In:
European Journal of Endocrinology, Oxford University Press (OUP), Vol. 167, No. 6 ( 2012-12), p. 839-845
Abstract:
Long-term treatment with topiramate reduces body weight and improves insulin sensitivity in obese humans. Our aim was to evaluate the effect of topiramate treatment for 4 weeks on insulin sensitivity and secretion, independent of weight loss. Design Randomized, double-blind, crossover, placebo-controlled study. Methods Thirteen obese (BMI 36.6±1.3 kg/m 2 (mean± s.e.m .)), insulin-resistant (homeostasis model of assessment-insulin resistance 2.0±0.2) women received topiramate (T, maximum dose of 75 mg) and placebo (P) for 4 weeks, separated by a 4-week washout period. Insulin sensitivity and β-cell function were assessed using a two-step hyperinsulinemic euglycemic clamp with stable isotopes and a hyperglycemic clamp. Results Hepatic and peripheral insulin sensitivities were not affected by topiramate treatment (glucose disposal rate (step 1 (insulin infusion rate 10 mU/m 2 per min) T: 17.5±0.8 vs P: 18.5±1.0 μmol/kg LBM per min, t =1.016, P =0.33; step 2 (insulin infusion rate 40 mU/m 2 per min) T: 27.9±3.2 vs P: 28.8±1.9 μmol/kg LBM per min, t =0.418, P =0.68)). Subjects lost a small amount of weight during the topiramate period (T: −1.0±0.2 vs P: −0.1±0.2 kg, t =2842, P =0.15). There were no changes in body fat mass, blood pressure, and fasting glucose. β-Cell function was not affected by topiramate as evidenced by an unaltered area under the curve of early (0–10 min; T: 1929.6±265.7 vs P: 2024.7±333.6 pmol/l, t =−0.357, P =0.73) and late (80–120 min; T: 28 017.7±5029.9 vs P: 31 567.7±5376.2 pmol/l, t =−1.481, P =0.16) phase insulin levels during hyperglycemia. The use of topiramate was associated with significant side effects such as paresthesia, nausea, dizziness, and concentration problems. Conclusions Low-dose topiramate treatment for 4 weeks, relative to placebo, had no significant effect on insulin sensitivity in overweight/obese adult females without established diabetes.
Type of Medium:
Online Resource
ISSN:
0804-4643
,
1479-683X
Language:
Unknown
Publisher:
Oxford University Press (OUP)
Publication Date:
2012
detail.hit.zdb_id:
1485160-X
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