Diabetic Neuropathy

VERSION: 1.0 CREATED: January 29, 2026 REVISED: January 29, 2026 STATUS: Approved

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DIAGNOSIS: Diabetic Neuropathy

ICD-10: E11.40 (Type 2 diabetes with diabetic neuropathy, unspecified), E11.41 (Type 2 diabetes with diabetic mononeuropathy), E11.42 (Type 2 diabetes with diabetic polyneuropathy), E10.40-E10.42 (Type 1 equivalents), G63.2 (Diabetic polyneuropathy), G62.9 (Polyneuropathy, unspecified)

CPT CODES: 83036 (HbA1c), 82947 (Fasting glucose), 80048 (BMP), 85025 (CBC), 82607 (Vitamin B12), 83921 (Methylmalonic acid (MMA)), 84443 (TSH), 80061 (Lipid panel), 80076 (Liver function tests), 87389 (HIV), 86592 (RPR/VDRL), 85652 (ESR), 86235 (ANA), 95907-95913 (Nerve conduction studies (NCS)), 95886 (Electromyography (EMG)), 95924 (Cardiovascular autonomic reflex tests), 11104 (Skin punch biopsy (IENFD)), 72148 (MRI lumbosacral plexus), 72141 (MRI spine), 96365 (IVIG (severe/refractory)), 96374 (Methylprednisolone)

SYNONYMS: Diabetic peripheral neuropathy, DPN, diabetic polyneuropathy, diabetic sensorimotor neuropathy, diabetic autonomic neuropathy, painful diabetic neuropathy, PDN, diabetic amyotrophy, diabetic lumbosacral radiculoplexus neuropathy, DLRPN, proximal diabetic neuropathy, diabetic nerve damage

SCOPE: Evaluation and management of diabetic neuropathy in adults including distal symmetric polyneuropathy (most common), painful diabetic neuropathy, diabetic autonomic neuropathy, and focal/multifocal neuropathies. Applies to ED, hospital, and outpatient settings.

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DEFINITIONS: - Distal Symmetric Polyneuropathy (DSPN): Most common form (~75%); length-dependent sensorimotor neuropathy; "stocking-glove" distribution - Painful Diabetic Neuropathy (PDN): DSPN with prominent neuropathic pain; affects 20-25% of diabetic patients - Diabetic Autonomic Neuropathy (DAN): Affects cardiovascular, GI, genitourinary, sudomotor systems - Diabetic Amyotrophy (DLRPN): Acute/subacute proximal leg weakness and pain; often asymmetric; immune-mediated - Small Fiber Neuropathy: Early DPN affecting small unmyelinated fibers; pain/temperature loss, burning pain - Cardiovascular Autonomic Neuropathy (CAN): Resting tachycardia, orthostatic hypotension, QTc prolongation

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

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1. LABORATORY WORKUP

1A. Core Labs (All Patients)

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
HbA1c (CPT 83036)	-	ROUTINE	ROUTINE	-	Glycemic control; correlates with neuropathy risk	<7% (individualized)
Fasting glucose (CPT 82947)	ROUTINE	ROUTINE	ROUTINE	-	Current glycemic status	80-130 mg/dL
BMP (CPT 80048)	ROUTINE	ROUTINE	ROUTINE	ROUTINE	Renal function; uremic neuropathy	Normal
CBC (CPT 85025)	ROUTINE	ROUTINE	ROUTINE	-	Anemia (B12 deficiency)	Normal
Vitamin B12 (CPT 82607)	-	ROUTINE	ROUTINE	-	Metformin causes B12 deficiency; coexistent deficiency	>400 pg/mL
Methylmalonic acid (MMA) (CPT 83921)	-	ROUTINE	ROUTINE	-	If B12 borderline (200-400)	Normal
TSH (CPT 84443)	-	ROUTINE	ROUTINE	-	Hypothyroid neuropathy	Normal
Lipid panel (CPT 80061)	-	ROUTINE	ROUTINE	-	Dyslipidemia contributes to neuropathy	LDL <100 (or <70 if ASCVD)

1B. Extended Labs (Atypical Presentations)

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
SPEP/UPEP with immunofixation (CPT 86334, 86335)	-	ROUTINE	ROUTINE	-	Monoclonal gammopathy-associated neuropathy	No M-spike
Serum free light chains	-	ROUTINE	ROUTINE	-	If SPEP negative but suspicion	Normal ratio
Liver function tests (CPT 80076)	-	ROUTINE	ROUTINE	-	Hepatic disease, alcohol	Normal
HIV (CPT 87389)	-	ROUTINE	EXT	-	If risk factors	Negative
RPR/VDRL (CPT 86592)	-	ROUTINE	EXT	-	Syphilis if atypical	Nonreactive
ESR (CPT 85652), CRP (CPT 86140)	-	ROUTINE	EXT	-	Inflammatory/vasculitic neuropathy	Normal
ANA (CPT 86235)	-	-	EXT	-	If connective tissue disease suspected	Negative
Anti-GAD65, IA-2 antibodies (CPT 86235)	-	-	EXT	-	If type uncertain; LADA	Document

1C. Specialized Labs (Diabetic Amyotrophy/Atypical)

Test	ED	HOSP	OPD	ICU	Rationale	Target Finding
CSF analysis (CPT 89051, 84157, 82945)	-	EXT	EXT	-	Elevated protein in DLRPN; r/o inflammatory	Mild protein elevation in DLRPN
Paraneoplastic panel	-	EXT	EXT	-	If rapid progression, weight loss	Negative

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2. DIAGNOSTIC IMAGING & STUDIES

2A. Electrodiagnostic Studies

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
Nerve conduction studies (NCS) (CPT 95907-95913)	-	ROUTINE	ROUTINE	-	Baseline; atypical cases	Axonal sensorimotor polyneuropathy	Pacemaker (relative); anticoagulation (relative)
Electromyography (EMG) (CPT 95886)	-	ROUTINE	ROUTINE	-	If motor involvement; amyotrophy	Denervation in affected muscles	Active infection at site
Quantitative sensory testing (QST)	-	-	EXT	-	Small fiber neuropathy; research	Abnormal thermal thresholds	None

2B. Autonomic Testing

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
Cardiovascular autonomic reflex tests (CPT 95924)	-	-	ROUTINE	-	If CAN suspected	Abnormal HR variability, Valsalva ratio	Arrhythmias
Tilt table test (CPT 95924)	-	-	ROUTINE	-	Orthostatic hypotension evaluation	Orthostatic BP drop without HR rise	Severe coronary disease
Sudomotor function (QSART) (CPT 95924)	-	-	EXT	-	Sudomotor dysfunction	Reduced sweat output	None
Gastric emptying study	-	-	ROUTINE	-	If gastroparesis suspected	Delayed emptying	None

2C. Small Fiber Neuropathy Assessment

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
Skin punch biopsy (IENFD) (CPT 11104)	-	-	ROUTINE	-	Small fiber neuropathy; normal NCS	Reduced intraepidermal nerve fiber density	Anticoagulation (relative)
Corneal confocal microscopy	-	-	EXT	-	Non-invasive small fiber assessment	Reduced corneal nerve fiber density	None

2D. Imaging (Select Cases)

Study	ED	HOSP	OPD	ICU	Timing	Target Finding	Contraindications
MRI lumbosacral plexus (CPT 72148)	-	ROUTINE	EXT	-	Diabetic amyotrophy; asymmetric weakness	Plexus/root enhancement in DLRPN	Pacemaker, metal
MRI spine (CPT 72141)	URGENT	URGENT	EXT	-	R/o structural if myelopathy suspected	R/o compression	Same

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3. TREATMENT

3A. Glycemic Control (Foundation of Treatment)

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Intensive glycemic control	-	-	7% :: - :: - :: Target HbA1c <7% (individualized); avoid hypoglycemia	Hypoglycemia unawareness with CAN	HbA1c q3 months until stable	-	ROUTINE	ROUTINE	-
Continuous glucose monitoring	-	-	N/A :: - :: per protocol :: If hypoglycemia unawareness	None	Sensor accuracy	-	-	ROUTINE	-

3B. Neuropathic Pain - First-Line Agents

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Duloxetine (Cymbalta)	PO	-	30 mg :: PO :: daily :: 30 mg daily × 1 week, then 60 mg daily; max 120 mg/day	MAOIs, uncontrolled glaucoma, hepatic impairment	Nausea, BP; serotonin syndrome	-	ROUTINE	ROUTINE	-
Pregabalin (Lyrica)	PO	-	50 mg :: PO :: TID :: 50 mg TID or 75 mg BID; titrate to 300 mg/day; max 600 mg/day	CrCl <60: reduce dose	Sedation, edema, weight gain; renal dosing	-	ROUTINE	ROUTINE	-
Gabapentin (Neurontin)	PO	-	300 mg :: PO :: QHS :: 300 mg QHS, titrate by 300 mg q3-7 days; target 1800-3600 mg/day divided TID	CrCl <60: reduce dose	Sedation, edema; renal dosing	ROUTINE	ROUTINE	ROUTINE	-

3C. Neuropathic Pain - Second-Line Agents

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Venlafaxine XR	PO	-	37.5-75 mg :: PO :: daily :: 37.5-75 mg daily; titrate to 150-225 mg/day	MAOIs, uncontrolled HTN	BP; serotonin syndrome	-	ROUTINE	ROUTINE	-
Amitriptyline	-	-	10-25 mg :: PO :: QHS :: 10-25 mg QHS; titrate to 50-100 mg QHS	Cardiac disease, glaucoma, urinary retention	ECG if >100 mg; anticholinergic effects	-	ROUTINE	ROUTINE	-
Nortriptyline	-	-	10-25 mg :: PO :: QHS :: 10-25 mg QHS; titrate to 75 mg QHS	Same as amitriptyline	Same; fewer anticholinergic effects	-	ROUTINE	ROUTINE	-

3D. Neuropathic Pain - Topical Agents

Treatment	Route	Indication	Dosing	Pre-Treatment Requirements	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Capsaicin 8% patch (Qutenza)	Transdermal	-	N/A :: Transdermal :: per protocol :: Apply to painful area × 30-60 min q3 months; in-office	-	Open wounds; capsaicin allergy	BP during application; pain	-	-	ROUTINE	-
Lidocaine 5% patch	Transdermal	-	N/A :: Transdermal :: daily :: Up to 3 patches daily; 12h on/12h off	-	Allergy to local anesthetics	Local irritation	-	ROUTINE	ROUTINE	-
Capsaicin cream 0.075%	-	-	N/A :: - :: TID-QID :: Apply TID-QID; takes 2-4 weeks for effect	-	Open wounds	Initial burning (improves)	-	-	ROUTINE	-

3E. Neuropathic Pain - Third-Line/Refractory

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Tramadol	PO	-	50-100 mg :: PO :: PRN :: 50-100 mg q4-6h PRN; max 400 mg/day	Seizure disorder, opioid dependence, MAOIs	Seizures; serotonin syndrome; dependence	-	ROUTINE	ROUTINE	-
Tapentadol ER	PO	-	50 mg :: PO :: BID :: 50 mg BID; titrate by 50 mg q3 days; max 500 mg/day	Respiratory depression, severe hepatic impairment	Respiratory; GI effects	-	-	ROUTINE	-
Spinal cord stimulation	-	-	N/A :: - :: continuous :: Referral to interventional pain for refractory cases	Infection, coagulopathy	Device complications	-	-	EXT	-

3F. Combination Therapy

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Duloxetine + Pregabalin	-	-	N/A :: - :: per protocol :: If monotherapy inadequate; use lower doses of each	Per individual agents	Per individual agents	-	ROUTINE	ROUTINE	-
Gabapentinoid + TCA	-	-	N/A :: - :: per protocol :: If monotherapy inadequate	Per individual agents	Sedation; anticholinergic	-	ROUTINE	ROUTINE	-

3G. Diabetic Autonomic Neuropathy Treatment

Symptom	Treatment	Dosing	Monitoring
Orthostatic hypotension	Midodrine	2.5-10 mg :: - :: TID :: 2.5-10 mg TID (last dose before 6 PM)	Supine HTN; avoid at night
	Fludrocortisone	0.1-0.3 mg :: - :: daily :: 0.1-0.3 mg daily	Edema, K+, supine HTN
	Droxidopa (Northera)	100-600 mg :: - :: TID :: 100-600 mg TID	Supine HTN
	Compression stockings	N/A :: - :: continuous :: Waist-high, 30-40 mmHg	Compliance
Gastroparesis	Metoclopramide	5-10 mg :: - :: TID :: 5-10 mg before meals; max 12 weeks	Tardive dyskinesia (black box)
	Domperidone	10 mg :: - :: TID :: 10 mg TID (not FDA-approved, requires access)	QTc prolongation
	Erythromycin	40-250 mg :: - :: TID :: 40-250 mg TID (tachyphylaxis common)	GI symptoms; QTc
	Gastric electrical stimulator	N/A :: - :: continuous :: Refractory cases; surgical	Device complications
Erectile dysfunction	Sildenafil	25-100 mg :: - :: PRN :: 25-100 mg PRN	Nitrate contraindication
	Tadalafil	10-20 mg :: - :: daily :: 10-20 mg PRN or 2.5-5 mg daily	Same
Bladder dysfunction	Timed voiding	N/A :: - :: per protocol :: q3-4 hour schedule	Residual volumes
	Bethanechol	10-50 mg :: - :: TID-QID :: 10-50 mg TID-QID	Asthma, bradycardia
	Intermittent catheterization	N/A :: - :: per protocol :: If high PVR	UTI
Sudomotor dysfunction	Glycopyrrolate	1-2 mg :: - :: TID :: 1-2 mg BID-TID	Anticholinergic effects

3H. Diabetic Amyotrophy (DLRPN) Treatment

Treatment	Route	Indication	Dosing	Contraindications	Monitoring	ED	HOSP	OPD	ICU
Glycemic control	-	-	N/A :: - :: per protocol :: Optimize; avoid rapid correction	Per diabetes management	HbA1c	-	ROUTINE	ROUTINE	-
Physical therapy	-	-	N/A :: - :: daily :: Prevent contractures; strengthen	None	Function	-	ROUTINE	ROUTINE	-
Pain management	-	-	N/A :: - :: per protocol :: Per neuropathic pain algorithm	Per agent	Per agent	-	ROUTINE	ROUTINE	-
IVIG (severe/refractory) (CPT 96365)	PO	-	2 g/kg :: PO :: - :: 2 g/kg over 2-5 days; may repeat	IgA deficiency	Renal function; infusion reactions	-	ROUTINE	EXT	-
Methylprednisolone (CPT 96374)	IV	-	1 g :: IV :: daily :: 1 g IV daily × 3-5 days; taper (may use if IVIG unavailable)	Uncontrolled DM (relative)	Glucose; infection	-	ROUTINE	EXT	-

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4. OTHER RECOMMENDATIONS

4A. Referrals & Consults

Recommendation	ED	HOSP	OPD	ICU	Indication
Neurology	-	ROUTINE	ROUTINE	-	Atypical presentation, diagnosis confirmation, refractory pain
Endocrinology	-	ROUTINE	ROUTINE	-	Diabetes optimization
Podiatry	-	ROUTINE	ROUTINE	-	Foot care, ulcer prevention, nail care
Pain management	-	-	ROUTINE	-	Refractory neuropathic pain
Physical therapy	-	ROUTINE	ROUTINE	-	Balance, gait, strengthening
Occupational therapy	-	-	ROUTINE	-	Hand function, adaptive equipment
Gastroenterology	-	-	ROUTINE	-	Gastroparesis evaluation/management
Urology	-	-	ROUTINE	-	Bladder dysfunction, erectile dysfunction
Cardiology	-	-	ROUTINE	-	Cardiovascular autonomic neuropathy
Wound care	-	URGENT	ROUTINE	-	Diabetic foot ulcers

4B. Foot Care & Ulcer Prevention (Critical)

Recommendation	ED	HOSP	OPD
Daily foot inspection (patient or caregiver)	-	ROUTINE	ROUTINE
Monofilament testing annually (10-g Semmes-Weinstein)	-	ROUTINE	ROUTINE
Protective footwear; never walk barefoot	-	ROUTINE	ROUTINE
Custom orthotics/diabetic shoes for high-risk feet	-	-	ROUTINE
Keep feet clean and dry; moisturize (not between toes)	-	ROUTINE	ROUTINE
Avoid heating pads; test water temperature with elbow	-	ROUTINE	ROUTINE
Trim toenails straight across; professional care if needed	-	ROUTINE	ROUTINE
Immediate evaluation for any wound, blister, or color change	URGENT	URGENT	URGENT

4C. Patient/Family Instructions

Recommendation	ED	HOSP	OPD
Neuropathy is common in diabetes; can be slowed with good control	-	ROUTINE	ROUTINE
Report new numbness, tingling, weakness, or pain	-	ROUTINE	ROUTINE
Daily foot inspection is critical; use mirror if needed	-	ROUTINE	ROUTINE
Never walk barefoot; check shoes for objects before wearing	-	ROUTINE	ROUTINE
Fall prevention: good lighting, remove rugs, use handrails	-	ROUTINE	ROUTINE
Report dizziness on standing, early satiety, urinary symptoms	-	ROUTINE	ROUTINE
American Diabetes Association (diabetes.org) resources	-	-	ROUTINE

4D. Comorbidity Management

Recommendation	ED	HOSP	OPD
Statin therapy for dyslipidemia (reduces neuropathy progression)	-	ROUTINE	ROUTINE
Blood pressure control <140/90 (or <130/80 if tolerated)	-	ROUTINE	ROUTINE
Smoking cessation	-	ROUTINE	ROUTINE
Alcohol moderation (<1 drink/day women, <2 men)	-	ROUTINE	ROUTINE
Weight management	-	-	ROUTINE
SGLT2 inhibitor or GLP-1 RA if ASCVD or CKD	-	ROUTINE	ROUTINE

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5. DIFFERENTIAL DIAGNOSIS

Alternative Diagnosis	Key Distinguishing Features	Tests to Differentiate
B12 deficiency neuropathy	Macrocytic anemia; subacute combined degeneration	B12, MMA; may coexist with DPN
Alcohol-related neuropathy	Alcohol history; nutritional deficiency	History; thiamine; may coexist
Chronic inflammatory demyelinating polyneuropathy	Proximal + distal weakness; demyelinating NCS	NCS pattern; CSF protein
Uremic neuropathy	ESRD; improves with dialysis	Creatinine; dialysis status
Hypothyroid neuropathy	Carpal tunnel; myopathy; slow relaxation reflexes	TSH
Monoclonal gammopathy neuropathy	Often sensory > motor; may have ataxia	SPEP/UPEP; free light chains
Hereditary neuropathy (CMT)	Family history; high arches; hammer toes	Genetic testing; NCS pattern
Vasculitic neuropathy	Mononeuritis multiplex; stepwise; systemic symptoms	ESR, CRP; nerve biopsy
Chemotherapy-induced neuropathy	Temporal relationship to chemo (platinum, taxanes, vincristine)	History
HIV neuropathy	Risk factors; CD4 count	HIV testing

6. MONITORING PARAMETERS

Parameter	ED	HOSP	OPD	ICU	Frequency	Target/Threshold	Action if Abnormal
HbA1c	-	ROUTINE	ROUTINE	-	q3 months until stable, then q6 months	<7% (individualized)	Intensify diabetes management
Foot exam (monofilament)	-	ROUTINE	ROUTINE	-	Every visit; comprehensive annually	Intact sensation	Podiatry; protective footwear
Symptom assessment (pain scores)	-	ROUTINE	ROUTINE	-	Every visit	NRS ≤3	Adjust pain medications
Renal function	-	ROUTINE	ROUTINE	-	Annually; more if on gabapentinoids	Stable eGFR	Dose adjust medications
B12 level	-	-	ROUTINE	-	Annually if on metformin	>400 pg/mL	Supplement
Orthostatic vitals	-	ROUTINE	ROUTINE	-	If CAN suspected; every visit	SBP drop <20 mmHg	Autonomic treatment
Fall risk assessment	-	ROUTINE	ROUTINE	-	Every visit	Low risk	PT; home safety evaluation

7. DISPOSITION CRITERIA

Disposition	Criteria
Outpatient management	Stable neuropathy; adequate pain control; no active ulcers
Admit to hospital	Severe uncontrolled pain; infected diabetic foot ulcer; diabetic amyotrophy with functional decline
ICU admission	Sepsis from foot infection; autonomic crisis
Neurology follow-up	q3-6 months during treatment optimization; annually when stable
Podiatry follow-up	q3 months if high-risk feet; annually if low-risk
Urgent follow-up	New weakness, new ulcer, worsening pain despite treatment

8. EVIDENCE & REFERENCES

Recommendation	Evidence Level	Source
Intensive glycemic control prevents/slows neuropathy	Class I, Level A	DCCT (DCCT Research Group, NEJM 1993); UKPDS 33 (Lancet 1998)
Duloxetine effective for painful DPN	Class I, Level A	Multiple RCTs; FDA-approved
Pregabalin effective for painful DPN	Class I, Level A	Multiple RCTs; FDA-approved
Gabapentin effective for painful DPN	Class I, Level B	Multiple RCTs
TCAs effective for painful DPN	Class I, Level B	Multiple RCTs
Capsaicin 8% patch effective for localized pain	Class I, Level A	Multiple RCTs; FDA-approved
Midodrine for orthostatic hypotension	Class I, Level A	Multiple RCTs
Annual foot screening reduces amputation risk	Class I, Level A	Multiple studies
Multifactorial risk reduction (lipids, BP, glucose) improves outcomes	Class I, Level B	Multiple studies

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NOTES

• Diabetic neuropathy is the most common cause of neuropathy in developed countries
• DSPN affects up to 50% of diabetic patients; often asymptomatic initially
• Early detection through annual screening (monofilament, tuning fork) is critical
• Glycemic control is the ONLY intervention proven to prevent DPN progression (especially Type 1)
• Multifactorial risk reduction (glucose, lipids, BP, weight) provides best outcomes
• Painful DPN: Start with duloxetine or pregabalin/gabapentin; combination therapy often needed
• Avoid opioids if possible due to dependence risk; use only for refractory cases
• Metformin-associated B12 deficiency is common; screen and supplement
• Cardiovascular autonomic neuropathy increases mortality risk; screen high-risk patients
• Diabetic amyotrophy is self-limited (months to years) but painful; immunotherapy controversial
• Foot care education and proper footwear are essential to prevent amputations
• Annual comprehensive foot exam for ALL diabetic patients

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CHANGE LOG

v1.0 (January 29, 2026) - Initial template creation - Comprehensive pain management algorithm (first, second, third-line) - Autonomic neuropathy treatment section - Diabetic amyotrophy (DLRPN) included - Foot care and ulcer prevention emphasized - Small fiber neuropathy assessment included