Topiramate improves neurovascular function, epidermal nerve fiber morphology, and metabolism in patients with type 2 diabetes mellitus

Figures & data

Table 1 Baseline clinical and demographic data (n = 20)

Variable	Mean ± SEM
Age (years)	61.5 ± 1.3
Race (W:B:A)	16:3:1
Gender (male:female)	15:5
Height (inches)	70 ± 0.9
Weight (lbs)	228 ± 11.9
BMI (kg/m^2)	32.5 ± 1.2 (normal 18.5–24.9)
Waist circumference (inches)	44.5 ± 1.5
Systolic BP (mmHg)	142 ± 4.1 (goal <130 mmHg in diabetes)
Diastolic BP (mmHg)	81 ± 1.9 (goal <90 mmHg in diabetes)
Pulse (beats per minute)	81 ± 3.9
Fasting serum glucose (mg/dL)	135 ± 7.6 (normal <99)
HbA1c (%)	7.4 ± 0.3 (goal <7 in diabetes)
Total cholesterol mg/dL	175 ± 9.7 (normal <200)
LDL mg/dL	94 ± 7 (normal <100)
HDL mg/dL	46 ± 3 (normal male >40, female >50)
Triglyceride mg/dL	176 ± 27 (normal <150)
Total neuropathy score (scored bilaterally)	31.1 ± 15.5 (normal <6, severe >40)
Cool detection threshold	9 ± 2 (normal 3.0 ± 1.0°C)
Warm detection threshold	11 ± 1 (normal 7.8 ± 1.0°C)
Monofilament threshold	5 ± 0.1 (normal 3.9 ± 0.2 log g)
Vibration perception	5.4 ± 2 (normal 0)

Abbreviations: LDL, low-density lipoprotein; HDL, high-density lipoprotein; SEM, standard error of mean; HbA_1c, glycosylated hemoglobin.

Figure 1 A) Mean ± SE dendritic length (Microns) at 4 sites before and after 18 weeks of topiramate treatment. Significant differences (ANOVA) are shown. B) Mean ± SE nerve fiber density (Fibers/mm) in skin at different sites before and after 18 weeks of topiramate treatment. A significant change was only found in proximal leg.

Figure 2 A skin biopsy sample before and after treatment with topiramate shows an increase in the intraepidermal nerve fiber density (epidermis indicated by box at arrow) and dendritic length after treatment.

Table 2 Variables with significant changes from baseline to 18 weeks post-initiation of treatment with topiramate

Variable	Baseline (pre)	18 weeks (post)	Significance
Weight (lb)	228 ± 11.9	220 ± 12.3	P < 0.0001
BMI	32.5 ± 1.2	31.3 ± 1.3	P < 0.001
Diastolic BP (mmHg)	81 ± 1.9	71 ± 1.6	P < 0.0001
Systolic BP (mmHg)	143 ± 4.1	122 ± 3.1	P < 0.0001
HbA1c (%)	7.4 ± 0.31	6.8 ± 0.20	P < 0.0001
Total neuropathy score (normal <6, severe >40)	31.1 ± 15.5	21.0 ± 11.5	P = 0.0026
Touch threshold	2.7 ± 3.1	0.45 ± 1.4	P = 0.004
Prickling threshold	4.3 ± 2.1	2.1 ± 2.4	P = 0.0008
Vibration threshold	5.4 ± 2.3	4.4 ± 2.2	P = 0.039

Abbreviations: BMI, body mass index; BP, blood pressure; HbA_1c, hemoglobin A_1c.