Diabetic Neuropathy Workup and Treatment
The recommended workup for diabetic neuropathy includes annual screening with small and large fiber function tests, while treatment should focus on optimizing glucose control and using first-line medications such as pregabalin, duloxetine, or gabapentin for painful symptoms.
Diagnostic Workup
Screening Recommendations
- All patients with type 2 diabetes should be assessed for diabetic peripheral neuropathy (DPN) at diagnosis, while those with type 1 diabetes should be assessed 5 years after diagnosis, with annual evaluations thereafter 1, 2
- Up to 50% of DPN cases are asymptomatic but still increase risk for foot ulceration and amputation, highlighting the importance of systematic screening 2
Clinical Assessment
- Small-fiber function assessment: pinprick and temperature sensation tests 1
- Large-fiber function assessment: vibration perception using a 128-Hz tuning fork 1
- Protective sensation assessment: 10-g monofilament testing to identify feet at risk for ulceration 1
Exclusion of Other Causes
- DPN is a diagnosis of exclusion; other causes must be ruled out, including: 1, 2
- Toxins (e.g., alcohol)
- Neurotoxic medications (e.g., chemotherapy)
- Vitamin B12 deficiency
- Hypothyroidism
- Renal disease
- Malignancies (e.g., multiple myeloma, bronchogenic carcinoma)
- Infections (e.g., HIV)
- Chronic inflammatory demyelinating neuropathy
- Inherited neuropathies
- Vasculitis
Additional Testing
- Electrophysiological testing or referral to a neurologist is rarely needed, except when clinical features are atypical or the diagnosis is unclear 1
- Assessment for autonomic neuropathy symptoms should be conducted in patients with microvascular complications 1
Treatment Approach
Glycemic Control
- Optimize glucose control to prevent or delay the development of neuropathy in patients with type 1 diabetes and to slow the progression in patients with type 2 diabetes 1
- Near-normal glycemic control implemented early is most effective for prevention, especially in type 1 diabetes 2, 3
Pharmacological Treatment for Painful DPN
First-Line Medications
- Pregabalin: Start at 50 mg three times a day (150 mg/day), may increase to 100 mg three times a day (300 mg/day) within 1 week based on efficacy and tolerability 4
- Duloxetine: 60 mg once daily 1, 2
- Gabapentin: 300-1,200 mg three times daily 2, 5
Alternative Options
- Tricyclic antidepressants (e.g., amitriptyline, nortriptyline) 1, 2
- Serotonin norepinephrine reuptake inhibitors (e.g., venlafaxine) 2, 3
- Sodium channel blockers (e.g., carbamazepine, lamotrigine) 2, 6
- Topical agents: capsaicin (8% patch or 0.075% cream) 2, 7
Management of Autonomic Neuropathy
- Cardiac autonomic neuropathy: Monitor for resting tachycardia and orthostatic hypotension 1
- Gastrointestinal neuropathies: Evaluate for gastroparesis, constipation, diarrhea 1, 3
- Genitourinary dysfunction: Assess for erectile dysfunction, neurogenic bladder 3, 5
Common Pitfalls and Caveats
- Adverse events from medications may be more severe in older patients; consider lower starting doses and slower titration 2, 5
- Opioids should generally be avoided for chronic neuropathic pain due to risk of addiction 2, 7
- Although pregabalin was studied at 600 mg/day, there is no evidence that this dose provides additional significant benefit, and it was less well tolerated 4
- Duloxetine may cause a small increase in A1C in longer-term studies 2
- Regular foot examinations are critical to prevent complications; all patients with DPN should have annual 10-g monofilament testing 1, 2
- Patient education about foot care is essential to prevent ulceration and amputation 2, 7