Diabetic Neuropathy¶

DIAGNOSIS: Diabetic Peripheral Neuropathy ICD-10: G63.2 (Diabetic polyneuropathy); E11.42 (Type 2 DM with diabetic polyneuropathy); E10.42 (Type 1 DM with diabetic polyneuropathy) SCOPE: Distal symmetric polyneuropathy (most common), painful diabetic neuropathy treatment, foot care, and screening for other diabetic neuropathy types. Excludes diabetic amyotrophy (separate protocol) and autonomic neuropathy (mentioned but not primary focus).

STATUS: Draft - Pending Review

PRIORITY KEY: STAT = Immediate | URGENT = Within hours | ROUTINE = Standard | EXT = Extended/atypical cases | - = Not applicable to this setting

SECTION A: ACTION ITEMS¶

1. LABORATORY WORKUP¶

1A. Essential/Core Labs¶

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
HbA1c	Assess glycemic control; primary modifiable risk factor	<7% (individualized goals for elderly)	-	ROUTINE	ROUTINE	-
Fasting glucose	Current glycemic status	70-130 mg/dL	STAT	ROUTINE	ROUTINE	-
BMP (including creatinine, eGFR)	Renal function for medication dosing; CKD common in diabetes	eGFR >60 preferred; adjust meds if lower	STAT	ROUTINE	ROUTINE	-
Lipid panel	Cardiovascular risk; dyslipidemia common comorbidity	LDL <100 mg/dL (or <70 if ASCVD)	-	ROUTINE	ROUTINE	-
Vitamin B12	Metformin causes B12 deficiency; mimics diabetic neuropathy	>300 pg/mL (>400 optimal)	-	ROUTINE	ROUTINE	-
TSH	Hypothyroidism causes neuropathy; common comorbidity	0.4-4.0 mIU/L	-	ROUTINE	ROUTINE	-
CBC	Anemia evaluation; baseline	Normal	STAT	ROUTINE	ROUTINE	-

1B. Extended Workup (Second-line)¶

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
Methylmalonic acid (MMA)	More sensitive for B12 deficiency if B12 borderline	Normal	-	ROUTINE	ROUTINE	-
Folate	Deficiency contributes to neuropathy	>3 ng/mL	-	ROUTINE	ROUTINE	-
Vitamin D	Deficiency associated with neuropathic pain	>30 ng/mL	-	ROUTINE	ROUTINE	-
SPEP/UPEP with immunofixation	Rule out paraproteinemia if atypical features	No monoclonal protein	-	ROUTINE	ROUTINE	-
ANA	Autoimmune/vasculitic neuropathy if atypical	Negative	-	EXT	ROUTINE	-
ESR, CRP	Inflammatory markers if vasculitis suspected	Normal	-	ROUTINE	ROUTINE	-
Hepatitis B, C serologies	Hepatitis C associated with neuropathy; prevalence in diabetics	Negative	-	ROUTINE	ROUTINE	-
HIV	HIV neuropathy if risk factors	Negative	-	EXT	EXT	-

1C. Rare/Specialized (Refractory or Atypical)¶

Test	Rationale	Target Finding	ED	HOSP	OPD	ICU
Cryoglobulins	Cryoglobulinemic neuropathy (esp. with Hep C)	Negative	-	-	EXT	-
Anti-MAG antibodies	IgM paraprotein-associated neuropathy	Negative	-	-	EXT	-
Genetic neuropathy panel (CMT genes)	Family history; atypical presentation	Negative	-	-	EXT	-
Nerve biopsy	Vasculitic neuropathy suspected; atypical non-length-dependent	Diagnostic findings	-	-	EXT	-
Skin biopsy for IENFD	Quantify small fiber neuropathy	Reduced intraepidermal nerve fiber density	-	-	ROUTINE	-

2. DIAGNOSTIC IMAGING & STUDIES¶

2A. Essential/First-line¶

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
Monofilament testing (10g)	At every diabetic visit; annually minimum	Intact sensation 8-10 sites	None	-	ROUTINE	ROUTINE	-
Tuning fork (128 Hz)	Vibration sense at great toe	Intact vibration sense	None	-	ROUTINE	ROUTINE	-
Ankle reflexes	Deep tendon reflex assessment	Present (may be diminished/absent in neuropathy)	None	-	ROUTINE	ROUTINE	-
Foot examination	Inspect for ulcers, calluses, deformities, pulses	No ulcers or pre-ulcerative lesions	None	STAT	ROUTINE	ROUTINE	-

2B. Extended¶

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
EMG/NCS (nerve conduction study)	Atypical presentation; asymmetric; rapid progression	Length-dependent sensory > motor polyneuropathy	Anticoagulation (relative for EMG)	-	ROUTINE	ROUTINE	-
Autonomic testing (QSART, HR variability, tilt table)	Symptoms of autonomic neuropathy; syncope; gastroparesis	Abnormal sudomotor, cardiovagal, or adrenergic function	None	-	EXT	ROUTINE	-
MRI lumbar spine	Radiculopathy suspected; focal deficits	Rule out compressive lesion	MRI contraindications	URGENT	ROUTINE	ROUTINE	-

2C. Rare/Specialized¶

Study	Timing	Target Finding	Contraindications	ED	HOSP	OPD	ICU
Skin biopsy (punch biopsy at ankle and thigh)	Confirm small fiber neuropathy; normal NCS	Reduced IENFD (<threshold for age/sex)	Bleeding diathesis; anticoagulation	-	-	ROUTINE	-
Corneal confocal microscopy	Research; non-invasive small fiber assessment	Reduced corneal nerve fiber length/density	None	-	-	EXT	-
Sudoscan	Screening for sudomotor dysfunction; small fiber	Abnormal electrochemical skin conductance	None	-	-	EXT	-

3. TREATMENT¶

3A. Acute/Emergent¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Wound care	Topical	Diabetic foot ulcer	Debridement; offloading; appropriate dressing :: Topical :: :: Wound assessment; debridement if needed; offload pressure; moist wound healing	None	Signs of infection; healing progress	STAT	STAT	ROUTINE	-
Antibiotics (diabetic foot infection)	PO/IV	Infected diabetic foot ulcer	Per culture/severity :: PO/IV :: :: Mild: oral (cephalexin, amox/clav); Moderate-severe: IV (piptazo, vanc); per wound culture	Drug allergy	Infection markers; wound healing	STAT	STAT	-	-
Pain crisis management	IV/PO	Severe acute neuropathic pain flare	Multimodal :: IV/PO :: :: Consider IV lidocaine if refractory; short-term low-dose opioid for acute crisis	Per specific agent	Pain scores; sedation	URGENT	URGENT	-	-

3B. Symptomatic Treatments (Neuropathic Pain - First-line)¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Duloxetine	PO	First-line for painful diabetic neuropathy; FDA-approved	30 mg daily; 60 mg daily :: PO :: :: Start 30 mg daily x 1 week; increase to 60 mg daily; max 120 mg/day (limited evidence for higher doses)	MAOIs; uncontrolled glaucoma; severe renal impairment (CrCl <30)	Hepatic function; BP; suicidal ideation	-	ROUTINE	ROUTINE	-
Pregabalin	PO	First-line; FDA-approved for DPN	50 mg TID; 75 mg BID; 100 mg TID; 150 mg BID; 200 mg TID :: PO :: :: Start 50 mg TID or 75 mg BID; titrate q3-7d based on response; max 300 mg/day (CrCl 30-60: reduce dose)	Angioedema to pregabalin/gabapentin	Dizziness, somnolence, weight gain, peripheral edema	-	ROUTINE	ROUTINE	-
Gabapentin	PO	First-line alternative; less expensive; similar efficacy	300 mg qHS; 300 mg TID; 600 mg TID; 900 mg TID; 1200 mg TID :: PO :: :: Start 300 mg qHS; titrate by 300 mg q3-7d; target 1800-3600 mg/day divided TID; reduce dose if CrCl <60	Severe renal impairment (dose adjust)	Same as pregabalin; less edema	-	ROUTINE	ROUTINE	-
Amitriptyline	PO	TCA option; also helps sleep; less expensive	10 mg qHS; 25 mg qHS; 50 mg qHS; 75 mg qHS; 100 mg qHS :: PO :: :: Start 10-25 mg qHS; titrate by 10-25 mg q1-2wk; typical 25-75 mg qHS; max 150 mg	Cardiac conduction abnormality; recent MI; urinary retention; glaucoma; elderly (use with caution)	ECG if >40y or cardiac history; anticholinergic effects	-	ROUTINE	ROUTINE	-
Nortriptyline	PO	TCA with less sedation and anticholinergic effects than amitriptyline	10 mg qHS; 25 mg qHS; 50 mg qHS; 75 mg qHS :: PO :: :: Start 10-25 mg qHS; titrate by 10-25 mg q1-2wk; typical 25-75 mg qHS	Same as amitriptyline	Same as amitriptyline; ECG if >100 mg	-	ROUTINE	ROUTINE	-
Venlafaxine XR	PO	SNRI alternative to duloxetine	37.5 mg daily; 75 mg daily; 150 mg daily; 225 mg daily :: PO :: :: Start 37.5 mg daily; titrate by 37.5-75 mg q1wk; target 150-225 mg daily	MAOIs; uncontrolled HTN	BP at higher doses; withdrawal if abrupt discontinuation	-	ROUTINE	ROUTINE	-

3C. Second-line/Refractory (Neuropathic Pain)¶

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Capsaicin 8% patch (Qutenza)	Topical	Localized neuropathic pain; add-on therapy	Apply for 30 min :: Topical :: :: Applied by healthcare provider; local anesthetic pre-treatment; repeat q3mo	Application to face; broken skin	Local pain during application; burning	-	-	ROUTINE	-
Lidocaine 5% patch	Topical	Localized pain; adjunctive therapy	1-3 patches to painful area :: Topical :: :: Apply to most painful area; up to 3 patches for 12h on/12h off	Allergy to local anesthetics	Skin irritation	-	ROUTINE	ROUTINE	-
Tapentadol ER	PO	Refractory pain; opioid with norepinephrine reuptake inhibition	50 mg BID; 100 mg BID; 150 mg BID; 200 mg BID; 250 mg BID :: PO :: :: Start 50 mg BID; titrate by 50 mg BID q3d; max 500 mg/day; FDA-approved for DPN	Severe respiratory depression; MAOIs; paralytic ileus	Constipation, sedation, respiratory status	-	EXT	ROUTINE	-
Tramadol	PO	Moderate pain; opioid-like with serotonergic properties	50 mg q6h PRN; 100 mg ER BID :: PO :: :: Start 50 mg q6h PRN; max 400 mg/day; reduce if renal/hepatic impairment	Seizure disorder; concurrent MAOIs/SSRIs (serotonin syndrome risk)	Seizures, serotonin syndrome, sedation	-	ROUTINE	ROUTINE	-
Desipramine	PO	TCA with minimal anticholinergic effects	25 mg qHS; 50 mg qHS; 100 mg qHS :: PO :: :: Start 25 mg qHS; titrate by 25 mg q1-2wk; target 50-100 mg	Same as other TCAs	ECG; therapeutic drug monitoring available	-	ROUTINE	ROUTINE	-
Oxcarbazepine	PO	Second-line anticonvulsant; less evidence	300 mg BID; 600 mg BID :: PO :: :: Start 300 mg BID; titrate by 300 mg/wk; typical 600-1200 mg/day	Hyponatremia risk	Sodium level; rash (SJS rare)	-	-	ROUTINE	-
Combination therapy	Various	Inadequate response to single agent	Combine agents from different classes :: Various :: :: Use lower doses of each; duloxetine + pregabalin; TCA + gabapentinoid	Per individual agents	Additive side effects	-	ROUTINE	ROUTINE	-
Buprenorphine patch	TD	Severe refractory pain; opioid option	5 mcg/hr; 10 mcg/hr; 20 mcg/hr :: TD :: :: Start 5 mcg/hr weekly patch; titrate slowly	Severe respiratory depression; QT prolongation	Respiratory status, QTc	-	EXT	ROUTINE	-
Spinal cord stimulation	Implant	Refractory painful DPN; failed multiple medications	Per implant protocol :: Implant :: :: Trial stimulation before permanent; high-frequency or burst stimulation	Infection; coagulopathy; psychiatric instability	Device function; pain relief	-	-	EXT	-

3D. Disease-Modifying / Preventive Therapies¶

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Glycemic control optimization	Various	Primary prevention and slowing progression	HbA1c target <7% :: Various :: :: Individualized; tighter control (6-6.5%) in younger patients; less strict (7.5-8%) in elderly/comorbid	None	Hypoglycemia risk	HbA1c q3mo until at goal, then q6mo	-	ROUTINE	ROUTINE	-
Alpha-lipoic acid	PO/IV	Antioxidant; European data for DPN	600 mg daily; 600 mg IV daily :: PO/IV :: :: 600 mg PO daily; IV form (600 mg daily x 3wk) for acute symptom relief; limited evidence	None	GI upset; may lower glucose	Glucose (may enhance insulin sensitivity)	-	ROUTINE	ROUTINE	-
Vitamin B12 supplementation	PO/IM	B12 deficiency or metformin use	1000 mcg PO daily; 1000 mcg IM monthly :: PO/IM :: :: 1000-2000 mcg PO daily; or 1000 mcg IM monthly if poor absorption	None	None	B12 level q6-12mo	-	ROUTINE	ROUTINE	-
Benfotiamine	PO	Thiamine derivative; AGE inhibition	300 mg BID :: PO :: :: 300 mg BID; limited evidence	None	GI upset	None specific	-	-	ROUTINE	-
ACE inhibitor or ARB	PO	Nephroprotection; may slow neuropathy progression	Per agent :: PO :: :: Standard doses; benefit for kidney protection proven; neuropathy benefit theoretical	Angioedema; pregnancy; hyperkalemia; bilateral RAS	K+, creatinine	-	ROUTINE	ROUTINE	-
Statin therapy	PO	Cardiovascular protection; anti-inflammatory	Per agent :: PO :: :: High-intensity statin for most diabetics	Active liver disease	LFTs, myalgias	-	ROUTINE	ROUTINE	-

4. OTHER RECOMMENDATIONS¶

4A. Referrals & Consults¶

Recommendation	ED	HOSP	OPD	ICU
Endocrinology for diabetes optimization if HbA1c not at goal or complex regimen needed	-	ROUTINE	ROUTINE	-
Podiatry for foot exam, nail care, custom orthotics, and offloading devices	-	ROUTINE	ROUTINE	-
Vascular surgery if peripheral arterial disease suspected (ABI <0.9 or absent pulses)	URGENT	URGENT	ROUTINE	-
Pain management for refractory neuropathic pain and interventional options (SCS)	-	-	ROUTINE	-
Physical therapy for balance training and gait assessment to reduce fall risk	-	ROUTINE	ROUTINE	-
Wound care specialist for diabetic foot ulcers not healing with standard care	-	URGENT	ROUTINE	-
Ophthalmology for annual diabetic retinopathy screening	-	-	ROUTINE	-
Nephrology if eGFR <30 or rapidly declining renal function	-	ROUTINE	ROUTINE	-

4B. Patient Instructions¶

Recommendation	ED	HOSP	OPD
Inspect feet daily using mirror for soles; look for cuts, blisters, redness, or swelling	-	ROUTINE	ROUTINE
Never walk barefoot, even indoors, to prevent foot injuries	-	ROUTINE	ROUTINE
Wear properly fitted shoes with adequate support; have shoes fitted by professional	-	ROUTINE	ROUTINE
Test bath water temperature with elbow (not feet) to prevent burns from impaired sensation	-	ROUTINE	ROUTINE
Report any foot wounds, color changes, or pain immediately as diabetic foot ulcers can progress rapidly	STAT	STAT	ROUTINE
Take all prescribed medications as directed; do not skip doses of pain medications abruptly	-	ROUTINE	ROUTINE
Monitor blood glucose as directed; excellent glycemic control is the most important factor to slow progression	-	ROUTINE	ROUTINE
Avoid alcohol which can worsen neuropathy and interact with pain medications	-	ROUTINE	ROUTINE

4C. Lifestyle & Prevention¶

Recommendation	ED	HOSP	OPD
Optimal glycemic control (HbA1c <7%) is the primary intervention to prevent and slow neuropathy progression	-	ROUTINE	ROUTINE
Smoking cessation as smoking worsens peripheral vascular disease and neuropathy	-	ROUTINE	ROUTINE
Blood pressure control (<130/80) reduces microvascular complications	-	ROUTINE	ROUTINE
LDL cholesterol control with statin therapy reduces cardiovascular risk	-	ROUTINE	ROUTINE
Regular physical activity (150 min/week moderate) improves glycemic control and overall health	-	ROUTINE	ROUTINE
Healthy diet (Mediterranean or DASH) supports glycemic and cardiovascular goals	-	ROUTINE	ROUTINE
Limit alcohol which worsens neuropathy independently and affects glycemic control	-	ROUTINE	ROUTINE
Annual comprehensive foot examination by healthcare provider	-	-	ROUTINE
Fall prevention with home safety modifications given impaired proprioception	-	ROUTINE	ROUTINE

SECTION B: REFERENCE¶

5. DIFFERENTIAL DIAGNOSIS¶

Alternative Diagnosis	Key Distinguishing Features	Tests to Differentiate
B12 deficiency neuropathy	Sensory > motor; may have subacute combined degeneration; metformin use	B12, MMA levels
Chronic inflammatory demyelinating polyneuropathy (CIDP)	Motor involvement; areflexia; elevated CSF protein; demyelinating NCS	EMG/NCS (demyelinating pattern); CSF protein
Uremic neuropathy	Advanced CKD (eGFR <15); improves with dialysis	BUN, creatinine, eGFR
Alcoholic neuropathy	Heavy alcohol use history; painful; coexisting thiamine deficiency	History; thiamine level
Hypothyroid neuropathy	Other hypothyroid symptoms; CTS common	TSH, free T4
Paraproteinemic neuropathy	IgM most common; anti-MAG antibodies; may have ataxia	SPEP/UPEP; immunofixation; anti-MAG
Chemotherapy-induced neuropathy	Temporal relationship with chemotherapy (platinum, taxanes, vincristine)	Medication history
Hereditary neuropathy (CMT)	Family history; high arches (pes cavus); hammer toes; slowly progressive	Genetic testing; NCS pattern
Vasculitic neuropathy	Asymmetric; mononeuritis multiplex pattern; systemic symptoms	Nerve biopsy; inflammatory markers; angiography
Amyloid neuropathy	Autonomic involvement; cardiomyopathy; carpal tunnel; paraprotein may be present	Fat pad or nerve biopsy; genetic testing (TTR); SPEP

6. MONITORING PARAMETERS¶

Parameter	Frequency	Target/Threshold	Action if Abnormal	ED	HOSP	OPD	ICU
HbA1c	Every 3-6 months	<7% (individualized)	Intensify diabetes management	-	ROUTINE	ROUTINE	-
Comprehensive foot exam	Annually (more often if high risk)	No ulcers, intact sensation, intact skin	Podiatry referral; offloading; wound care	-	ROUTINE	ROUTINE	-
Monofilament testing	At least annually	Intact sensation at ≥8/10 sites	High-risk foot care; education	-	ROUTINE	ROUTINE	-
Pain scores (VAS, NRS)	Each visit	50%+ reduction with treatment	Adjust therapy; consider combination or referral	-	ROUTINE	ROUTINE	-
B12 level	Annually if on metformin	>300 pg/mL	Supplement B12	-	ROUTINE	ROUTINE	-
Kidney function (eGFR)	At least annually	eGFR >60; stable	Adjust medication doses; nephrology referral if declining	-	ROUTINE	ROUTINE	-
Blood pressure	Each visit	<130/80 mmHg	Optimize antihypertensives	-	ROUTINE	ROUTINE	-
Autonomic symptoms screen	Each visit	No symptoms	Autonomic testing; cardiology referral if cardiac autonomic neuropathy	-	ROUTINE	ROUTINE	-
Depression screen (PHQ-9)	Annually or if symptoms	Negative	Treatment; referral	-	ROUTINE	ROUTINE	-

7. DISPOSITION CRITERIA¶

Disposition	Criteria
Discharge home	Symptoms managed; no foot infection; follow-up arranged
Admit to floor	Diabetic foot infection requiring IV antibiotics; severe uncontrolled pain; associated acute kidney injury
Surgical admission	Foot infection requiring debridement or amputation
Outpatient follow-up	Every 3-6 months for medication optimization; annually for comprehensive foot exam

8. EVIDENCE & REFERENCES¶

Recommendation	Evidence Level	Source
Duloxetine for painful DPN (FDA-approved)	Class I, Level A	Wernicke et al. Neurology 2006
Pregabalin for painful DPN (FDA-approved)	Class I, Level A	Derry et al. Cochrane 2019
Gabapentin effective for DPN	Class II, Level B	Wiffen et al. Cochrane 2017
Tricyclic antidepressants effective	Class II, Level B	Moore et al. Cochrane 2015
Glycemic control prevents neuropathy progression	Class I, Level A	DCCT/EDIC Research Group. NEJM 1993
Alpha-lipoic acid may improve symptoms	Class II, Level B	Ziegler et al. Diabetes Care 2011
Comprehensive foot exam reduces amputations	Class II, Level B	ADA Standards of Care 2024 (Section 12)
Tapentadol effective for DPN (FDA-approved)	Class I, Level A	Vinik et al. Diabetes Care 2014
Spinal cord stimulation for refractory DPN	Class II, Level B	Slangen et al. Diabetes Care 2014
Capsaicin 8% patch effective	Class I, Level A	Simpson et al. Pain 2017

CHANGE LOG¶

v1.0 (January 27, 2026) - Initial template creation - Comprehensive neuropathic pain management - Includes FDA-approved agents (duloxetine, pregabalin, tapentadol) - Foot care and ulcer prevention emphasis - Structured dosing format for order sentence generation

APPENDIX A: Diabetic Foot Risk Classification¶

Risk Category	Features	Foot Exam Frequency	Recommendations
Low risk	Normal sensation; no deformity; palpable pulses	Annually	Education; appropriate footwear
Moderate risk	Loss of protective sensation OR peripheral artery disease OR foot deformity	Every 3-6 months	Podiatry referral; custom footwear consideration
High risk	Previous ulcer OR previous amputation OR end-stage renal disease	Every 1-3 months	Podiatry; vascular evaluation; offloading devices
Active ulcer or infection	Current ulcer/infection	As needed until healed	Wound care team; vascular surgery if ischemic

APPENDIX B: Types of Diabetic Neuropathy¶

Type	Clinical Features	Typical Onset	Prognosis
Distal symmetric polyneuropathy (DSPN)	Stocking-glove sensory loss; burning pain; numbness; length-dependent	Insidious	Chronic; preventable progression with glycemic control
Diabetic autonomic neuropathy	Orthostatic hypotension; gastroparesis; erectile dysfunction; sudomotor dysfunction; cardiac denervation	Gradual	Variable; cardiac autonomic neuropathy increases mortality
Diabetic lumbosacral radiculoplexus neuropathy (diabetic amyotrophy)	Acute/subacute proximal leg weakness and pain; weight loss; often unilateral then spreads	Acute-subacute	Usually monophasic; recovery over months-years
Diabetic thoracic radiculopathy	Truncal pain/dysesthesia; dermatomal distribution; may mimic visceral disease	Acute-subacute	Self-limited (months)
Cranial neuropathy	CN III most common (pupil-sparing); CN VI, VII also affected	Acute	Usually resolves in 3-6 months
Mononeuropathy/entrapment	Carpal tunnel syndrome; ulnar neuropathy; peroneal neuropathy	Variable	Treat underlying entrapment
Treatment-induced neuropathy of diabetes (TIND)	Acute painful small fiber neuropathy after rapid glucose improvement	After aggressive glycemic control	Usually improves with slower glucose normalization