Dept. of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
School of Artificial intelligence, Bennett University, Greater Noida, UP, India.
Seizure. 2024 Oct;121:123-132. doi: 10.1016/j.seizure.2024.08.003. Epub 2024 Aug 3.
To evaluate the incidence of insulin resistance and its association with change in serum anti-seizure medication (ASM) level and their pharmacokinetic, body composition and metabolic hormones after six months of levetiracetam (LEV) exposure in persons with epilepsy (PWE) in comparison to valproate (VPA).
This prospective-longitudinal study included clinically diagnosed PWE on VPA or LEV monotherapy (for<3 months). At enrolment, body weight/composition, BMI were measured and blood samples were collected for assessing metabolic dysfunctions by estimation of serum insulin, insulin resistance [in terms of Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)], leptin, adiponectin, lipid profile along with ASMs level. Subjects were followed up for six months and all the above parameters were reassessed.
A total of 150 PWE were screened based on inclusion and exclusion criteria, and 105 number of subjects were enrolled (n = 35 in VPA and n = 70 in LEV group). Out of them, 92 subjects (n = 32 in VPA; n = 60 in LEV) completed six months follow-up. After six months, serum insulin level increased significantly in VPA group compared to baseline p < 0.001). Insulin resistance (HOMA-IR>2.5) was observed in 14.28 % of PWE in VPA group. Significantly higher percentage-change in body-weight (p = 0.003), leptin and decreased adiponectin were found in VPA-group compared to baseline ((p = 0.003, 0.02, 0.001, <0.001, respectively). These changes were independent of serum level or pharmacokinetic of VPA. On the other hand, no such changes were observed in LEV-group despite increased serum LEV level and altered pharmacokinetic parameters after six months.
Six months treatment with VPA resulted in insulin resistance and metabolic dysfunctions in PWE. These alterations were not correlated with change in VPA serum level. These changes were not observed in LEV therapy suggesting its better safety profile. This may be considered while prescribing the ASM like VPA and LEV in adult patients with obesity or insulin resistance and diabetes.
评估癫痫患者（PWE）在使用左乙拉西坦（LEV）治疗六个月后，与丙戊酸钠（VPA）相比，胰岛素抵抗的发生率及其与血清抗癫痫药物（ASM）水平变化的相关性，以及其药代动力学、身体成分和代谢激素的变化。
本前瞻性纵向研究纳入了临床诊断为 VPA 或 LEV 单药治疗（<3 个月）的 PWE。入组时，测量体重/成分、BMI，并采集血样，通过测定血清胰岛素、胰岛素抵抗[稳态模型评估的胰岛素抵抗（HOMA-IR）]、瘦素、脂联素、血脂谱以及 ASM 水平来评估代谢功能障碍。对患者进行了六个月的随访，并重新评估了所有上述参数。
根据纳入和排除标准，共筛选了 150 名 PWE，其中 105 名患者入组（VPA 组 35 名，LEV 组 70 名）。其中，92 名患者（VPA 组 32 名，LEV 组 60 名）完成了六个月的随访。六个月后，VPA 组血清胰岛素水平较基线显著升高（p<0.001）。VPA 组有 14.28%的 PWE 出现胰岛素抵抗（HOMA-IR>2.5）。与基线相比，VPA 组的体重（p=0.003）、瘦素显著增加，脂联素显著降低（p=0.003、0.02、0.001、<0.001，分别）。这些变化与 VPA 的血清水平或药代动力学无关。另一方面，在 LEV 组中，尽管六个月后血清 LEV 水平升高和药代动力学参数改变，但未观察到这些变化。
VPA 治疗六个月后，PWE 出现胰岛素抵抗和代谢功能障碍。这些改变与 VPA 血清水平的变化无关。在 LEV 治疗中未观察到这些变化，表明其安全性更好。在为肥胖或胰岛素抵抗和糖尿病的成年患者开具 VPA 和 LEV 等 ASM 时，可以考虑这些因素。
