Neural dysfunction and retinopathy in persons with type 1 diabetes

ABSTRACT

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.

Conflicts of interest

None of the authors has any conflicts of interest to disclose.

Additional information

Funding

This study was supported by grant EY016379 (to B.K., R.K.) from the National Institutes of Health, Bethesda, MD. The sponsor or funding organization had no role in the design or conduct of this research.