Fig. 1Bedside neurological and sensory nerve testing. (A) Vibration. Patients are notified when they cannot feel the vibrations from a 128-Hz tuning fork (first interphalangeal joint of the great toe) when the toes are extended, and the investigator feels the vibration and measures the time when the feeling disappeared. A time difference ≥10 seconds between the investigator and the patient is considered abnormal [33]. (B) Pressure: 10-g monofilaments are pressed on 10 points on the sole and dorsum of the feet until the monofilament begins to bend (100 mN). If the patient has sensation in fewer than seven points, the results is considered abnormal [33]. Four sites per foot, such as the hallux and metatarsal heads 1, 3, and 5, should be screened [4]. (C) Noxious stimuli and (D) light touch. The patient is touched on the foot using a sterile pin, toothpick, and cotton wisp and asked to identify a "sharp or dull" or "light touch" with their eyes closed [33]. (E) Warm/cold. Tip-therm (temperature discriminator; AXON GmbH) is a pen-like device with a plastic cylinder on one end and a metal cylinder on the other end, which is applied to the dorsum of each foot at irregular intervals so patients can identify the sensation as cold or not with their eyes closed [32]. (F) Sudomotor function. Indicator tests (Neuropad, miro Verbandstoffe) are applied to both soles at the level of the first and second metatarsal heads. The time to color change from blue to pink is more than 10 seconds; the result is considered abnormal [34].
Fig. 2Definition and severity assessment of diabetic peripheral neuropathy (DPN) proposed by the Toronto Diabetic Neuropathy Expert Group. Numbers in each column refer to the definitions of the minimal criteria for DPN, and the number in parentheses is the stage of severity: 1 ("possible"), 2 ("probable"), or 3 ("confirmed") for clinical practice and 3 or 4 ("subclinical") for research studies [6]. Severity is staged based on the symptoms, signs, and nerve conduction (NC) abnormalities: stage 0, no NC abnormality; 1a, subclinical but without symptoms or signs; 1b, subclinical with signs but no symptoms; 2a, subclinical with symptoms regardless of signs; and 2b (not shown here), subclinical with unequivocal weakness of ankle dorsiflexion [5].
Fig. 3Diagnostic approach to diabetic peripheral neuropathy (DPN) proposed by the Korean Diabetes Association [7].
Table 1Peripheral Nerve Fibers and Function
Classification (diameter) [8] |
Function |
Clinical sign and sensory testing |
Myelinated Aα (13–20 μm) |
Motor |
Decreased ankle and knee reflexes |
Thickly myelinated Aβ (6–12 μm) |
Proprioception |
Impaired proprioception |
Vibration |
Decreased vibration sense (128-Hz tuning fork) |
Pressure |
Hyperalgesia (cotton swab), hypoesthesia (10-g SWMF) |
Thinly myelinated Aδ fiber (1–5 μm) |
Cold |
Hyperalgesia, hypoesthesia, hypoalgesia (Tip-therm, AXON GmbH) |
Sharp pain |
Allodynia, hyperalgesia (cotton swab), hypoesthesia (10-g SWMF), hypoalgesia (pin-prick) |
Unmyelinated C fibers (0.2–1.5 μm) |
Warmth |
Hyperalgesia, hypoesthesia, hypoalgesia (Tip-therm) |
Burning pain |
Hyperalgesia (cotton swab), hypoesthesia (10-g SWMF), hypoalgesia (pin-prick) |
Autonomic function |
Decreased sweating |
Table 2Methods of Sensorimotor Neural Test for Diagnosis of Diabetic Peripheral Neuropathy
Scoring system |
Items |
Description |
Michigan neuropathy screening instrument [28] |
A 15-item self-administered questionnaire: pain, temperature sensation, tingling, numbness, sensory symptoms, cramps and muscle weakness, foots ulcers or cracks and amputation. |
Abnormal, if ≥3 response |
Michigan diabetic neuropathy score [28] |
Appearance of feet |
0, normal; 1, abnormal |
Ulceration |
0, normal; 1, abnormal |
Ankle reflexes |
0, present; 0.5, reduced; 1, absent |
Vibration perception |
0, present; 0.5, reduced; 1, absent |
Abnormal, if ≥2/4 score |
Revised neuropathy disability score [23] |
Vibration sensation (128-Hz tuning fork) |
0, present; 1, reduced/absent |
Temperature sensation |
0, present; 1, reduced/absent |
Pin-prick |
0, present; 1, reduced/absent |
Ankle reflex |
0, normal; 1, reduced; 2, absent |
Abnormal, if ≥6/10 points |