1 SD (20 μm) change in retinal vascular calibre. RESULTS: We identified 2,581 incident cases of diabetes over a median follow-up period of 10 years (interquartile interval of 3.4-15.8 years). After adjustment for demographic, lifestyle and clinical factors, retinal venular calibre was significantly associated with incident diabetes (pooled HR 1.09 [95% CI 1.02, 1.15] per SD increase in venular calibre). This association persisted in analyses excluding individuals with <5 years of follow-up (1.07 [1.0, 1.12]) or those with impaired fasting glucose at baseline (1.10 [1.03, 1.17]); in subgroup analyses, the association was stronger in men than in women but was consistent across subgroups of race/ethnicity, smoking status, hypertension and BMI categories. Retinal arteriolar calibre was not associated with diabetes (0.95 [0.86, 1.06] per SD decrease in arteriolar calibre). CONCLUSIONS/ INTERPRETATION: Wider retinal venules but not narrower retinal arterioles were associated with a modestly increased risk for diabetes. Knowledge of pathological mechanisms underlying wider retinal venule may provide further insights concerning microvascular alterations in diabetes.
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