Natural Progression of Diabetic Peripheral Neuropathy in the Zenarestat Study Population
Article Figures & Tables
Tables
- Table 1—
Summary of baseline demographic characteristics of patients with mild-to-moderate DPN
Patient characteristic Placebo Zenarestat 600 mg/day Zenarestat 1,200 mg/day n 472 481 475 Men 276 (58.5) 293 (60.9) 303 (63.8) White 386 (81.8) 395 (82.1) 404 (85.1) Hispanic 30 (6.4) 33 (6.9) 29 (6.1) Black 37 (7.8) 29 (6) 25 (5.3) Age (years) 51.9 ± 10.3 52.9 ± 9.8 52.5 ± 9.7 Type 2 diabetes 376 (79.7) 399 (83) 386 (81.3) Duration of diabetes (years) 10.5 ± 9.4 (0.4–52.6) 10.4 ± 10.1 (0.4–60.8) 10.3 ± 9.3 (0.4–49) Alcohol use (no. drinks/week) 1.1 ± 2.7 (0–21) 1.3 ± 3.2 (0–24) 1.4 ± 3.6 (0–42) HbA1c (%) 7.7 ± 1.5 (4.8–11.7) 7.8 ± 1.7 (4–12) 7.8 ± 1.5 (4–12.4) ≤8% 275 (62) 284 (62) 284 (62) 6.7 ± 0.7 6.8 ± 0.8 6.9 ± 0.8 >8% 170 (38) 176 (38) 173 (38) 9.3 ± 0.9 9.6 ± 0.8 9.5 ± 1.1 Nerve conduction velocity (m/s)* n 471 481 475 Median forearm sensory 55.8 ± 4.5 (38.7–75) 55.8 ± 4.2 (42.3–69) 55.9 ± 4.1 (40.6–67) Peroneal motor 40.2 ± 4.7 (20–56) 40.3 ± 4.5 (16.7–51.3) 40.1 ± 4.8 (18.3–54.7) Sural sensory† 41.6 ± 5 (21–56) 41.6 ± 5 (29.7–58.3) 41.2 ± 5.2 (23–59) Amplitude (mV) Median sensory 471 481 475 22.7 ± 12.4 (3.1–71) 22.8 ± 11.8 (4.4–78.2) 22.5 ± 11.5 (2.4–66.1) Sural sensory 470 481 475 7.4 ± 4 (−6.9 to 22.5) 7.5 ± 4.2 (1.3–30) 7.5 ± 4 (1.5–26.2) F-wave latency (m/s) Median motor 470 481 473 29.1 ± 2.5 (22.9–36.5) 29.1 ± 2.5 (21.6–35.3) 29 ± 2.5 (21.9–35.4) Peroneal motor 402 404 416 54.6 ± 6.3 (39.4–76.9) 55.1 ± 6.3 (38.6–77.8) 55.1 ± 6.5 (38.8–81.8) QST (“just noticeable difference”)*‡ n 471 481 475 Cool thermal 14.2 ± 4.5 (4.7–25) 13.9 ± 4.7 (4.7–25) 14.2 ± 4.3 (5.9–25) Vibratory 19.3 ± 3.2 (7–25) 19.7 ± 3.1 (10.3–25) 19.5 ± 12.9 (7.8–25) Neuropathy scores/examination MDNS (part 1) (0–30 points) 454 470 465 7.5 ± 4.9 (0–30) 8.1 ± 5.2 (0–28) 7.6 ± 5 (0–28) Monofilament examination 10 g (0–4 points) 453 469 464 1.1 ± 1.3 (0–4) 1.1 ± 1.4 (0–4) 1.1 ± 1.3 (0–4) MNSI (part B) (0–6 points) 469 479 472 2.6 ± 1.6 (0–6) 2.7 ± 1.6 (0–6) 2.7 ± 1.6 (0–6) PNSS (part 2,3) (0–14 points) 441 448 442 3 ± 2.2 (0–14) 3.4 ± 2.1 (0–10) 3.1 ± 2.1 (0–12) - Table 2—
Summary of electrophysiologic changes from baseline at 12 months in placebo patients
Measure Baseline Change from baseline P (95% CI)* Nerve conduction velocity (ms)† Median forearm sensory 471 360 55.8 ± 4.5 −0.05 ± 3.4 0.7703 (−0.04 to 0.03) HbA1c ≤8% 275 216 56.7 ± 4.4 −0.13 ± 3.3 0.5582 (−0.57 to 0.31) HbA1c >8%, n 170 122 54.5 ± 4.4 −0.06 ± 3.7 0.8553 (−0.73 to 0.6) Peroneal motor 471 359 40.2 ± 4.7 −0.2 ± 2.2 0.0717 (−0.44 to 0.02) HbA1c ≤8% 275 216 40.8 ± 4.7 −0.2 ± 2.2 0.1992 (−0.49 to 0.10) HbA1c >8% 170 121 39.2 ± 4.6 −0.21 ± 2.1 0.2837 (−0.59 to 0.18) Sural sensory 471 357 41.6 ± 5 −0.65 ± 3.7 0.0008 (−1.04 to −0.27) HbA1c ≤8% 275 216 42.3 ± 5 −0.61 ± 3.7 0.0016 (−1.11 to −0.11) HbA1c >8% 170 119 40.6 ± 4.8 −0.68 ± 3.4 0.0324 (−1.3 to −0.06) Amplitude (μV) Median sensory 471 359 22.7 ± 12.4 −0.80 ± 4.86 0.0021 (−1.3 to −0.29) HbA1c ≤8% 275 216 23.1 ± 12.2 −0.59 ± 5.21 0.0983 (−1.29 to 0.11) HbA1c >8% 170 121 22 ± 12.8 −1.03 ± 4.42 0.0116 (−1.82 to −0.23) Sural sensory 470 355 7.4 ± 4 −0.30 ± 3.11 0.0686 (−0.63 to 0.02) HbA1c ≤8% 275 214 7.4 ± 3.9 −0.16 ± 2.66 0.3904 (−0.52 to 0.20) HbA1c >8% 170 119 7.4 ± 4.3 −0.44 ± 3.86 0.2194 (−1.14 to 0.26) F-wave latency (ms) Median motor 470 355 29.1 ± 2.5 0.18 ± 0.92 0.002 (0.09 to 0.28) HbA1c ≤8% 274 214 28.9 ± 2.5 0.18 ± 0.89 0.0041 (0.06 to 0.3) HbA1c >8% 170 119 29.4 ± 4.5 0.15 ± 0.97 0.0887 (−0.02 to 0.33) Peroneal motor 402 276 54.6 ± 6.3 0.30 ± 3.08 0.1113 (−0.07 to 0.66) HbA1c ≤8% 239 170 54.1 ± 6.2 0.48 ± 3.28 0.0588 (−0.02 to 0.97) HbA1c >8% 143 92 55 ± 63 0.15 ± 2.14 0.6133 (−0.44 to 0.74) - Table 3—
Summary of quantitative sensory changes from baseline at 12 months in placebo patients*
Measure Baseline Change from baseline P (95% CI)† Cool thermal 471 360 14.16 ± 4.52‡ 0.60 ± 3.25 0.0005 (0.27 to 0.94) HbA1c ≤8% 275 217 14.0 ± 4.4 0.4 ± 3.4 0.0844 (−0.05 to 0.85) HbA1c >8% 170 121 14.4 ± 4.7 1 ± 3.1 0.0007 (0.42 to 1.54) Vibratory 471 359 19.31 ± 3.21 0.07 ± 1.70 0.4692 (−0.11 to 0.24) HbA1c ≤8% 275 216 19.5 ± 3.1 −0.02 ± 1.6 0.8424 (−0.24 to 0.20) HbA1c >8% 170 121 19 ± 3.4 0.3 ± 1.8 0.1069 (−0.06 to 1.54) - Table 4—
Summary of changes from baseline in the zenarestat-treated patients
Measure Placebo Zenarestat 600 mg/day Zenarestat 1,200 mg/day n 472 481 475 Nerve conduction velocity (ms)* Median forearm sensory 360 371 324 −0.05 ± 3.4 0.8 ± 2.9‡ 0.8 ± 2.9‡ HbA1c ≤8% 216 218 194 −0.13 ± 3.3 0.62 ± 3 0.79 ± 2.9 HbA1c >8% 122 139 115 −0.06 ± 3.7 0.93 ± 2.7 1 ± 3 Peroneal motor 359 372 324 −0.21 ± 2.2 0.72 ± 2.3‡ 0.81 ± 2.1‡ HbA1c ≤8% 216 219 194 −0.20 ± 2.2 0.77 ± 2.4 0.71 ± 2 HbA1c >8% 121 139 115 −0.21 ± 2.1 0.66 ± 2.1 1.1 ± 2.1 Sural sensory† 357 371 324 −0.7 ± 3.7‡ 0.06 ± 4 −0.02 ± 4 HbA1c ≤8% 216 218 194 −0.61 ± 3.7 0.20 ± 3.9 0.29 ± 4.1 HbA1c >8% 119 139 115 −0.68 ± 3.4 −0.07 ± 4 0.54 ± 3.6 Amplitude (mV) Median sensory amplitude 359 371 324 −0.8 ± 4.9‡ −0.38 ± 4.5 −0.2 ± 4 HbA1c ≤8% 216 218 194 −0.59 ± 5.2 −0.12 ± 4.4 −0.03 ± 4 HbA1c >8% 119 139 115 −1.03 ± 4.4 −0.82 ± 4.7 −0.57 ± 4 Sural sensory amplitude 355 371 323 −0.3 ± 3.1 −0.44 ± 2.4‡ −0.59 ± 2.7‡ HbA1c ≤8% 214 218 194 −0.16 ± 2.7 −0.34 ± 2.4 −0.59 ± 2.7 HbA1c >8% 119 139 114 −0.44 ± 3.9 −0.53 ± 2.4 −0.40 ± 2.3 F-wave latency (ms) Median motor 355 370 320 0.2 ± 0.9‡ −0.06 ± 1 0.02 ± 1 HbA1c ≤8% 214 217§ 193 0.18 ± 0.9 0.10 ± 0.9 0.07 ± 1.0 HbA1c >8% 119 139 114 0.15 ± 1 −0.24 ± 1.0§ −0.06 ± 0.9 Peroneal motor 276 277 254 0.3 ± 3.1 −0.13 ± 2.9 −0.34 ± 2.9 HbA1c ≤8% 170 162 156 0.48 ± 3.3 −0.08 ± 3.2 −0.25 ± 2.8 HbA1c >8% 92 103 85 0.15 ± 2.9 −0.16 ± 2.1 −0.37 ± 3 QST (“just noticeable difference”)*‖ Cool thermal 360 373 327 0.6 ± 3.3‡ 0.6 ± 3.2‡ 0.5 ± 3‡ HbA1c ≤8% 217 220 196 0.40 ± 3.4 0.42 ± 3.2 0.20 ± 2.9§ HbA1c >8% 121 139 116 0.98 ± 3.1 0.99 ± 3.1 0.98 ± 3.2§ Vibration 359 374 326 0.07 ± 1.7 0.2 ± 1.7 0.3 ± 1.7‡ HbA1c ≤8% 216 221 196 −0.02 ± 1.6 0.14 ± 1.7 0.13 ± 1.6§ HbA1c >8% 121 139 115 0.27 ± 1.8 0.22 ± 1.6 0.54 ± 1.9§ Data are means ± SD.
- *
↵* No response values had a value imputed. See text for details.
- †
↵† Sural sensory nerve conduction was mandatory as entrance criteria.
- ‡
↵‡ Statistically significant change from baseline at P < 0.05.
- §
↵§ Statistically significant change from baseline between HbA1c strata at P < 0.05.
- ‖
↵‖ QST using Computer-Assisted Sensory Examination-IV.
In this Issue
May 2004, 27(5)
Natural Progression of Diabetic Peripheral Neuropathy in the Zenarestat Study Population
