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Objective To determine the association between skin intrinsic fluorescence (SIF), a noninvasive measure of advanced glycation endproducts and oxidative stress in skin, and retinal microvascular complications of long duration type 1 diabetes, proliferative diabetic retinopathy (PDR) and macular edema. Research Design and Methods A cross-sectional cohort study of persons with type 1 diabetes in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) who participated in a 32-year follow-up examination in 2012-2014. Subjects underwent physical examination, answered a health questionnaire, and had fundus photographs taken. SIF was measured on the underside of the left forearm near the elbow with the SCOUT DS® skin fluorescence spectrometer. Two representative SIF measures were used for these analyses: SIF01 excited by an LED centered at 375 nm with correction factors Kx=0.6 and Km=0.2 and SIF15 excited by an LED centered at 456 nm with correction factors Kx=0.4 and Km=0.9. Results The 414 participants had mean diabetes duration of 42.2 years (standard deviation 6.8 years, range 32.9- 67.9 years). PDR was statistically significantly associated (p<.05) with both SIF measures in multivariate models including other relevant factors (odds ratio [OR] = 1.17 for SIF01 and 1.20 for SIF15). Conclusion Skin intrinsic fluorescence measures are independently associated with PDR in the WESDR. Incidence information is needed to evaluate whether there is a causal relationship.

AimsTo investigate whether, for a specific duration of type 1 diabetes, there is a significant change in the prevalence of proliferative diabetic retinopathy, gross proteinuria and peripheral neuropathy in those more recently diagnosed with diabetes (a period effect), in the Wisconsin Epidemiologic Study of Diabetic Retinopathy. Where present, to determine how common risk factors for diabetic complications might be associated with it, and what might be driving it.Materials and methodsLongitudinal cohort study with seven examination phases between 1980 and 2014. Multivariate logistic regression models and ordinal parameterization were used to test for and evaluate any period effect.ResultsThere is a period effect in the prevalence of gross proteinuria and peripheral neuropathy (decreasing), as seen with proliferative diabetic retinopathy (p < 0.001). Adjusting for changing levels of common risk factors attenuates the period effect, particularly for proliferative diabetic retinopathy. For gross proteinuria and peripheral neuropathy, however there is a persistent period effect in spite of adjusting for the major risk factors.ConclusionsThere are period effects in the prevalence of proliferative diabetic retinopathy, gross proteinuria and peripheral neuropathy that cannot be fully explained by changes in common risk factors for complications of type 1 diabetes in this cohort. The role of other potential confounders warrants further exploration.

Sensory neuropathy and heartrate variability were significantly associated with prevalent PDR and ME in people with long-term T1D. PDR and ME were significantly associated with incident sensory neuropathy, and sensory neuropathy was significantly associated with incident PDR. Studies using earliest detectable markers of microvascular and neurologic abnormalities are needed to determine which of the two systems 'fails' first. Such information might suggest a temporal sequence of diabetes complications.