Neural dysfunction and retinopathy in persons with type 1 diabetes.

OBJECTIVE: To determine associations of microvascular and neuropathic complications of diabetes cross-sectionally and longitudinally in persons with long-term type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: Persons receiving care for T1D in South Central Wisconsin were identified in 1979-1980 and examined approximately every 5 years. Associations between neuropathic and microvascular complications were examined at most prior visits, when information on several neuropathic complications was collected. Temporal relationships were examined by modeling incidence between examinations across the visits. RESULTS: Adjusting for duration of diabetes, glycated hemoglobin, and systolic blood pressure, the following were cross-sectionally associated with prevalent PDR (proliferative diabetic retinopathy): the presence of sensory neuropathy (SN) as reported at each Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) examination (odds ratio (OR) = 2.76, confidence interval (CI) = 1.71, 4.48) and the heartrate variability measures RMSD (square root of the mean of squared differences of successive RR intervals) (OR = 0.24, CI = 0.16, 0.37) and SDNN (standard deviation of successive RR intervals) (OR = 0.26, CI = 0.17, 0.39). Findings were similar for prevalent ME (macular edema) as assessed from spectral-domain optical coherence tomography (SD-OCT). The presence of PDR (OR = 2.13, CI = 1.63, 2.78) and ME (OR = 2.36, CI = 1.66, 3.34) were both significantly associated with incident WESDR SN. WESDR SN was associated with incident PDR (OR = 1.53, CI = 1.09, 2.15) but not incident ME (OR = 1.31, CI = 0.92, 1.87). CONCLUSIONS: 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.

Association of Skin Intrinsic Fluorescence with Retinal Microvascular Complications of Long Term Type 1 Diabetes in the Wisconsin Epidemiologic Study of Diabetic Retinopathy.

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. 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 a 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 < 0.05) 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.