Associations between Sensorimotor, Autonomic and Central Neuropathies in Diabetes Mellitus

Background: Patients with long-standing diabetes mellitus (DM) are exposed to hyperglycemia and metabolic disorders associated with extensive neuronal damage. Using a bedside applicable setup, the aim was to explore whether diabetes patients suffering from sensorimotor neuropathy had co-existing autonomic and central neuropathy. Methods: Twenty DM patients (10 women, average age 58.3 +/- 12.0 years) with sensorimotor polyneuropathy and 16 healthy volunteers (HV) (9 women, age 62.6 +/- 10.5 years) were recruited. Heart rate variability was recorded. Peripheral tactile detection threshold and sensation to pinprick was assessed by Von Frey-filaments. Sensitivity to pressure of the forearm extensor digitorum muscle was measured before and after conditioning pain modulation (CPM) induction by immersing the contra lateral hand into ice water in 180 seconds. Results: In comparison to HV, DM patients had lower variance (7.1 +/- 5.6 vs. 13.3 +/- 8.1 beats pr. min.; P=0.02) and mean standard deviation (3.3 +/- 2.0 vs. 5.6 +/- 2.8; P=0.01) of heart rate. They also had peripheral hypoesthesia to tactile stimulation: Median (3.0 g (0.8-12.5) vs. 1.0 g (0.4-1.4), P=0.03) and less efficacious CPM (13.9 +/- 14.8% vs. 37.4% +/- 28.9%; P=0.005). In patients, peripheral hypoesthesia was associated to mean heart rate (P=0.01), standard deviation of heart rate (P=0.004), and to CPM (P=0.046). Conclusion: DM patients with sensorimotor neuropathy showed generalized polyneuropathy evident as peripheral hypoesthesia, autonomic neuropathy and impaired CPM. Von Frey tactile detection threshold was associated with heart rate variability and CPM. The clinical approach and combined testing procedures, may serve as a prognostic platform to quantitatively evaluate the severity, extension and progression of diabetic neuropathy.