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Cardiac autonomic function in relation to diabetic retinopathy development and progression in type 1 diabetic patients: a prospective observational study

Denervation of the cardiovascular system is one of the earliest manifestations of diabetic autonomic neuropathy (DAN). Various studies have shown that it is strongly associated with microvascular complications of diabetes, microalbuminuria and diabetic retinopathy (DR). In this longitudinal observational study we aimed to determine whether cardiac autonomic fuction contributes to risk of DR development and progression in normoalbuminuric type 1 diabetic (T1DM) without syptomiatic DAN . One hundred fifty four normoalbuminuric T1DM patients were included in the study. Urine albumin excretion (UAE) was measured from two 24-h urine samples and determined as the mean of 24-h urine collections to minimize variability. Photodocumented retinopathy status was made according to EURODIAB protocol. Normoalbuminuria was defined as a UAE<30 mg/24h. The battery of cardiovascular autonomic function (AFT) tests included: heart rate variation at rest (HRV-CV), HRV-CV during deep breathing (dbHRV-CV), Valsalva manoeuvre and active orthostatic test and blood pressure response to standing. In the frequency domain we measured high-frequency power (HF), and low frequency power (LF) using a fast Fourier transformation in order to calculate the power spectral density curve. Participants were reexamined after 18 months to update their glycaemic control, UAE and retinopathy status. Patients with NPDR showed significantly lower HRV at rest, HRV during deep breathing as well as deep breathing E/I ratio compared to group of patients without DR. There was a significant attenuation for both LF and HF Power in the NPDR group. In- between groups diabetes duration was significantly different although long-term glycaemic control assessed by glycated haemoglobin A1c (HbA1c) was similar. Six (3.89%) patients developed albuminuria during 18 months follow up period while 21 (13.36%) developed NPDR or progressed from NPDR to PDR. A Cox regression model adjusted for age, gender, disease duration, HbA1c, hypertension prevalence, ACE inhibitor use and smoking status showed that higher HRV-CV, dbHRV-CV as well as LF Power reduce the risk of DR incidence and progression (HR 0.664 (0.514 to 0.866), p=0.002 ; 0.873 (0.784 to 0.972), p=0.013 and 0.909 (0.892 to 0.964), p=0.014, resepectively). In this prospective, longitudinal, observational cohort study, we demonstrated that AFT results might serve as an independent prognostic factor for the future development or progression of DR in T1DM patients even in the DAN absence.

cardiac autonomic dysfunction ; type 1 diabetes ; retinopathy

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