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Diabetic neuropathy. Need to know.

Updated: Jul 11, 2021


Definition (Sloan et al., 2018; Rosenberger et al., 2020)

Toronto Consensus Panel on Diabetic Neuropathy defined DSPN as ‘a symmetrical, length dependent sensorimotor polyneuropathy attributable to metabolic and microvessel alterations as a result of chronic hyperglycaemia exposure (DM) and cardiovascular risk covariates


"Painful diabetic neuropathy (pDN) is defned as “pain arising as a direct consequence of abnormalities in the peripheral somatosensory system in people with diabetes” (Tesfaye et al. 2010).


The two main problems are loss of sensation increasing risk of ulceration, and neuropathic pain.


Diagnostic criteria (Rosenberger et al., 2020)

pDN is diagnosed if pain lasted≥3 months has a history of confrmed dPNP and an association with abnormal sensory signs of small fber and large fber neuropathy in a neuro-anatomically plausible distal and symmetrical distribution


Presentation (Sloan et al., 2018; Rosenberger et al., 2020; Pop-Busui et al., 2017)

Symptoms are commonly aching, itching, 'sunburn like', cold pain.

Evoked pains are common by less prevalent than these other symptoms

More than half with painful-DSPN state it is severe

Commonly worse at night

These patients often also have other comorbidities

Often those with painful-DSPN develop depression and anxiety


All patients should be assessed for distal symmetric polyneuropathy starting at diagnosis of type 2 diabetes and 5 years after the diagnosis of type 1 diabetes and at least annually thereafter.


Distal symmetric neuropathy

Length dependent symmetric pattern


Diabetic amyotrophy

Syndrome of sudden severe pain in the proximal segment of a limb followed by atrophy and weakness


Diabetic mononeuropathy

Severe acute and painful often affecting cranial nerves or nerve roots. Multifocal polyneuropathy can also occur. Seem to vasculitic in nature


Epidemiology

Diabetic distal symmetrical polyneuropathy (DSPN) develops in 50% of patient with diabetes

Up to 20% develop neuropathic pain

Causes significant unemployment, mental health disorders, and physical co-morbidities


Risk factors (Sloan et al., 2018)

Increasing age

Poor glucose control

Obesity

Raised triglycerides

Smoking

Hypertension

Genetic susceptibility

More specifically for PAINFUL DSPN... Female, older, duration of diabetes, and obesity


Pathophysiology (Sloan et al., 2018)

Hyperglycaemia and hyperlipidaemia result in impaired peripheral nerve function and neuronal damage through vascular and metabolic mechanisms

Vascular issues cause local nerve hypoxia and impairment

Excess glucose activates metabolic pathways including

- Polyol pathway oxidative stress

- Protein kinase C enzyme activation leads to neurovascular impairment

- Excess tissue glucose leads to glycation end products


These processes lead to loss of myelination of small and large fibres. These lead to structural changes and axonal apoptosis in the DRG. Na channel changes have also been noted.


Examination (Rosenberger et al., 2020; Pop-Busui et al., 2017)

Clinical examination should include: inspection of the feet, evaluation of sensory loss, arterial pulses, skin state, pain assessment.

For the vast majority of patients, the diagnosis of dPNP is based on history and examination, without further necessary testing.


Distribution of both pain and sensory changes should be mapped.

Sensory changes are usually in a distal, symmetrical distribution (stocking or glove like).

Small Fiber function = Pinprick and temperature

Large-Fibre = Vibration, proprioception, monofilament and reflexes

Changes are best mapped by drawing on the skin

Decreased sense of vibration (128 Hz tuning fork), impairment of proprioception, reduced or even absent refex activity in the Achilles tendon and diminished muscle strength or atrophy of the foot muscles, which might lead to pes cavus or hammertoes


Patients frequently state that their feet feel like they are wrapped in wool or they are walking on thick socks. It is the loss of the “gift of pain” that permits patients with plantar neuropathic ulcers to walk on the lesions, inducing chronicity, frequently complicated by infection


Investigations


Management (Sloan et al., 2018; Rosenberger et al., 2020)

Multidisciplinary management is the gold standard

Only a 1/3rd will receive 50% pain relief (often with side effects and/or low satisfaction)

Good glycaemic control

Life-style modification with diet and exercise

Management of vascular risk factors and co-morbid conditions

Foot care is critically important


Pharmacological


First line: Three main drug classes: TCAs (Amitriptyline), SNRIs (Duloxetine), and Calcium channel alpha2ligands (Gabapentin and pregabalin)


Second line: Tramadol


Third and fourth line: Strong opioids, anti-convulsants, and cannabinoids


Gold nuggets (Pop-Busui et al., 2017)

Diabetic neuropathy is a diagnosis of exclusion

Up to 50% of diabetic peripheral neuropathies may be asymptomatic

If it is not recognised, significant risk for insensate feet and ulcer formation

Patients often do not report these pain symptoms to their doctors


Not every neuropathy in patients with DM is a diabetic neuropathy!

(Exclude diferential diagnosis, such as thyroid disease, autoimmune disorders, infections (e.g., HIV), vitamin defciencies (e.g., vitamin B12) or intoxications (e.g., alcohol))


References:


Kelkar, S. (2020). Diabetic Neuropathy and Clinical Practice (1st ed. 2020.). Springer Singapore. https://doi.org/10.1007/978-981-15-2417-2


Pop-Busui, R., Boulton, A. J. M., Feldman, E. L., Bril, V., Freeman, R., Malik, R. A., . . . Ziegler, D. (2017). Diabetic Neuropathy: A Position Statement by the American Diabetes Association. Diabetes Care, 40(1), 136-154. doi:10.2337/dc16-2042


Rosenberger, D. C., Blechschmidt, V., Timmerman, H., Wolff, A., & Treede, R. D. (2020). Challenges of neuropathic pain: focus on diabetic neuropathy. Journal of Neural Transmission, 1-36.


Sloan, G., Shillo, P., Selvarajah, D., Wu, J., Wilkinson, I. D., Tracey, I., ... & Tesfaye, S. (2018). A new look at painful diabetic neuropathy. Diabetes research and clinical practice, 144, 177-191.

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