Abstract
OBJECTIVE: Reduced heart rate variability (HRV) is classically viewed as an early phenomenon in diabetic sensorimotor polyneuropathy (DSP). We aimed to determine the characteristics of HRV across the spectrum of clinical DSP in type 1 diabetes. RESEARCH DESIGN AND METHODS: Eighty-nine diabetic subjects and 60 healthy volunteers underwent assessment of RR interval variation (RR(var)) during deep breathing and clinical and electrophysiological examination. We examined the distribution of age-standardized RR(var) across the spectrum of clinical DSP, identified variables associated with RR(var) in multivariate regression, and compared RR(var) with validated measures of neuropathy. RESULTS: Age-standardized RR(var) had a significant, step-wise, inverse relationship with ordinal categories of increasing DSP severity (β = -5.4, P < 0.0001) among subjects with diabetes. Case subjects with DSP had substantially lower age-standardized RR(var) compared with diabetic control subjects without DSP (β = -5.2, P < 0.01), although there was substantial overlap of RR(var) between diabetic case subjects and control subjects and the healthy volunteer cohort. In multivariate analysis, advanced age was independently associated with lower RR(var) in both healthy volunteers and diabetic subjects, whereas higher glycated hemoglobin A(1c) and systolic blood pressure were independently associated with lower RR(var) in diabetic subjects. RR(var) had a significant association with validated measures of large and small fiber neuropathy. CONCLUSIONS: HRV may be a biomarker for clinical DSP and is associated cross-sectionally with both early and late measures of neuropathy. The low HRV observed in some control subjects without DSP and in most case subjects with severe DSP may signify that HRV has different prognostic implications in these groups, requiring further longitudinal study.