The SAS was designed to assess autonomic symptoms in subjects with neuropathy and was found to have a slightly greater sensitivity and specificity in subjects with early diabetic neuropathy than the ASP. The questions in the SAS were designed to improve subject understanding and to reduce uncertainty in the responses. Currently available autonomic questionnaires are lengthy, complex, and take training and considerable time to score. In contrast, the SAS can be rapidly completed and scored. Furthermore, interpretation of the SAS is not dependent on age, gender, body mass index, and other factors. This provides for a flexible and more universally acceptable scale to assess autonomic function in subjects with neuropathy. However, further validation of the SAS is needed in blinded and longitudinal clinical studies.
There was a difference in both the SAS symptom score and the TIS between control and neuropathy subjects. This indicates that the SAS has power to distinguish between control subjects and those with peripheral neuropathy. The SAS symptom score and TIS are not affected by age, gender, body mass index, weight, or height. This indicates that the SAS would perform well across subject groups in a clinical trial or epidemiologic study and would be less likely to be affected by common confounding variables. The SAS demonstrated a strong association with the ASP total score and for the ASP domains of secretomotor, vasomotor, and orthostatic intolerance. This is consistent with the observation that symptoms that tested these 3 autonomic domains were most commonly reported by subjects with neuropathy and also showed the greatest internal consistency. Furthermore, both the SAS symptom score and TIS showed no association between the SAS and the ASP domains of gastrointestinal dysfunction and gastrointestinal symptoms showed the lowest internal consistency. These results may be explained by the fact that this study examined subjects with IGR and early diabetic neuropathy. Although patients with type 2 diabetes commonly have autonomic symptoms, the symptoms are usually mild and in one study the syncope and gastrointestinal symptom domains on the ASP did not differ from control subjects.3
The SAS was further validated by an association between an increased SAS symptom score or TIS and a reduced forearm or foot sweat volume on QSART or a reduced 30:15 ratio. However, there was no association seen between the SAS symptom score or TIS and the E:I ratio, HRR, Valsalva ratio, abnormal tilt table response, CASS total score, or CASS subscores. These findings are consistent with a previous study that found only a weak association between autonomic symptom scores on the ASP and autonomic deficits on the CASS in patients with diabetes.3
Only a few subjects were taking a medication with significant anticholinergic properties that may reduce sweating, and these were discontinued for at least 24 hours prior to performing the QSART.19
Thus, these medications would not significantly affect the results in this study. These previous studies highlight the need to examine autonomic symptoms independently of autonomic deficits. The present study raises the possibility that early diabetic neuropathy is associated with a mild autonomic neuropathy that current autonomic tests are not sensitive enough to detect or that autonomic symptom scores overrate for the presence of autonomic neuropathy.
Compared to controls, subjects with IGR have been shown to have greater abnormalities in most cardiovascular reflex tests and greater heart rate variability characterized by the triangle index.8
In contrast, another study examined patients with newly diagnosed IGT with a battery of autonomic tests including heart rate variation variability, heart rate response to deep breathing, heart rate response to Valsalva maneuver, blood pressure response to standing up quickly, and skin sympathetic skin response (SSR) that evaluates postganglionic sympathetic sudomotor function but is less precise than the QSART.7
They found no difference compared to controls in measures of CAN. However, they did find lower amplitudes of the SSR in the IGT group compared to healthy controls that is consistent with the presence of a sudomotor autonomic neuropathy. The importance of abnormal sudomotor responses in subjects with IGR was also confirmed in other studies.2,6
This finding indicates that sudomotor fibers tend to be affected earlier in autonomic neuropathy in patients with IGR and that CAN may develop at a later stage or may require more sensitive tests to detect it than tests commonly used in the clinic.
In future studies the SAS could be adjusted to exclude the questions that individually were less reliable; however, excluding these questions would not affect the overall reliability of the test. A potential weakness of the study is the difference in the mean age of control men vs control women and individuals with neuropathy. This may be because it can be difficult to find age-matched male controls who have a normal neurologic examination, have no evidence of peripheral autonomic neuropathy, and are not on any medications that may even mildly affect autonomic functioning. However, despite the younger age of the control men, this had no affect on the validity of the study because there was no difference between age for the SAS symptom score or TIS in either control or neuropathy subjects. Future studies should address performance of the SAS in larger more diverse populations of subjects and in groups of subjects with other types of neuropathy. Despite these caveats, a validated questionnaire such as the SAS that is sensitive enough to detect mild autonomic neuropathy, is simple to complete, and performs consistently in subjects could potentially aid in the early detection and diagnosis of diabetic autonomic neuropathy.