Cardiac autonomic nerve dysfunction predicts incident retinopathy and early kidney dysfunction in adolescents with type 1 diabetes

Objective:

Cardiac autonomic nerve dysfunction (CAN) may contribute to vascular complications in diabetes. We hypothesized that adolescents with CAN are at greater risk of DR and early kidney dysfunction.

Research Design and Methods:

This is a prospective longitudinal study of 725 adolescents with type 1 diabetes without retinopathy and albuminuria at baseline. Early CAN was defined as >1 abnormality of 7 heart rate tests derived from a 10-minute ECG recording using Labchart Pro; retinopathy as the presence of >1 microaneurysm, early kidney dysfunction as albumin excretion rate (AER) >7.5 mcg/min and albuminuria as AER >20 mcg/min. Multivariable generalized estimating equations (GEE) were utilized to examine the association between CAN and retinopathy or early kidney dysfunction (Odds ratio with 95% confidence intervals (CI)).Cox- regression analysis assessed cumulative risks of incident retinopathy and albuminuria (hazard ratio with 95% CI).

Results:

At baseline mean age was 13.6±2.6 years, 52% male, mean diabetes duration 6.1±3.3 years. Over a median follow-up of 3.8 [interquartile range 2.2-7.5] years, complications rates were retinopathy at 27%, early kidney dysfunction at 16%, albuminuria at 3%, mean study HbA1c was 72.3 ± 16 mmol/mmol (8.6 ±1.4%). Cardiac autonomic nerve dysfunction predicted incident retinopathy: OR 2.0 (CI: 1.4, 2.9) and early kidney dysfunction 1.4 (1.0, 2.0) after adjusting for HbA1C and duration. Cardiac autonomic nerve dysfunction predicted retinopathy: HR 1.57 (CI 1.09, 2.26) and albuminuria 2.30 (CI; 1.05, 5.04) independently of HbA1c.

Conclusions:

CAN predicted incident retinopathy and kidney dysfunction in adolescents with type 1 diabetes, likely reflecting autonomic microvascular dysregulation contributing to complications. Therefore, screening and interventions to reduce CAN may influence complications risk.