R-R variation and the Valsalva ratio are commonly used to quantitatively assess diabetic autonomic neuropathy (DAN). To assess the sensitivity of these two measures to parasympathetic ablation, 12 nondiabetic subjects were tested before and after graded doses (0.3–4.0 mg i.v.) of atropine. R-R variation was significantly reduced at 0.7 mg, whereas Valsalva ratio was not significantly smaller until the 2.0-mg dose of atropine. R-R variation continued to become progressively smaller during the 0.85-, 1.0-, and 2.0-mg doses. Valsalva ratio, but not R-R variation, was further reduced by the 4.0- mg dose. To further compare these two measures, two groups of diabetic subjects were compared with a group of nondiabetic subjects (n = 22). One group of diabetic subjects had symptoms of DAN (n = 22), and the other diabetic group had no symptoms of DAN (n = 19). In DAN subjects, both R-R variation (nondiabetic 33.2 ± 4.3 vs. DAN 9.8 ± 1.2, P < .001) and the Valsalva ratio (nondiabetic 1.98 ± 0.07 vs. DAN 1.55 ± 0.07, P < .001) were reduced. However, in asymptomatic subjects, R-R variation (23.2 ± 3.9, P < .05), but not Valsalva ratio (1.94 ± 0.13, NS), was less than nondiabetic subjects. Even after p-blockade, R-R variation was still less in both groups of diabetic subjects (nondiabetic 34.4 ± 4.2 vs. DAN 7.4 ± 1.3, P < .001; asymptomatic 21.8 ± 3.3, P < .02). Thus, the reduced R-R variation is more likely due to decreased parasympathetic rather than increased sympathetic activity. We conclude that R-R variation is more sensitive than Valsalva ratio in detecting parasympathetic ablation and is useful for early detection and follow-up of mild autonomic dysfunction. Valsalva ratio may be more useful for sequential long-term evaluation in subjects with severe diabetic autonomic dysfunction, in whom R-R variation is maximally suppressed.

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