Diagnosis of diabetic peripheral neuropathy

Diagnosing diabetic peripheral neuropathy

Recognition of early signs and/or symptoms and timely intervention are crucial for preventing progression of diabetic peripheral neuropathy and complications (e.g. foot ulcerations and amputations), particularly as up to 50% of patients may be asymptomatic.^1,2

Challenges associated with diagnosis of diabetic peripheral neuropathy

Pain and other symptoms and/or signs of diabetic peripheral neuropathy significantly diminish patient quality of life, affecting physical, psychological, and social well-being.^3–6 Yet, diabetic peripheral neuropathy is frequently under- and misdiagnosed.^6,7

It can be a clinical challenge to diagnose patients with diabetic peripheral neuropathy as⁸:

Diagnostic recommendations

According to the American Academy of Clinical Endocrinology (AACE) and American Diabetes Association (ADA), diabetic peripheral neuropathy is a clinical diagnosis based on exclusion of other causes.^2,8

Screening via clinical history and physical examination is recommended to rule out nondiabetic neuropathies in all patients with diabetes^2,8:

Assessments for diabetic peripheral neuropathy should include a careful history and a combination of tests, such as^2,8,9:

According to AACE, assessments should follow the typical diabetic peripheral neuropathy pattern by starting distally and moving proximally until a sensory threshold is identified.⁸

Large-fiber function may be assessed through vibration sensation, light-touch sensation or ankle reflex testing<sup>9,10</sup><br> Small-fiber function may be evaluated with pinprick sensation and temperature discrimination tests.<sup>9,10</sup>

Large-fiber function may be assessed through vibration sensation, light-touch sensation or ankle reflex testing^9,10
Small-fiber function may be evaluated with pinprick sensation and temperature discrimination tests.^9,10

Diabetic foot exams should be performed to detect deformities and identify risks for complications such as ulceration and amputations.^2,8

Multiple other screening tools are available to aid diagnosis of diabetic peripheral neuropathy, including the Michigan Neuropathy Screening Instrument (MNSI) and the Douleur Neuropathique en 4 (DN4) questionnaire, along with other patient-reported outcome measures.¹¹

Diagnosis of atypical diabetic peripheral neuropathy

Presence of atypical symptoms may contribute to under- and misdiagnosis of diabetic peripheral neuropathy and includes^2,8:

Electrophysiological testing, skin biopsies, or referral to a neurologist may be considered when clinical features of diabetic peripheral neuropathy are atypical or when the diagnosis is unclear.^8,12

Electrophysiological testing, such as nerve conduction studies, may be used to measure large-fiber function.¹¹During nerve conduction studies, surface electrodes are used to stimulate nerves at several points of the limb and measure the response¹³
Skin biopsy of the distal leg (lower calf and ankle) to quantify intraepidermal nerve fiber density is not an appropriate screening tool due to its invasive nature but has utility as a diagnostic tool and clinical endpoint in research environments¹²

Pain and other symptoms of diabetic peripheral neuropathy may be addressed with appropriate disease management strategies and therapeutic targets. Learn more.

Symptoms

Management

Footnotes

Gandhi M et al. Drugs Context. 2022;11:2021-10-2.
Pop-Busui R et al. Diabetes Care. 2017;40:136–54.
Tesfaye S et al. J Diabetes Complications. 2023;37:108417.
Tölle T et al. J Diabetes Complications. 2006;20:26–33.
Gao Y et al. Nurs Open. 2023;10:3164–77.
Abd-Elsayed AA et al. J Pain Res. 2023;16:2269–85.
Wang W et al. Diabetes Educ. 2011;37:536–48.
Blonde L et al. Endocr Pract. 2022;28:923–1049.
Gylfadottir SS et al. J Diabetes Invest. 2019;10:1148–57.
Pop-Busui R et al. Diagnosis and treatment of painful diabetic peripheral neuropathy. Arlington (VA): American Diabetes Association; 2022. https://www.ncbi.nlm.nih.gov/books/NBK580224/. Accessed May 21, 2025.
Petropoulos IN et al. Diabetes Metab J. 2018;42:255–69.
Yang H et al. Front Endocrinol (Lausanne). 2020;10:929.
Huynh W, Kiernan MC. Aust Fam Physician. 2011;40:693–7.

N/A-05-25-0007 | June 2025