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To validate nerve-axon reflex-related vasodilatation as an objective method to evaluate C-nociceptive fibre function by comparing it with the standard diagnostic criteria.Neuropathy was evaluated in 41 patients with diabetes (26 men and 15 women) without peripheral vascular disease by assessing the Neuropathy Symptom Score, the Neuropathy Disability Score (NDS), the vibration perception threshold (VPT), the heat detection threshold (HDT), nerve conduction parameters and standard cardiovascular tests. The neurovascular response to 1% acetylcholine (Ach) iontophoresis was measured at the forearm and at both feet by laser flowmetry. An age-matched and sex-matched control group of 10 healthy people was also included.Significant correlations were observed between the neurovascular response at the foot and HDT (r(s) = -0.658; p0.0001), NDS (r(s) = -0.665; p0.0001), VPT (r(s) = -0.548; p = 0.0005), tibial nerve conduction velocity (r(s) = 0.631; p = 0.0002), sural nerve amplitude (r(s) = 0.581; p = 0.0002) and autonomic function tests. According to the NDS, in patients with diabetes who had mild, moderate or severe neuropathy, a significantly lower neurovascular response was seen at the foot than in patients without neuropathy and controls. A neurovascular response50% was found to be highly sensitive (90%), with a good specificity (74%), in identifying patients with diabetic neuropathy.Small-fibre dysfunction can be diagnosed reliably with neurovascular response assessment. This response is already reduced in the early stages of peripheral neuropathy, supporting the hypothesis that small-fibre impairment is an early event in the natural history of diabetic neuropathy.

Objective: To assess the frequency of additional causes of distal sensory polyneuropathy (DSP) in patients with diabetes mellitus (DM). Methods: Retrospective review of patients with DM and DSP during a 5 year period. A quantitative sensory score (QSS) was determined at the initial evaluation and extensive laboratory and EMG studies were performed. Patients with one or more potential causes for DSP were compared to those with DM alone. Results: Fifty five patients (53%) had potential additional causes for DSP. These included: neurotoxic medications (seven), alcohol abuse (six), and B12 deficiency and renal disease (four each). The most common laboratory abnormalities were: abnormally low levels of vitamin B6 (11) or B1 (10), monoclonal gammopathy (eight), and hypertriglyceridaemia (eight). Twenty six (25%) subjects had more than one additional cause. Nine (9%) had three or more demyelinating features on EMG. There was a trend toward a lower QSS score (p = 0.05) and reduced mean amplitude of the sensory potentials in those with additional causes. Those with additional causes more often had upper limb sensory symptoms (p = 0.001) and sensory findings (p = 0.003). Conclusion: There was a high frequency of additional sources of DSP in patients with DM. These patients more often had sensory symptoms and findings in the hands. Tests that may be useful in the evaluation of DSP in diabetic patients include measures of vitamins B1, B6, B12, serum triglycerides, and immunofixation.

Background: A large number of nondigitized electrocardiograph (ECG) strips are routinely collected in larger cohort studies such as the ADDITION study (Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care). These ECG strips are routinely read manually but may contain overlooked information revealing cardiac autonomic dysfunction. The aim of this study was to investigate whether clinical information may be lost using manual R wave to R wave (RR) interval measurements in the calculation of heart rate variability (HRV) in patients with type 2 diabetes mellitus (T2DM). Method: From the Danish part of the ADDITION study, we randomly selected 120 T2DM patients at baseline of the ADDITION study. Analysis of the ECG strips was performed using two different methods: (1) by experienced technicians using rulers and (2) by experienced technicians using a high-resolution computer-assisted method. Calculation of heart rate and time domain HRV [standard deviation of normal-to-normal RR intervals (SDNN) and root mean square of successive differences (RMSSD)] were performed with the same software. Results: When comparing results from the two methods, the following values of Pearson's r are obtained: 0.98 for heart rate, 0.76 for SDNN, and 0.68 for RMSSD. These results indicate that heart rate and HRV measurements by the computer-assisted and manually based methods correlate. However, Bland-Altman plots and Pitman's test of difference in variance revealed poor agreements ( p < .01) for both HRV measurements (SDNN and RMSSD); only heart rate showed substantiated agreement ( p = .54) between the two methods. Low HRV was statistically significantly associated to high heart rate, systolic blood pressure, and diastolic blood pressure in these screen-detected T2DM patients. Conclusions: Paper ECG strips may contain overlooked clinical information on the status of autonomic function in patients with T2DM. In our study, manual measurements of RR intervals were inferior to the computer-assisted method. Based on this study, we recommend cautiousness in the clinical use and interpretation of HRV based on manual or low resolution measurements of RR intervals from ECG strips. High resolution measurements of RR intervals reveal significant associations between low HRV and high heart rate, systolic blood pressure, and diastolic blood pressure among patients with screen-detected T2DM. It is feasible to use a computer-assisted method to determine RR intervals in patients with T2DM.

To determine risk factors for sudden cardiac death and the role of diabetic autonomic neuropathy (DAN) in the Rochester diabetic neuropathy study (RDNS).Associations between diabetic and cardiovascular complications, including DAN, and the risk of sudden cardiac death were studied among 462 diabetic patients (151 type 1) enrolled in the RDNS. Medical records, death certificates, and necropsy reports were assessed for causes of sudden cardiac death.21 cases of sudden cardiac death were identified over 15 years of follow up. In bivariate analysis of risk covariates, the following were significant: ECG 1 (evolving and previous myocardial infarctions): hazard ratio (HR) = 4.4 (95% confidence interval (CI), 1.6 to 12.1), p = 0.004; ECG 2 (bundle branch block or pacing): HR = 8.6 (2.9 to 25.4), p0.001; ECG 1 or ECG 2: HR = 4.2 (1.3 to 13.4), p = 0.014; and nephropathy stage: HR = 2.1 (1.3 to 3.4), p = 0.002. Adjusting for ECG 1 or ECG 2, autonomic scores, QTc interval, high density lipoprotein (HDL) cholesterol, 24 hour microalbuminuria, and 24 hour total proteinuria were significant. However, adjusting for nephropathy, none of the autonomic indices, QTc interval, HDL cholesterol, microalbuminuria, or total proteinuria was significant. At necropsy, all patients with sudden cardiac death had coronary artery or myocardial disease.Sudden cardiac death was correlated with atherosclerotic heart disease and nephropathy, and to a lesser degree with DAN and HDL cholesterol. Although DAN is associated with sudden cardiac death, it is unlikely to be its primary cause.

To investigate the potential benefits from lightly touching an external supporting device on automatic postural responses to support surface translations, in subjects with profound sensory neuropathy in the feet due to diabetes mellitus (DM-PN).Eight subjects with DM-PN and 10 age matched controls were tested under randomly ordered conditions of no fingertip touch (NT), light touch (LT;1 N), and heavy touch (HT, as needed) of a stationary touch plate, during three backward translation velocities of the support surface at 10, 20, and 30 cm/s. Dependent variables included response latencies, CoP velocity, and the slope of the relation between centre of pressure (CoP) velocity and translation velocity as a measure of response scaling.Postural response latencies were significantly longer and scaling of initial response magnitude in proportion to translation velocity was significantly smaller in the DM-PN subjects compared to the control subjects. LT had no significant effect on response latencies of the DM-PN patients. Fingertip touch increased the slope of the scaling of postural response magnitude in both groups. However, DM-PN subjects had to use HT to improve response scaling, whereas control subjects improved scaling with LT as well as HT. LT significantly increased rightward CoP velocity towards the touch plate in all subjects.LT did not reduce the latency or improve the scaling of automatic postural responses in subjects with peripheral neuropathy. The major effect of LT on the automatic postural responses of the DM-PN subjects was in increasing CoP velocity towards the side of the supporting device. HT in neuropathy subjects and LT in age matched control subjects increased the sensitivity of initial postural response scaling, suggesting that somatosensory substitution from a cane in the hand could be used to improve the magnitude of medium latency postural responses to slips and trips.