Diabetic neuropathy represents one of the most frequent microvascular complications of diabetes, both in type 1 (T1DM) and type 2 diabetes mellitus (T2DM) and can involve the peripheral nervous system and the autonomic nervous system.1,2 Peripheral neuropathy may affect around 20 % and up to 50 % of patients living with diabetes.3, 4, 5, 6, 7

The diabetic peripheral neuropathy or polyneuropathy (DPN) is the most common form of diabetic neuropathy. DPN includes sensory or sensory-motor, painful and vegetative, symmetrical or focal forms, and consists in a damage to the peripheral fibers which innervate upper and lower limbs.1,7 Up to 50 % of diabetic peripheral neuropathies may be asymptomatic.7 DPN is associated with morbidities including disabling pain and risk of foot ulceration and amputations.

Diabetic autonomic neuropathy may affect many organs. The heart, through the vagus nerve and later the sympathetic nervous system, is particularly sensitive to neuropathic damage. Cardiac autonomic neuropathy (CAN) may account for various symptoms and signs.7,8 However, CAN is more often asymptomatic. Silent CAN may be detected in around 20 % of patients with diabetes and by the early stages of diabetes continuum including prediabetes.9, 10, 11 CAN, even silent, is associated with a poor cardiovascular prognosis.8,12

Thus, early identification of patients with DPN and CAN using non-invasive methods is critical in order to prevent the progression of neuropathy and reduce the risks related to these complications.

Various tools may be used to screen and diagnose patients for DPN. The clinical portion of the Michigan Neuropathy Screening Instrument (MNSI) based on a lower extremity examination that includes feet inspection and assessment of vibratory sensitivity, monofilament perception and ankle reflexes is a simple one, and MNSI with a score ≥ 2.5 was shown to be a good screening tool for diabetic neuropathy.13,14 Sensory deficits and altered thresholds for sensory stimuli can be measured reliably using quantitative sensory testing (QST). Several international expert consensus have endorsed QST assessment for the quantification of sensory deficits.1,15, 16, 17 NerveCheck Master (NCKM) is a portable device to perform tests to screen peripheral sensory neuropathy. By assessing vibration (VPT), warm (WPT), cold (CPT) and heat pain (HPT) perception thresholds, NCKM allows to detect the presence of both small and large fibers damage.18 This tool was shown to offer good reproducibility and comparable diagnostic accuracy to established QST devices for the diagnosis of DPN.19 NCKM was also considered to offer good diagnostic utility for identifying sensory deficits, compared to established tests of large and small fiber neuropathy, based on nerve conduction study and intraepidermal and corneal nerve fiber density, respectively.18

Regarding CAN, silent CAN may be detected using various methods, in particular standard cardiac autonomic function tests.8 CAN is underdiagnosed mostly because these tests are time-consuming and not commonly performed despite being recommended.20

The association between CAN and DPN is still a matter of debate. However, some papers have reported an association between small fiber neuropathy, which affects peripheral thin myelinated Aδ-fibers and unmyelinated C-fibers, and CAN.21 Small fibers serve nociceptive and autonomic function, and their impairment may result in sensory and autonomic abnormalities, including orthostatic hypotension and cardiac autonomic dysfunction.22

The aim of the present study was to assess the role of NCKM against MNSI to screen patients with T1DM or T2DM for both peripheral and cardiac autonomic neuropathy.