Diagnostic Steps and Management Recommendations for Diabetic Neuropathy

Type of NeuropathySymptomsClinical SignsDiagnosisManagement Recommendations
DSPNBurning painTests for small-fiber unction:Assess symptoms (history taking)Prevention
Lancinating or shooting painPinprick (push pin)Assess clinical signsGlucose control targeting near-normal glycemia: strong evidence for type 1 diabetes; modest data for type 2 diabetes
Paresthesias (tingling and prickling sensation)Temperature sensation discriminationConfirm pattern for symptoms and signs:Lifestyle modifications: emerging as effective treatment strategies in patients with IGT/metabolic syndrome or type 2 diabetes
Hyperalgesia (exaggerated response to painful stimuli)Tests for large-fiber function:Distal-to-proximal (stocking-glove)Prevention of foot complications
Allodynia (pain evoked by light touch)Vibration perception (128-Hz tuning fork)SymmetricalPain treatment (see Figure 1)
Note. Neuropathic pain may be the first symptom that prompts patients to seek medical care.ProprioceptionCombine at least two of the small- and large-fiber tests listed in the previous column (e.g., pinprick plus vibration) for higher sensitivity and specificityAnticonvulsants:
Light touch to 10-g monofilament (on dorsal aspect of the great toe bilaterally)Differential (as applicable):Pregabalin* 150–600 mg/day
Ankle reflexesFamily/medication historyGabapentin 1,800–3,600 mg/day
Serum B12Monoamine reuptake inhibitors:
Folic acid• Selective norepinephrine-serotonin reuptake inhibitors
Thyroid functionDuloxetine* 60–120 mg/day
Complete blood countVenlafaxine 150–225 mg/day
Metabolic panelTricyclic antidepressants
Serum protein immunoelectrophoresisAmitriptyline 25–100 mg/day (with titration)
Note. Electrophysiological testing or referral to a neurologist is rarely needed in clinical practice except for situations in which clinical features are atypical and a different etiology is suspected (i.e., motor greater than sensory neuropathy, asymmetry of symptoms and signs, or rapid progression).Nortriptyline 25–100 mg/day (with titration)
Desipramine titrate from 12.5 to 100–150 mg/day
Warning. Opioids are not recommended for DSPN pain as first-, second-, or third-line agents given their high risk of addiction, abuse, and serious adverse events.
Diabetic autonomic neuropathies
CANLightheadednessReduced HRVDocument symptomsPrevention
WeaknessResting tachycardia (>100 bpm)Document signsGlucose control targeting near-normal glycemia: strong evidence for type 1 diabetes, controversial data for type 2 diabetes
FaintnessExercise intoleranceConsider ECG recordings with deep breathingLifestyle modifications: emerging as effective treatment strategies in patients with impaired glucose tolerance/metabolic syndrome, and type 2 diabetes
PalpitationsOrthostatic hypotension (a fall in systolic or diastolic blood pressure of >20 or >10 mmHg, respectively, upon standing)Differential (as applicable):Treatment for orthostatic hypotension
Note. All symptoms occur upon standing.HyperthyroidismPhysical activity
DehydrationVolume repletion with fluids
Adrenal insufficiencyPharmacological:
SmokingMidodrine* (peripheral, selective, direct α1-adrenoreceptor agonist); 2.5–10 mg up to 3 times/day, with titration; use lowest effective dose, first dose before arising
AlcoholDroxidopa** (α/β adrenergic agonist)
CaffeineDietary changes
Medications (e.g., sympathomimetics, over-the-counter cold agents containing ephedrine or pseudoephedrine, recreational drugs, and dietary supplements)Eating multiple small meals
Gastrointestinal neuropathy (gastroparesis)Early satietyClinically silent in the majority of casesCareful medication historyDecreasing fat and fiber intake
Fullness and bloatingGlucose variability and unexplained hypoglycemia (due to the dissociation between food absorption and the pharmacokinetic profiles of insulin and other agents)Esophagogastroduodenoscopy or barium study to exclude organic causes of gastric outlet obstruction or peptic ulcer diseaseWithdrawing drugs with effects on motility: opioids, anticholinergics, tricyclic antidepressants, GLP-1 receptor agonists, pramlintide
Nausea, vomiting, or dyspepsiaGastric emptying with scintigraphy of digestible solids (gold standard if above tests are negative)Medication
Abdominal pain13C-octanoic acid breath test (emerged as an easier alternative)Metoclopramide*** 5–10 mg 3–4 times/day (prokinetic agent, weak evidence, risk of serious adverse effects, tardive dyskinesia)
Note. Symptoms are nonspecific and do not correspond with severity of gastroparesis or abnormal gastric emptying
  • Adapted from ref. 1.

  • * FDA-approved.

  • ** FDA-approved for the treatment of neurogenic orthostatic hypotension but not specifically for orthostatic hypotension due to diabetes.

  • *** FDA-approved for up to 5 days of use.