Early Detection Of Diminished Baroreflex Sensitivity In Diabetic Patients Without Evidence Of Cardiovascular Autonomic Neuropathy

Abstract

Diabetic cardiovascular autonomic neuropathy (CAN) carries an increased risk of mortality. Decreased baroreflex sensitivity (BRS) has been identified as a predictor of increased mortality following myocardial infarction. We evaluated spontaneous BRS in 39 healthy control subjects (C: age (mean ± SEM): 41.5 ± 1.9 years) and 116 diabetic patients (64% Type 1, 36% Type 2; age: 45.8 ± 1.4 years; diabetes duration: 16.9 ± 1.0 years; HbA1c: 9.2 ± 0.2%) using cross‐spectral analysis between systolic blood pressure and heart rate in the low‐frequency (LF) and high‐frequency (HF) bands as well as time domain (sequence) analysis in the supine and standing positions over 10 min. According to previously suggested definitions based on autonomic function tests (AFTs), 36 patients had definite CAN (CAN+: 3 of 7 indices abnormal), 13 had borderline CAN (CAN[+]: 2 of 7 indices abnormal), and 64 had no evidence of CAN (CAN−: 1 of 7 indices abnormal). Maximum gain in cross‐spectral LF band (standing) was significantly reduced in CAN− as compared with C (5.2 ± 0.4 vs. 7.2 ± 0.8 ms/mmHg, p < 0.05). Moreover, maximum gain in cross‐spectral HF band was significantly lower in CAN− than in C (supine: 12.0 ± 1.2 vs. 17.9 ± 2.5 ms/mmHg, p < 0.05; standing: 4.9 ± 0.5 vs. 8.7 ± 1.0 ms/mmHg, p < 0.05). The slope of the regression line between defined increases or reductions in systolic blood pressure and R‐R intervals was significantly reduced in CAN− compared to C (supine: 10.6 ± 0.7 vs. 14.2 ± 1.6 ms/mmHg, p < 0.05; standing: 5.6 ± 0.4 vs. 8.1 ± 0.7 ms/mmHg, p < 0.05). Similar differences were obtained when comparing the CAN− and CAN[+] groups, the latter showing significantly reduced BRS by both techniques (p < 0.05). In contrast, no such differences were noted when comparing the CAN[+] and CAN+ groups. In conclusion, reduced spontaneous baroreflex sensitivity is an early marker of autonomic dysfunction at a stage when autonomic function tests do not yet indicate the presence of CAN, while cases with borderline CAN show a degree of BRS abnormality that is comparable to the level seen in definite CAN. Prospective studies are needed to evaluate whether reduced BRS is a predictor of mortality in diabetic patients.