Retinal Vessel Calibers Predict Long-term Microvascular Complications in Type 1 Diabetes: The Danish Cohort of Pediatric Diabetes 1987 (DCPD1987)

Abstract

Diabetic neuropathy, nephropathy, and retinopathy cause significant morbidity in patients with type 1 diabetes, even though improvements in treatment modalities delay the appearance and reduce the severity of these complications. To prevent or further delay the onset, it is necessary to better understand common underlying pathogenesis and to discover preclinical biomarkers of these complications. Retinal vessel calibers have been associated with the presence of microvascular complications, but their long-term predictive value has only been sparsely investigated. We examined retinal vessel calibers as 16-year predictors of diabetic nephropathy, neuropathy, and proliferative retinopathy in a young population-based Danish cohort with type 1 diabetes. We used semiautomated computer software to analyze vessel diameters on baseline retinal photos. Calibers of all vessels coursing through a zone 0.5-1 disc diameter from the disc margin were measured and summarized as the central artery and vein equivalents. In multiple regression analyses, we found wider venular diameters and smaller arteriolar diameters were both predictive of the 16-year development of nephropathy, neuropathy, and proliferative retinopathy. Early retinal vessel caliber changes are seemingly early markers of microvascular processes, precede the development of microvascular complications, and are a potential noninvasive predictive test on future risk of diabetic retinopathy, neuropathy, and nephropathy.Diabetic microvascular complications, namely diabetic peripheral neuropathy (DPN), diabetic nephropathy (DN), and diabetic retinopathy (DR), are common in type 1 diabetes (1) despite advances in metabolic care. Identifying new predictors of microvascular disease could be helpful for early individual risk stratification, which may provide better opportunity for timely implementation of effective interventions. For this purpose, the retinal vasculature provides a unique opportunity to assess vascular health directly and noninvasively in vivo.Studies have investigated how retinal vessel calibers are associated with microvascular complications in both type 1 and type 2 diabetes (2-14). The evidence to date suggests that wider retinal venular diameters are associated with presence of both DN and severe levels of DR in several cross-sectional studies (3,(8)(9)(10) and with incident DN (4,5) and progression to severe

The clinical implications of recent studies on the structure and function of the retinal microvasculature in diabetes

“…The findings of this study indicated that the 16 year incidence of diabetic peripheral neuropathy was associated with narrower arteriolar calibre, wider venular calibre and lower fractal dimension at baseline [52,53].…”

“…In the same study, these associations were also confirmed among patients with type 1 diabetes [61]. In the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987) with type 1 diabetes, wider venular calibre, narrower arteriolar calibre and lower fractal dimension measured at baseline were associated with the development of nephropathy at the 16 year follow-up [52,53].…”

“…In contrast, wider arteriolar calibre, but not venular calibre, at baseline was associated with an increased risk of diabetic retinopathy in a study that included 645 Australian children and adolescents with type 1 diabetes [51]. Recently, wider venular calibre, narrower arteriolar calibre and lower fractal dimension measured at baseline were shown to be associated with the 16 year incidence of proliferative diabetic retinopathy in a population-based young Danish cohort with type 1 diabetes [52,53]. For type 2 diabetes, neither arteriolar nor venular calibres has been found to be associated with the incidence or progression of diabetic retinopathy [54,55].…”

Early risk stratification in pediatric type 1 diabetes

“…This thesis provides the longest prospective study to date on both retinal vessel calibres (Broe et al 2014a) and retinal fractal dimensions (Broe et al 2014b) and their predictive value on diabetic microvascular complications.…”

Response to the letter to the editor entitled ‘Assessment of the Triggerfish® contact lens sensor for measurement of intra‐ocular pressure variations’

“…Retinal vascular calibres are important non-invasive biomarkers which are predictive of early-stage (Cheung et al 2008) as well as end-stage diabetic retinopathy (Broe et al 2014). However, observations regarding retinal vascular calibres and diabetic macular oedema (DMO) or DMI are still limited.…”