Table 1 Comparing normal IENFD between different sexes
Biopsy area
|
Male
(n=18)
|
Female
(n=16)
|
t
|
P
|
Distal thigh
|
21.5±5.5
|
20.0±6.8
|
0.457
|
0.478
|
Proximal thigh
|
11.0±3.1
|
11.6±4.6
|
-0.229
|
0.733
|
Table 2 Comparing the normal IENFD between different ages
Biopsy area
|
20~50 years
(n=13)
|
51~80 years
(n=21)
|
t
|
P
|
Distal thigh
|
19.0±5.9
|
21.5±6.2
|
-0.731
|
0.478
|
Proximal thigh
|
11.9±4.3
|
10.4±2.4
|
0.533
|
0.617
|
Table 3 Demographic indexes of subjects participating in the skin biopsy
|
Non-DPN
(n=7)
|
Pure SFN
(n=37)
|
Mixed DPN
(n=45)
|
P
|
Age (years)
|
55.7±14.6
|
57.6±10.2
|
57.4±11.4
|
0.925
|
Sex (male, %)
|
42.9 (3)
|
59.5 (22)
|
64.4 (29)
|
0.543
|
BMI (kg/m2)
|
23.2±3.0
|
24.1±3.2
|
23.8±3.3
|
0.775
|
SBP (mmHg)
|
103.0±9.9
|
121.7±13.5
|
129.6±16.6
|
0.027b
|
DBP (mmHg)
|
60.7±1.2
|
71.9±9.9
|
77.4±13.0
|
0.025b
|
Resting heart rate (bpm)
|
64.7±2.9
|
70.4±9.6
|
75.4±10.6
|
0.039b
|
Duration (years)
|
6.5 (3.0, 15.5)
|
10.0 (6.0, 16.3)
|
10.0 (4.5, 17.0)
|
0.491
|
Family history of diabetes (%)
|
42.9
|
54.1
|
53.3
|
0.858
|
Smoking (%)
|
0
|
40.5
|
33.3
|
0.114
|
Alcohol intake (%)
|
0
|
16.2
|
22.2
|
0.339
|
a: Pure SFN vs. Non-DPN, P≤0.05; b: Mixed DPN vs. Non-DPN, P≤0.05; c: Pure SFN vs. Mixed DPN, P≤0.05
Table 4 Biochemical indexes of subjects participating in the skin biopsy
|
Non-DPN
(n=7)
|
Pure SFN
(n=37)
|
Mixed DPN
(n=45)
|
P
|
HbA1C (%)
|
7.8 (6.4, 11.9)
|
7.0 (6.3, 9.6)
|
9.5 (7.3, 10.8)
|
0.005c
|
Fasting glucose (mmol/L)
|
7.9 (6.0, 9.6)
|
6.6 (5.5, 8.6)
|
7.8 (5.8, 9.8)
|
0.220
|
Fasting CP (pmol/L)
|
520.8 (371.9, 705.3)
|
577.1 (306.1, 779.6)
|
435.3 (215.0, 732.2)
|
0.398
|
Fasting insulin (μIU/ml)
|
6.7 (5.3, 8.9)
|
7.1 (3.7, 11.1)
|
6.2 (2.9, 9.4)
|
0.733
|
PBG (mmol/L)
|
15.3 (11.7, 17.6)
|
12.4 (9.8, 14.9)
|
15.6 (11.1, 18.5)
|
0.041c
|
PCP (pmol/L)
|
2425.0 (1310.0, 3446.3)
|
1374.0 (860.8, 2459.5)
|
966.7 (576.8, 1352.0)
|
0.001bc
|
PINS (μIU/ml)
|
36.8 (13.2, 51.8)
|
32.5 (9.6, 50.0)
|
13.4 (7.3, 26.4)
|
0.019c
|
HOMA-IR
|
2.5 (1.6, 3.4)
|
2.3 (0.9, 3.3)
|
2.1 (1.2, 4.0)
|
0.853
|
Lipid profiles (mmol/L)
|
|
|
|
|
TG
|
0.87 (0.6, 1.2)
|
1.2 (0.8, 1.7)
|
1.2 (0.9, 1.9)
|
0.155
|
TC
|
3.2 (2.3, 4.6)
|
4.2 (3.5, 4.8)
|
4.3 (3.7, 5.1)
|
0.197
|
HDL-C
|
1.3 (1.2, 1.8)
|
1.1 (0.9, 1.4)
|
1.2 (0.9, 1.4)
|
0.155
|
LDL-C
|
1.5 (0.7, 2.5)
|
2.3 (2.0, 2.9)
|
2.4 (2.0, 3.2)
|
0.159
|
eGFR (mL/min/1.73 m2)
|
128.2±18.5
|
121.3±28.0
|
112.9±35.3
|
0.345
|
ACR
|
7.4 (6.3, 14.4)
|
23.2 (11.4, 46.4)
|
34.3 (12.4, 157.2)
|
0.016b
|
Folate (ng/mL)
|
19.9 (13.2, 23.2)
|
16.1 (10.8, 22.4)
|
18.8 (14.2, 21.7)
|
0.575
|
Vitamin B12 (pg/ml)
|
599.9 (440.3, 632.3)
|
513.0 (409.6, 822.1)
|
694.8 (442.6, 1671.9)
|
0.426
|
25-OHD (ng/ml)
|
29.7 (25.2, 33.9)
|
19.4 (15.4, 26.1)
|
19.0 (10.2, 24.1)
|
0.014b
|
a: Pure SFN vs. Non-DPN, P≤0.05; b: Mixed DPN, vs. Non-DPN, P≤0.05; c: Pure SFN vs. Mixed DPN, P≤0.05
Table 5 Neurological indexes of subjects participating in the skin biopsy
|
Non-DPN
(n=7)
|
Pure SFN
(n=37)
|
Mixed DPN
(n=45)
|
P
|
IENFD of the proximal leg (/mm)
|
11.1 (8.9, 11.4)
|
2.3 (1.0, 4.9)
|
3.0 (1.2, 4.0)
|
0.004ab
|
IENFD of the distal leg (/mm)
|
15.8 (14.0, 18.0)
|
7.0 (3.4, 9.9)
|
4.5 (3.0, 7.0)
|
0.000ab
|
NSS
|
4.0 (3.8, 7.5)
|
5.0 (4.0, 7.0)
|
7.0 (4.3, 9.0)
|
0.119
|
NPRS
|
0.5 (0, 2.3)
|
0 (0, 3.0)
|
1.0 (0, 5.8)
|
0.533
|
CAN (%)
|
28.6
|
33.3
|
75
|
0.003bc
|
CART score
|
1.0 (1.0, 2.5)
|
1.5 (1.1, 2.0)
|
2.5 (1.0, 3.0)
|
0.023c
|
Postural BP change (mmHg)
|
7.5 (-7.0, 10.5)
|
3.0 (-6.0, 13.0)
|
12 (4, 21)
|
0.023c
|
Deep breathing max-min (bpm)
|
11.7 (6.9, 13.5)
|
8.8 (4.7, 15.2)
|
5.9 (4.0, 8.5)
|
0.040bc
|
Valsalva ratio
|
1.13 (1.06, 1.19)
|
1.16 (1.13, 1.29)
|
1.12 (1.08, 1.23)
|
0.076
|
30:15 ratio
|
1.02 (1.00, 1.07)
|
1.05 (0.96, 1.07)
|
1.00 (1.00, 1.05)
|
0.582
|
Average hands ESC (μS)
|
76.0 (70.9, 86.4)
|
64.5 (46.5, 74.0)
|
58.5 (44.5, 69.5)
|
0.056
|
Average feet ESC (μS)
|
85.8 (74.4, 90.4)
|
72.0 (65.0, 80.5)
|
70.5 (45.0, 80.0)
|
0.056
|
MCV of common peroneal nerve (ms)
|
44.1±4.4
|
43.7±4.1
|
38.3±5.1
|
0.000bc
|
MCV of tibial nerve (ms)
|
42.7±3.4
|
43.9±4.4
|
38.8±4.9
|
0.000c
|
a: Pure SFN vs. Non-DPN, P≤0.05; b: Mixed DPN vs. Non-DPN, P≤0.05; c: Pure SFN vs. Mixed DPN, P≤0.05
Table 6 Spearman correlations and the partial correlations between IENFD and related clinical indexes
Control Variables
|
|
|
IENFD-
proximal
|
IENFD- distal
|
Control variables
|
IENFD-
proximal
|
IENFD- distal
|
Control variables
|
IENFD-
proximal
|
IENFD- distal
|
None
|
SBP
|
r
|
-0.244
|
-0.256
|
Adjusted for age
|
-0.213
|
-0.332
|
Adjusted for age and duration
|
-0.241
|
-0.298
|
|
|
P
|
0.062
|
0.045*
|
|
0.205
|
0.045*
|
|
0.157
|
0.077
|
|
DBP
|
r
|
-0.231
|
-0.090
|
|
-0.092
|
-0.149
|
|
-0.117
|
-0.102
|
|
|
P
|
0.073
|
0.484
|
|
0.589
|
0.380
|
|
0.495
|
0.555
|
|
RHR
|
r
|
-0.160
|
-0.010
|
|
-0.101
|
0.178
|
|
-0.097
|
0.172
|
|
|
P
|
0.218
|
0.939
|
|
0.550
|
0.293
|
|
0.575
|
0.316
|
|
CART score
|
r
|
-0.182
|
-0.385
|
|
-0.128
|
-0.473
|
|
-0.121
|
-0.513
|
|
|
P
|
0.172
|
0.002**
|
|
0.452
|
0.003**
|
|
0.482
|
0.001**
|
|
HbA1c
|
r
|
0.065
|
0.064
|
|
0.145
|
0.053
|
|
0.331
|
0.954
|
|
|
P
|
0.559
|
0.563
|
|
0.392
|
0.754
|
|
0.188
|
0.342
|
|
PBG
|
r
|
0.066
|
-0.021
|
|
-0.108
|
-0.217
|
|
-0.126
|
-0.189
|
|
|
P
|
0.590
|
0.857
|
|
0.526
|
0.197
|
|
0.464
|
0.271
|
|
PCP
|
r
|
-0.022
|
0.025
|
|
-0.120
|
-0.057
|
|
-0.168
|
0.036
|
|
|
P
|
0.847
|
0.820
|
|
0.479
|
0.738
|
|
0.326
|
0.835
|
|
PINS
|
r
|
-0.021
|
-0.026
|
|
-0.020
|
-0.033
|
|
-0.008
|
-0.062
|
|
|
P
|
0.866
|
0.829
|
|
0.908
|
0.848
|
|
0.962
|
0.719
|
|
ACR
|
r
|
-0.256
|
-0.247
|
|
-0.111
|
-0.179
|
|
-0.128
|
-0.153
|
|
|
P
|
0.023*
|
0.024*
|
|
0.513
|
0.288
|
|
0.458
|
0.373
|
|
25-OHD
|
r
|
0.074
|
0.179
|
|
-0.031
|
0.009
|
|
-0.023
|
-0.010
|
|
|
P
|
0.504
|
0.097
|
|
0.856
|
0.958
|
|
0.894
|
0.954
|
*P≤0.05, **P≤0.01
Table 7 Biochemical and neurological indexes of pure SFN and mixed DPN subjects during the follow-up
|
Pure SFN (n=17)
|
Mixed DPN (n=9)
|
P1
|
P2
|
|
At initial visit
|
At final visit
|
At initial visit
|
At final visit
|
|
|
HbA1C (%)
|
6.7 (6.1, 8.5)
|
6.8 (6.2, 7.5)
|
10.2 (8.3, 10.5)
|
7.9 (6.8, 10.5)
|
0.600
|
0.236
|
Fasting glucose (mmol/L)
|
7.1 (5.5, 8.2)
|
6.4 (5.3, 7.5)
|
7.0 (5.8, 8.4)
|
6.4 (5.5, 9.4)
|
0.552
|
0.953
|
Fasting CP (pmol/L)
|
731.2 (460.0, 851.2)
|
528.0 (421.5, 688.0)
|
277.7 (143.8, 638.4)
|
407.0 (209.6, 527.6)
|
0.433
|
0.091
|
Fasting insulin (μIU/ml)
|
8.5 (4.4, 12.4)
|
6.0 (3.1, 9.9)
|
6.9 (2.2, 21.2)
|
10.2 (2.7, 32.5)
|
0.182
|
0.310
|
PBG (mmol/L)
|
12.4 (9.6, 13.7)
|
11.0 (9.0, 15.1)
|
13.7 (7.7, 17.7)
|
11.8 (10.8, 15.1)
|
0.224
|
0.866
|
PCP (pmol/L)
|
1540.0 (1331.3, 2766.0)
|
1798.0 (1483.5, 2272.0)
|
966.7 (482.9, 1430.5)
|
917.8 (524.6, 1510.5)
|
0.203
|
0.594
|
PINS (μIU/ml)
|
32.5 (13.9, 42.9)
|
36.8 (21.1, 57.8)
|
20.8 (7.9, 25.0)
|
15.9 (9.6, 65.4)
|
0.071
|
0.735
|
HOMA-IR
|
2.2 (0.9, 3.5)
|
1.5 (0.7, 2.9)
|
2.1 (0.8, 4.7)
|
3.2 (1.2, 9.3)
|
0.328
|
0.237
|
Lipid profiles (mmol/L)
|
|
|
|
|
|
|
TG
|
1.2 (0.7, 1.6)
|
1.3 (0.7, 1.8)
|
1.3 (0.8, 1.6)
|
1.1 (0.6, 1.7)
|
0.975
|
0.314
|
TC
|
4.5 (4.0, 4.9)
|
4.3 (3.6, 4.9)
|
4.3 (3.6, 4.4)
|
3.8 (3.3, 4.4)
|
0.133
|
0.515
|
HDL-C
|
1.2 (0.9, 1.5)
|
1.3 (0.9, 1.5)
|
1.4 (1.0, 1.6)
|
1.2 (1.1, 1.5)
|
1.00
|
0.635
|
LDL-C
|
2.6 (2.2, 2.8)
|
2.3 (1.9, 2.9)
|
2.4 (1.8, 2.7)
|
2.2 (1.6, 2.5)
|
0.363
|
0.374
|
eGFR (mL/min/1.73 m2)
|
128.0±20.0
|
131.8±23.7
|
106.6±27.1
|
108.5±64.3
|
0.599
|
0.917
|
ACR
|
27.7 (14.9, 57.5)
|
21.9 (4.7, 39.2)
|
34.0 (11.6, 103.6)
|
26.1 (11.1, 238.1)
|
0.972
|
0.091
|
Folate (ng/mL)
|
12.4 (9.9, 19.8)
|
12.5 (8.5, 17.5)
|
19.1 (15.1, 22.8)
|
12.6 (9.2, 18.6)
|
0.237
|
0.285
|
Vitamin B12 (pg/ml)
|
438.9 (391.0, 736.0)
|
599.0 (524.8, 1502.3)
|
771.0 (524.6, 2000.0)
|
497.0 (428.5, 636.9)
|
0.028*
|
0.068
|
25-OHD (ng/ml)
|
19.1 (14.9, 26.9)
|
29.1 (24.2, 32.9)
|
17.9 (9.7, 21.9)
|
13.3 (12.8, 24.7)
|
0.131
|
0.674
|
NSS
|
5.0 (4.0, 7.0)
|
4.0 (2.0, 5.0)
|
7.5 (4.5, 9.0)
|
8.0 (6.0, 9.0)
|
0.713
|
0.593
|
NPRS
|
1.5 (0, 4.5)
|
1.0 (0, 4.0)
|
2.0 (0, 6.5)
|
5.0 (3.0, 6.0)
|
0.583
|
0.414
|
CART score
|
1.5 (1.0, 2.0)
|
2.0 (0.5, 3.0)
|
2.8 (2.1, 3.6)
|
2.0 (2.0, 2.8)
|
0.892
|
0.461
|
Average hands ESC (μS)
|
57.8 (48.8, 74.5)
|
57.3 (48.0, 65.5)
|
48.0 (15.5, 71.3)
|
56.5 (22.5, 65.5)
|
0.515
|
1.000
|
Average feet ESC (μS)
|
71.8 (64.0, 77.3)
|
65.8 (54.5, 70.4)
|
54.0 (16.1, 79.0)
|
63.0 (13.5, 70.5)
|
0.260
|
0.176
|
MCV of common peroneal nerve (ms)
|
43.1±4.7
|
46.0±2.4
|
41.0±2.2
|
35.4±1.4
|
0.045*
|
0.025*
|
MCV of tibial nerve (ms)
|
43.4±6.0
|
46.9±4.0
|
36.6±3.1
|
34.2±1.4
|
0.093
|
0.047*
|
P1: Pure SFN at the initial visit vs. at the final visit; P2: Mixed SFN at the initial visit vs. at the final visit; *P≤0.05