Type 2 diabetes (t2dm) remains the No. 1 cause of atraumatic limb loss in the United States. Neuropathy is a primary culprit in the process beginning with undetected foot injury that progresses to deep-seated infection and, ultimately, limb loss. Hence, it is hoped that early identification and management of diabetic peripheral neuropathy (DPN) might improve outcomes. Unfortunately, of the microvascular consequences of T2DM, neuropathy appears to be the most recalcitrant to glucose control: Glucose control appears to forestall progression of neuropathy, but not improve nerve function or reverse neuropathy.

In clinical practice, it is recommended that the diagnosis of DPN should be based on typical symptoms and physical examination (e.g., lower extremity deep tendon reflex changes). On the other hand, clinical trials usually employ sophisticated techniques such as nerve conduction testing. Comparison of tuning fork testing vs monofilament testing found the former to be the most sensitive test for identification of neuropathy. The postulated pathophysiology of DPN is uncertain and may be multifactorial, but there is some support for dysfunction of the neural microvasculature.

FDA-approved agents for DPN pain are duloxetine and pregabalin, although venlafaxine, gabapentin, carbamazepine, and alpha-lipoic acid have also demonstrated some efficacy. A recently published algorithm created by the Toronto International Neuropathy Consensus Group suggests that when traditional agents are not effective, opioid analgesia may be considered.