Retinal Vessel Diameters and the Incidence of Gross Proteinuria and Renal Insufficiency in People With Type 1 Diabetes

Abstract

Early retinal vessel caliber changes may predict risk of diabetic nephropathy. We examined the association of retinal vessel diameters and the incidence of gross proteinuria and renal insufficiency in a populationbased cohort of people with type 1 diabetes (n ‫؍‬ 557). Baseline retinal photographs were digitized, and diameters of individual retinal vessels were measured and summarized. Incident cases of gross proteinuria and renal insufficiency were identified over a 16-year period. Larger retinal venular diameter was associated with higher cumulative incidence of gross proteinuria (18.6, 25.4, 37.7, and 50.4%, comparing increasing venular diameter quartiles) and renal insufficiency (10. A lthough diabetes accounts for 42% of end-stage renal disease in the U.S. (1), current methods to predict people at risk of diabetic nephropathy remain inadequate (2,3). Microangiopathy is believed to be a key pathogenic mechanism in the development of diabetic nephropathy (4 -6), and approaches that identify early stages of microvascular disease may potentially provide information regarding risk of this complication in individuals with diabetes.The retinal microcirculation, accessible to direct noninvasive visualization, shares similar physiological and pathological characteristics with the renal microcirculation (7-9). Previous studies have documented the strong association between advanced stages of diabetic retinal disease (e.g., proliferative retinopathy) and nephropathy (10 -15). However, the relationship of early retinal vessel caliber changes (e.g., arteriolar narrowing and venular dilatation) and risk of diabetic nephropathy is unknown, although altered retinal blood flow is clearly linked with the pathogenesis of diabetes (16 -22).In the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), a population-based study of people with diabetes, we recently used a computer-assisted method to measure retinal vessel diameters from digitized fundus photographs (23). We have shown that narrowed retinal arterioles and dilated venules were related to severity of diabetic retinopathy, independent of duration of disease, glycemic control, blood pressure, and other risk factors. In the current study, we prospectively examine the association of retinal arteriolar and venular diameters and the 16-year incidence of gross proteinuria and renal insufficiency in the WESDR cohort. RESEARCH DESIGN AND METHODSThe WESDR has been described in detail in earlier publications (24,25). In brief, a probability sample of 10,135 diabetic patients who received primary care in an 11-county area in southern Wisconsin from 1979 to 1980, composed of "younger-onset" and "older-onset" individuals, was invited to participate in the baseline examination conducted from 1980 to 1982 (24,25). These analyses will be limited to the group of younger-onset individuals who were taking insulin and had been diagnosed before 30 years of age (n ϭ 1,210). The second examination was conducted at 4 years (1984 -1986) (26), the third at 10 years (1990 -1992) (27...

The relationship of retinal vascular calibre to diabetes and retinopathy: the Australian Diabetes, Obesity and Lifestyle (AusDiab) study

“…Both cross-sectional and prospective data from the Wisconsin Epidemiological Study of Diabetic Retinopathy (WESDR) [10,34] show that wider venular calibre is associated with severity and progression of retinopathy and with other microvascular complications, such as gross proteinuria and nephropathy [11]. However, despite the consistency of our study findings with the WESDR, the biological mechanisms that underlie these associations are uncertain, and may reflect increased retinal blood flow secondary to a combination of hyper-glycaemia [35] retinal hypoxia [9,36], inflammation [37], increased lactate production [38] and/or endothelial dysfunction [39].…”

“…Using these new methods, several studies have shown that changes in retinal vascular calibre are associated with the risk of developing type 2 diabetes [7,8] and impaired fasting glucose (IFG) [9] and, among people with diabetes, with progression of retinopathy [10] and nephropathy [11]. However, there is a significant gap in the current literature concerning a clear understanding of how retinal vascular calibre changes with increasing severity of glucose intolerance [12].…”

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

“…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 DR (13,14) in prospective studies. No relations between retinal venular diameters and DPN have been shown thus far (2,4,6,7).…”

“…Studies have investigated how retinal vessel calibers are associated with microvascular complications in both type 1 and type 2 diabetes (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(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 DR (13,14) in prospective studies.…”

Retinal vascular fractals predict long-term microvascular complications in type 1 diabetes mellitus: the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987)

“…Measurements of vessel calibres in retinal photos could potentially deliver such biomarkers [3][4][5][6][7], but more global variables are available, for example retinal vascular fractal dimensions. The fractal dimension summarises the complexity and density of branching structures characterised by selfsimilarity and a similar level of complexity despite changes in magnification (for example snowflakes, tree branches, lightning).…”