Painful diabetic neuropathy

Diabetes mellitus is one of the most common chronic medical conditions;

• up to 50% may develop diabetic polyneuropathy (1)
• the incidence is linked to the duration of diabetes
• one meta-analysis found that individuals with type 2 diabetes had a higher prevalence of neuropathy (31.5%) than those with type 1 diabetes (17.5%) (2)
• patients with peripheral neuropathy often present with varying degrees of numbness, tingling, aching, burning sensation, weakness of limbs, hyperalgesia, allodynia, and pain. This pain has been characterized as superficial, deep-seated, or severe, unremitting pain with exacerbation at night. (3)

Pathophysiology (1):

• the pathogenesis of painful symptoms remains unclear but is known to be a complex consequence of hyperglycaemia-induced alterations in multiple biochemical pathways, and is associated with other metabolic and vascular factors.
• the Epidemiology of Diabetes Interventions and Complications (EDIC) study supported a close association between the severity and/or duration of hyperglycaemia and the development and progression of neuropathy (4)
• the Diabetes Control and Complications Trial (DCCT) provided strong evidence for the importance of hyperglycaemia, insulin-deficiency, or both in the pathogenesis of DN in type 1 diabetes and a reduced incidence of diabetic neuropathy in the intensive glycaemic control treatment group (5)
• cardiovascular risk factors such as hypertension and elevated serum triglycerides are each independently associated with development of diabetic neuropathy (6)

Clinical features

• symptoms of painful diabetic neuropathy include burning pains, pins and needles, shooting pains down the legs, increased touch sensation (hyperaesthesia), and even numbness (1)

Diagnosis: (1)

• measurement of clinical pain is difficult because it can be influenced by the individual personality, past experiences and other psychological variables. Therefore pain assessment has to rely on subjective evaluation
• the presentation of diabetic neuropathy is variable. Up to 50% of patients may be completely asymptomatic. (7)
• a lower extremity neurological physical exam should include muscle strength, reflex, and sensation evaluation, including light touch with a monofilament, vibratory sensation, and proprioception. A dermatological exam demonstrating dry/cracked skin may point to autonomic neuropathy, while pedal deformities (eg, hammertoes) suggest motor neuropathy. (8)

Reference:

1. Iqbal Z, Azmi S, Yadav R, et al. Diabetic peripheral neuropathy: epidemiology, diagnosis, and pharmacotherapy. Clin Ther. 2018 Apr 30;40(6):828-49.
2. Sun J, Wang Y, Zhang X, et al. Prevalence of peripheral neuropathy in patients with diabetes: a systematic review and meta-analysis. Prim Care Diabetes. 2020 Oct;14(5):435-44.
3. Çakici N et al. Systematic review of treatments for diabetic peripheral neuropathy. Diabet Med. 2016 Nov;33(11):1466-1476.
4. Martin CL, Albers J, Herman WH, et al. Neuropathy among the diabetes control and complications trial cohort 8 years after trial completion. Diabetes Care. 2006 Feb;29(2):340-4.
5. Nathan DM, Genuth S, Lachin J, et al; Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993 Sep 30;329(14):977-86.
6. Tesfaye S, Chaturvedi N, Eaton SE, et al; EURODIAB Prospective Complications Study Group. Vascular risk factors and diabetic neuropathy. N Engl J Med. 2005 Jan 27;352(4):341-50.
7. Pop-Busui R, Boulton AJ, Feldman EL, et al. Diabetic neuropathy: a position statement by the American Diabetes Association. Diabetes Care. 2017 Jan;40(1):136-54.
8. Sloan G, Selvarajah D, Tesfaye S. Pathogenesis, diagnosis and clinical management of diabetic sensorimotor peripheral neuropathy. Nat Rev Endocrinol. 2021 Jul;17(7):400-420.