Burden of illness associated with painful diabetic peripheral neuropathy among adults seeking treatment in the US: results from a retrospective chart review and cross-sectional survey

Figures & data

Table 1 Demographic and clinical characteristics, overall and by average pain severity

Characteristic	Overall (n = 112)	Mild (0–3) (n = 22)	Moderate (4–6) (n = 57)	Severe (7–10) (n = 32)	Pvalue*
Age, years					0.0231
Mean (SD)	61.1 ± 12.13	66.9 ± 10.78	60.6 ± 12.25	57.8 ± 11.84
Gender, n (%)					0.0556
Male	53 (47.3)	14 (63.6)	28 (49.1)	10 (31.3)
Race, n (%)					0.0179
Missing	2 (1.8)	0 (0.0)	1 (1.8)	1 (3.1)
American Indian or Alaska Native	2 (1.8)	0 (0.0)	1 (1.8)	1 (3.1)
Asian	2 (1.8)	1 (4.5)	1 (1.8)	0 (0.0)
Black or African American	15 (13.4)	1 (4.5)	6 (10.5)	8 (25.0)
Native Hawaiian or other Pacific Islander	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
White	77 (68.8)	19 (86.4)	42 (73.7)	15 (46.9)
Multiracial	2 (1.8)	1 (4.5)	0 (0.0)	1 (3.1)
Other	12 (10.7)	0 (0.0)	6 (10.5)	6 (18.8)
Education level, n (%)					0.0089
Missing	3 (2.7)	0 (0.0)	1 (1.8)	2 (6.3)
Less than high school	22 (19.6)	0 (0.0)	12 (21.1)	9 (28.1)
High school and beyond	87 (77.7)	22 (100.0)	44 (77.2)	21 (65.6)
NeP prescription coverage, n (%)					0.5224
Missing	2 (1.8)	1 (4.5)	1 (1.8)	0 (0.0)
No	9 (8.0)	2 (9.1)	6 (10.5)	1 (3.1)
Yes	101 (90.2)	19 (86.4)	50 (87.7)	31 (96.9)
Duration of diabetes, n (%)					0.3052
6 months to 1 year	6 (5.4)	3 (13.6)	2 (3.5)	1 (3.1)
1 to 2 years	15 (13.4)	4 (18.2)	6 (10.5)	5 (15.6)
>2 years	91 (81.3)	15 (68.2)	49 (86.0)	26 (81.3)
Time since pDPN diagnosis, months
Mean (SD)	70.9 ± 65.28	81.8 ± 90.82	68.5 ± 50.96	69.2 ± 69.31	0.9003
Number of comorbid conditions^a					0.1441
Mean (SD)	3.1 ± 2.18	2.2 ± 1.11	3.0 ± 2.21	3.8 ± 2.40
Employment status, n (%)					0.0605
Missing	5 (4.5)	2 (9.1)	1 (1.8)	2 (6.3)
Employed for pay	20 (17.9)	4 (18.2)	10 (17.5)	6 (18.8)
Disabled	38 (33.9)	3 (13.6)	20 (35.1)	15 (46.9)
Retired	41 (36.6)	13 (59.1)	21 (36.8)	6 (18.8)
Unemployed	6 (5.4)	0 (0.0)	3 (5.3)	3 (9.4)
Other	2 (1.8)	0 (0.0)	2 (3.5)	0 (0.0)

Notes:

* P values are from the Kruskal–Wallis test for continuous variables; the Chi-square test for income level and health insurance; and the Fisher’s Exact test for the remaining categorical variables; mild versus moderate versus severe; ^aamong subjects with at least one comorbid condition. One subject did not respond to all required items needed to calculate a BPI average pain severity score and thus was not included in any analysis by pain severity category.

Abbreviations: BPI, Brief Pain Inventory; SD, standard deviation; pDPN, painful diabetic peripheral neuropathy; NeP, neuropathic pain.

Figure 1 Comorbidities among pDPN subjects, by average pain severity.*

Notes: *Scores on the BPI Pain Severity were used to classify average pain severity as follows: 0–3 represents mild pain, 4–6 represents moderate pain, and 7–10 represents severe pain; ^‡proportion of pDPN subjects with Headache/migraine significantly different by pain severity (P = 0.0001); ^†proportion of pDPN subjects with Chronic Low Back Pain significantly different by pain severity (P = 0.0027).

Table 2 Subject-reported outcomes, overall and by average pain severity

Scale	Overall (n = 112)	Mild (0–3) (n = 22)	Moderate (4–6) (n = 57)	Severe (7–10) (n = 32)	Pvalue*
SF-12^a
Physical functioning					0.0006
Mean (SD)	33.3 ± 32.60	58.0 ± 35.68	31.1 ± 30.72	21.1 ± 24.68
Median	25.0	50.0	25.0	25.0
Range	0–100	0–100	0–100	0–100
Role physical					0.0001
Mean (SD)	39.4 ± 28.53	62.5 ± 32.50	37.7 ± 23.08	27.3 ± 26.07
Median	37.5	62.5	37.5	25.0
Range	0–100	0–100	0–100	0–100
Bodily pain					<0.0001
Mean (SD)	40.2 ± 28.35	70.5 ± 26.32	39.5 ± 23.12	21.1 ± 20.19
Median	25.0	75.0	25.0	25.0
Range	0–100	25–100	0–100	0–75
General health					<0.0001
Mean (SD)	35.9 ± 24.56	61.6 ± 24.12	32.2 ± 20.44	25.3 ± 19.96
Median	25.0	60.0	25.0	25.0
Range	0–85	0–85	0–85	0–60
Vitality					0.0002
Mean (SD)	33.5 ± 26.11	51.1 ± 22.46	32.0 ± 23.51	23.4 ± 27.63
Median	25.0	50.0	25.0	25.0
Range	0–100	0–75	0–75	0–100
Social functioning					0.0003
Mean (SD)	56.5 ± 32.49	73.9 ± 26.14	60.1 ± 30.93	38.3 ± 31.74
Median	50.0	75.0	50.0	25.0
Range	0–100	25–100	0–100	0–100
Role emotional					<0.0001
Mean (SD)	58.4 ± 31.09	80.7 ± 23.38	62.5 ± 28.35	35.2 ± 26.27
Median	50.0	87.5	62.5	25.0
Range	0–100	13–100	0–100	0–100
Mental health					<0.0001
Mean (SD)	58.5 ± 23.32	72.7 ± 19.15	62.3 ± 21.32	41.4 ± 19.94
Median	62.5	81.3	62.5	50.0
Range	0–100	25–100	13–100	0–88
EQ-5D^a
Health state utility					<0.0001
Mean (SD)	0.61 ± 0.22	0.80 ± 0.13	0.66 ± 0.17	0.39 ± 0.18
Median	0.7	0.8	0.7	0.4
Range	0.2–1.0	0.4–1.0	0.2–0.8	0.2–0.8
HADS
HADS Anxiety, n (%)					0.0026
Normal (0–7)	48 (42.9)	16 (72.7)	25 (43.9)	7 (21.9)
Mild (7–10)	40 (35.7)	6 (27.3)	20 (35.1)	13 (40.6)
Moderate (11–14)	20 (17.9)	0 (0.0)	11 (19.3)	9 (28.1)
Severe (15–21)	4 (3.6)	0 (0.0)	1 (1.8)	3 (9.4)
HADS Depression, n (%)					0.0030
Normal (0–7)	63 (56.3)	18 (81.8)	33 (57.9)	12 (37.5)
Mild (7–10)	21 (18.8)	4 (18.2)	12 (21.1)	4 (12.5)
Moderate (11–14)	19 (17.0)	0 (0.0)	8 (14.0)	11 (34.4)
Severe (15–21)	9 (8.0)	0 (0.0)	4 (7.0)	5 (15.6)

Notes:

* P values are from the Kruskal–Wallis test for continuous variables; mild versus moderate versus severe. P values are from the Fisher’s Exact test for categorical variables; mild versus moderate versus severe; ^ahigher scores indicate a better subject-reported outcome.

Abbreviations: SD, standard deviation; EQ-5D, EuroQol 5-dimensions; HADS, Hamilton Anxiety and Depression Scale; SF-12, 12-Item Short-Form Health Survey; NeP, neuropathic pain.

Figure 2A SF-12 physical and mental component summary scores, overall and by average pain severity.*

Notes: *Scores on the BPI Pain Severity were used to classify average pain severity as follows: 0–3 represents mild pain, 4–6 represents moderate pain, and 7–10 represents severe pain; ^†P < 0.0001 for both PCS and MCS. All domains [physical function, role physical, bodily pain, general health, vitality, social functioning, role emotional, mental health] including PCS and MCS significantly different by average pain severity (P < 0.001).

Figure 2B Pain interference with function, overall and by average pain severity.*

Notes: *Scores on the BPI Pain Severity were used to classify average pain severity as follows: 0–3 represents mild pain, 4–6 represents moderate pain, and 7–10 represents severe pain; ^†P < 0.0001 for BPISF Pain Interference Index by pain severity. All domains [general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life] significantly different by average pain severity (P < 0.0001).

Figure 2C MOS-SS overall sleep index, overall and by average pain severity.*

Notes: *Scores on the BPI Pain Severity were used to classify average pain severity as follows: 0–3 represents mild pain, 4–6 represents moderate pain, and 7–10 represents severe pain; ^†P < 0.0001 for Overall Sleep Index by pain severity. All domains [sleep disturbance, sleep adequacy, sleep somnolence, snoring, shortness of breath or headache, sleep quantity] significantly different by average pain severity (P < 0.05).

Figure 3A Proportion of pDPN subjects taking prescription medications for pDPN, overall and by average pain severity.*

Notes: *Scores on the BPI Pain Severity were used to classify average pain severity as follows: 0–3 represents mild pain, 4–6 represents moderate pain, and 7–10 represents severe pain; ^†proportion of pDPN subjects taking prescription medications for their pDPN significantly different by pain severity (P = 0.0004).

Figure 3B Use of prescription treatments for pDPN, overall.*

Notes: *Subjects may be taking more than one class of prescription medication; ^†Weak SOA, Strong SAO, and LAO were also collapsed into “All Opioids” class; proportion prescribed = 33.0% overall, 9.1% mild, 31.6% moderate, 53.1% severe (P = 0.0027).
Abbreviations: AEDs, antiepileptics; SAO, strong-acting opioids; NSAIDs, nonsteroidal anti-inflammatory drugs; LAO, long-acting opioids; SNRIs, Serotonin–norepinephrine reuptake inhibitors; TCAs, tricyclic antidepressants; SSRI, selective serotonin re-uptake inhibitors.

Table 3 Resource utilization for painful diabetic peripheral neuropathy, overall and by average pain severity

Resource use	Overall (n = 112)	Mild (0–3) (n = 22)	Moderate (4–6) (n = 57)	Severe (7–10) (n = 32)	Pvalue*
Medication
Prescription medications prescribed to subject^a, mean (SD)	1.6 ± 1.25	0.9 ± 1.04	1.5 ± 1.10	2.2 ± 1.37	0.0004
Nonprescription medications used^b, mean (SD)	0.9 ± 1.24	0.7 ± 0.89	1.0 ± 1.41	0.9 ± 1.13	0.7325
Office visit^a
Physician office visits for NeP, mean (SD)	2.5 ± 1.86	1.7 ± 1.35	2.4 ± 1.59	3.3 ± 2.31	0.0171
Nonphysician office visits for NeP over the past 6 months, mean (SD)	0.1 ± 0.23	0.1 ± 0.29	0.1 ± 0.26	0.0 ± 0.00	0.2621
Test and procedure^a
Outpatient tests or procedures, mean (SD)	0.8 ± 1.92	1.0 ± 1.46	0.8 ± 2.13	0.5 ± 1.83	0.0143
ER visits for NeP^a, mean (SD)	0.0 ± 0.09	0.0 ± 0.00	0.0 ± 0.00	0.0 ± 0.18	0.2910
Hospital outpatient visits for NeP^a, mean (SD)	0.0 ± 0.00	0.0 ± 0.00	0.0 ± 0.00	0.0 ± 0.00	1.0000
Hospitalizations for NeP^a, mean (SD)	0.0 ± 0.00	0.0 ± 0.00	0.0 ± 0.00	0.0 ± 0.00	1.0000

Notes:

* P values are from the Kruskal–Wallis test for continuous variables and Fisher’s Exact test for categorical variables; mild versus moderate versus severe; ^aover the past 6 months; ^bover the past 4 weeks. One subject did not respond to all required items needed to calculate a BPI average pain severity score and thus was not included in any analysis by pain severity category.

Abbreviations: SD, standard deviation; ER, emergency room; NeP, neuropathic pain; BPI, Brief Pain Inventory.

Table 4 Subject-reported nonprescription medications used to treat painful diabetic peripheral neuropathy, overall and by average pain severity

Characteristic	Overall (n = 112)	Mild (0–3) (n = 22)	Moderate (4–6) (n = 57)	Severe (7–10) (n = 32)	Pvalue*
Nonprescription medication used in past 4 weeks					0.8217
n (%)^a
Missing	0 (0.0)	0 (0.0)	0 (0.0)	0 (0.0)
No	55 (49.1)	12 (54.5)	27 (47.4)	16 (50.0)
Yes	57 (50.9)	10 (45.5)	30 (52.6)	16 (50.0)
Nonprescription treatment used^b
Aspirin, n (%)	13 (11.6)	1 (4.5)	8 (14.0)	4 (12.5)	0.6942
Acetaminophen, n (%)	14 (12.5)	2 (9.1)	11 (19.3)	1 (3.1)	0.0869
Ibuprofen, n (%)	28 (25.0)	7 (31.8)	13 (22.8)	7 (21.9)	0.3053
Naproxen, n (%)	9 (8.0)	1 (4.5)	3 (5.3)	5 (15.6)	0.1571
Herbs, n (%)	5 (4.5)	0 (0.0)	3 (5.3)	2 (6.3)	0.8268
Vitamins, n (%)	20 (17.9)	2 (9.1)	13 (22.8)	5 (15.6)	0.5278
Supplements, n (%)	9 (8.0)	1 (4.5)	4 (7.0)	4 (12.5)	0.6048
Other, n (%)	7 (6.3)	1 (4.5)	4 (7.0)	2 (6.3)	1.0000

Notes:

* P values are from the Kruskal–Wallis test for continuous variables and the Fisher’s Exact test for categorical variables; mild versus moderate versus severe; ^atwo subjects who reported using a specific nonprescription medication were assumed to have answered “yes” to the question: “Have you taken any nonprescription (over-the-counter) medications (including pills, tablets, capsules, and/or topical lotions or creams), herbs, vitamins, and/or other supplements in the past 4 weeks for your neuropathic pain?”; ^bbecause more than one response may be selected, the sum of percentages across response options may exceed 100. Mild, moderate, and severe classification was based on the average BPI pain severity score. One subject did not respond to all required items needed to calculate an average BPI pain severity score and thus was not included in any analysis by pain severity category.

Abbreviation: BPI, Brief Pain Inventory.

Table 5 Work productivity and activity impairment: pDPN (WPAI:pDPN), overall and by average pain severity

Productivity	Overall (n = 112)	Mild (0–3) (n = 22)	Moderate (4–6) (n = 57)	Severe (7–10) (n = 32)	Pvalue*
Employed for pay, n (%)	20 (17.9)	4 (18.2)	10 (17.5)	6 (18.8)	1.0000
Overall work impairment^a,b					0.1721
n	19	3	10	6
Mean (SD)	43.6 ± 32.9	23.3 ± 5.8	36.4 ± 31.3	65.6 ± 34.6
Median	30.0	20.0	30.0	75.0
Range	0–100	20–30	0–100	0–100
Activity impairment^a					<0.0001
n	111	22	57	31
Mean (SD)	52.3 ± 31.1	21.4 ± 21.9	52.5 ± 27.7	74.8 ± 23.2
Median	60.0	15.0	60.0	80.0
Range	0–100	0–70	0–100	0–100

Notes:

* P values are from the Kruskal–Wallis test for continuous variables and the Fisher’s Exact test for categorical variables; mild versus moderate versus severe; ^ahigher values indicate greater impairment; ^bamong those employed for pay. One subject did not respond to all required items needed to calculate a BPI average pain severity score and thus was not included in any analysis by pain severity category.

Abbreviations: BPI, Brief Pain Inventory; SD, standard deviation; dDPN, painful diabetic peripheral neuropathy; WPAI, Work Productivity and Activity Impairment.

Figure 4 Adjusted average annualized cost per pDPN subject, overall and by average pain severity.*

Notes: *Scores on the BPI Pain Severity were used to classify average pain severity as follows: 0–3 represents mild pain, 4–6 represents moderate pain, and 7–10 represents severe pain; ^†average annualized total direct cost per pDPN subject was significantly different by pain severity (P < 0.0001). Direct costs include physician visits, other healthcare provider visits, prescription medications, TENS device, outpatient tests/procedures, emergency room visits, hospital outpatient visits, hospitalizations, direct medical costs to subjects, and direct non-medical (child care, help with house and/or yard work, and help with activities of daily living) due to pDPN; ^‡average annualized total indirect cost per pDPN subject was significantly different by pain severity (P = 0.0003). Total indirect costs include overall work impairment, activity impairment, disability, unemployment, early retirement, and reduced work schedule due to pDPN; ^§adjusted LS mean estimates from multiple linear regression adjusted for confounding demographic and clinical variables. Covariates included in adjusting direct costs: race, pain severity (mild/moderate/severe only), employment status, worker’s compensation, and comorbidities (depressive symptoms, headache/migraine, fibromyalgia [mild/moderate/severe only], chronic fatigue syndrome [overall only], and chronic low back pain); covariates included in adjusting indirect costs: sex, race, pain severity, employment status, worker’s compensation, and comorbidities (major depressive disorder and Raynaud’s syndrome).