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Online-Only appendix
Table A1. Clinical characteristics of the studied groups.
Controls(C) / Non-Neuropathic DM Patients
(DM) / Neuropathic DM Patients
(PDN)
No / 24 / 22 / 18
Age (years) / 57 ± 5 / 58 ± 11 / 54 ± 9
Males (%) / 10 (42%) / 12 (55%) / 12 (67%)
DM duration (years) / - / 12 ± 10 / 14 ± 14
BMI * / 26.2 ± 5.1 / 33.1 ± 6.2 / 32.8 ± 6.1
Systolic BP (mm Hg)¶ / 124 ± 14 / 127 ± 15 / 145 ± 16
Diastolic BP (mm Hg) / 72 ± 8 / 74 ± 10 / 75 ± 8
HbA1c † / 5.6 ± 0.2 / 7.3 ± 0.9 / 8.1 ± 2.1
Creatinine (mg/dl) § / 0.9 ± 0.2 / 0.9 ± 0.3 / 1.1 ± 0.3
Total Cholesterol (mg/dl) ‡ / 212 ± 31 / 169 ± 45 / 178 ± 29
HDL Cholesterol (mg/dl) / 66 ± 19 / 56 ± 21 / 48 ± 13
Neuropathy Symptom Score (NSS) ** / 0 ± 0 / 2 ± 3 / 3 ± 2
Neuropathy Disability Score (NDS) ¶¶ / 0 ± 0 / 1 ± 1 / 11 ± 6
Vibration Perception Threshold (VPT, volts) †† / 7 ± 2 / 12 ± 5 / 33 ± 17
Semmes-Weinstein Monofilaments§§ / 3.87 ± 0.50 / 4.04 ± 0.43 / 6.03 ± 0.88
Ankle Brachial Index (ABI) / 1.1 ± 0.1 / 1.1 ± 0.1 / 1.0 ± 0.2
Flow Mediated Vasodilation (FMD) (%)‡‡ / 8.8 ± 2.5 / 6.0 ± 1.6 / 5.2 ± 1.8
Nitroglycerin Induced Vasodilation (NID) (%) / 17.1 ± 2.3 / 15.9 ± 3.8 / 13.7 ± 8.6
Foot resting skin blood flow (Volts) / 1.0 ± 0.5 / 0.9 ± 0.4 / 1.2 ± 0.4
Foot Ach response (%) / 33 ± 24 / 45 ± 43 / 25 ± 25
Foot SNP response (%) / 35 ± 25 / 43 ± 34 / 27 ± 25
Mean ± SD
*: C vs DM, PDN: p <0.0001,
¶: C, DM vs PDN: p <0.0001,
†: C vs DM, PDN: p <0.0001,
§: C vs PDN: p <0.05.
‡: C vs DM, PDN: p <0.001,
&: C vs PDN: p <0.05,
**: C vs DM vs PDN: p <0.0001,
¶¶: C, DM vs PDN: p <0.0001,
††: C, DM vs PDN: p <0.0001,
§§: C, DM vs PDN: p <0.0001,
‡‡: C vs DM, PDN: p <0.0001,
&: C vs PDN: p<0.0001
Table A2.
Controls(C) / Non-Neuropathic DM Patients
(DM) / Neuropathic DM Patients
(PDN)
G-CSF(pg/ml) / 10.2 (8.0 : 14.9) / 9.4 (4.2 : 21.9) / 19.4 (12.9 : 23.8)
TNFa(pg/ml) * / 4.18 (2.92 : 6.33) / 4.84 (3.34 : 8.08) / 7.07 (5.32 : 9.66)
hCRP(μg/ml) ¶ / 2.54 (1.78 : 5.41) / 4.55 (1.52 : 21.70) / 7.17 (3.75 : 23.98)
VEGF(pg/ml) / 89 (21 : 204) / 78 (34 : 223) / 119 (64 : 269)
PDGF-AA(ng/ml) / 25.4 (20.0 : 35.0) / 25.7 (19.4 : 34.4) / 17.1 (10.2 : 34.8)
sE-Selectin(ng/ml) / 18.7 (13.4 : 31.5) / 23.5 (13.6 : 29.6) / 27.0 (18.4 : 46.5)
sICAM-1(ng/ml) / 89.7 (68.8 : 130.0) / 84.3 (75.2 : 107.5) / 100.2 (84.3 : 176.0)
sVCAM-1(ng/ml)† / 863 (587 : 1073) / 735 (603 : 903) / 1085 (903 : 1243)
Median, (first : third quartiles)
*: C vs PDN: p <0.05,
¶: C vs PDN: p <0.05,
†: C, DM vs PDN: p <0.02
Figure A1.Representative T1-weighted (T1W) (left column) and PCr/Pi (right column) images at the metatarsal head region of the foot, acquired from a normal control subject (top row), a diabetic patient without neuropathy (middle row), and a neuropathic patient (bottom row). In the PCr/Pi images only the muscle tissue is seen since the concentrations of 31P compounds in fat, bone and connective tissues is too low to detect using MR methods. The T1W image of the normal control subject (a) indicates little inter-muscular fat (bright regions) infiltrating the muscle (dark gray regions). Slightly more inter-muscular fat appears in the T1W image of the non-neuropathic patient (c) and a substantial amount of inter-muscular fat can be seen in the T1W image of the neuropathic patient’s foot (e). The PCr/Pi of the normal control subject (b) lies in the high range (blue to red). In the non-neuropathic patient (d), regions containing lower levels of PCr/Pi appear (indigo to violet) while fewer and smaller regions of higher PCr/Pi (green to red) are present compared to the normal control subject. The cross-section of the neuropathic patient (f) has still larger regions of muscle containing low PCr/Pi and fewer regions containing high PCr/Pi. There is also less muscle area visible in f due to muscle atrophy and fatty infiltration. The average PCr/Pi across the entire cross-sections of the normal control subject, non-neuropathic patient and the neuropathic patient are, 3.45, 2.68 and 1.81, respectively.
Figure A1