The effects of valproate and topiramate use on serum insulin, leptin, neuropeptide Y and ghrelin levels in epileptic children

Çiçek, Nafiye Polat; Kamaşak, Tülay; Serin, Hepsen Mine; Ökten, Ayşenur; Alver, Ahmet; Cansu, Ali

doi:10.1016/j.seizure.2018.03.013

Cited by 18 publications

(13 citation statements)

References 27 publications

(30 reference statements)

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“…Adiponectin is a protein derived from fat cells that has an important regulatory effect on the insulin concentrations and glucose balance, regulating insulin sensitivity through a variety of mechanisms (79). Insulin resistance or increased insulin levels (5,(80)(81)(82)119), increased leptin levels (79,80), and decreased adiponectin levels (79,82,119,120) have been reported in VPA subjects in a number of studies.…”

Section: The Possible Mechanism Of Ir/ Hyperinsulinemia Caused By Vpamentioning

confidence: 99%

“…4) Due to its involvement in leptin and adiponectin signaling, the reduction of adiponectin is significantly related to IR (119,128,129), which can enhance insulin sensitivity by increasing fatty acid oxidation and inhibiting liver glucose production (82). High leptin levels are closely related to IR (80,129). 5) Some researchers believe that VPA will injure the liver and affect the metabolism of insulin in the liver, which can bring about an increase in insulin concentrations (81,130).…”

Section: The Possible Mechanism Of Ir/ Hyperinsulinemia Caused By Vpamentioning

confidence: 99%

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Research Progress on the Effect of Epilepsy and Antiseizure Medications on PCOS Through HPO Axis

Zhang

Wei

et al. 2021

Front. Endocrinol.

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Epilepsy is a common chronic neurological disease that manifests as recurrent seizures. The incidence and prevalence of epilepsy in women are slightly lower than those in men. Polycystic ovary syndrome (PCOS), a reproductive endocrine system disease, is a complication that women with epilepsy are susceptible to, and its total prevalence is 8%–13% in the female population and sometimes as high as 26% in female epilepsy patients. The rate of PCOS increased markedly in female patients who chose valproate (VPA), to 1.95 times higher than that of other drugs. In addition, patients receiving other anti-seizure medications (ASMs), such as lamotrigine (LTG), oxcarbazepine (OXC), and carbamazepine (CBZ), also have reproductive endocrine abnormalities. Some scholars believe that the increase in incidence is related not only to epilepsy itself but also to ASMs. Epileptiform discharges can affect the activity of the pulse generator and then interfere with the reproductive endocrine system by breaking the balance of the hypothalamic–pituitary–ovarian (HPO) axis. ASMs may also cause PCOS-like disorders of the reproductive endocrine system through the HPO axis. Moreover, other factors such as hormone metabolism and related signalling pathways also play a role in it.

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Section: The Possible Mechanism Of Ir/ Hyperinsulinemia Caused By Vpamentioning

confidence: 99%

Section: The Possible Mechanism Of Ir/ Hyperinsulinemia Caused By Vpamentioning

confidence: 99%

Research Progress on the Effect of Epilepsy and Antiseizure Medications on PCOS Through HPO Axis

Zhang

Wei

et al. 2021

Front. Endocrinol.

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“…Thus, the homeostasis of insulin signaling represents a critical factor and is an important therapeutic target. In addition, AEDs could result in the alteration of insulin homeostasis in patients with epilepsy [ 36 , 37 ]. Treatment with valproic acid, a broad-spectrum antiepileptic drug used for therapy of generalized and focal epilepsies, is associated with obesity and hyperinsulinemia.…”

Section: Discussionmentioning

confidence: 99%

Association between the Serum Coenzyme Q10 Level and Seizure Control in Patients with Drug-Resistant Epilepsy

et al. 2021

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Drug-resistant epilepsy (DRE) is a chronic neurological disorder with somatic impacts and increased risk of metabolic comorbidities. Oxidative stress might play an important role in metabolic effects and as a regulator of seizure control, while coenzyme Q10 (CoQ10) could improve insulin sensitivity through antioxidant effects. We aimed to investigate the association between CoQ10 level and clinical outcome, represented by the seizure frequency and quality of life, in DRE patients. DRE patients (N = 33) had significantly higher serum insulin levels and lower scores on the physical domain of the World Health Organization Quality of Life questionnaire (WHOQoL) than gender-age matched controls. The serum CoQ10 level (2910.4 ± 1163.7 ng/mL) was much higher in DRE patients than the normal range. Moreover, the serum CoQ10 level was significantly correlated with the seizure frequency (r = −0.412, p = 0.037) and insulin level (r = 0.409, p = 0.038). Based on stratification by insulin resistance (HOMA-IR > 2.4), the subgroup analysis showed that patients with a greater HOMA-IR had higher CoQ10 levels and lower seizure frequency, and had a significantly worse quality of life. In summary, CoQ10 could be a mediator involved in the mechanism of epilepsy and serve as a biomarker of the clinical outcome in DER patients.

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“…Valproate has multiple mechanisms of action, including γ-aminobutyric acid (GABA) potentiation, blocking of T-type calcium channels, and blocking of sodium channels. One of the most observed side effects in clinical practice of VPA treatment is weight gain [8,9]. The incidence of this side effect differs 10-70% in child population among authors in the published data [10,11].…”

Section: Introductionmentioning

confidence: 99%

Influence of sodium valproate treatment on body mass and insulin resistance parameters in children with epilepsy

et al. 2021

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Introduction/Objective. One of the main side-effects in patients undergoing valproic acid treatment is weight gain. Weight gain might be the reason for drug discontinuation, especially in adolescent girls, and it has to be considered also before introducing the drug. The main goal of our study is to investigate a possible influence of antiepileptic therapy with sodium valproate on weight and glucose homeostasis in pediatric patients with epilepsy. Methods. The investigation included a total of 49 healthy children with recently diagnosed epilepsy. We measured height, weight and serum 12-hour overnight fasting glucose and insulin level before initiation and after 6- and 12-month valproic acid treatment period. The BMI and HOMA indexes were calculated for each patient and correlated after the initiation of therapy and after 6 and 12 months of therapy. Results. We found that children significantly gained weight with statistical significance (p<0.01) even after 6 months of therapy with a significant glucose metabolism change and statistical difference in average serum glucose and insulin levels (p<0.05). Conclusion. Our results show that a 12-month treatment with valproic acid in children with epilepsy has a great impact on weight gain and glucose homeostasis and metabolism. We strongly recommend that all children with recently diagnosed epilepsy at the initiation of valproate therapy should be closely monitored on a 6-month basis. Consultation of nutritionist is advised especially in children with preexisting problem with body weight.

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The effects of valproate and topiramate use on serum insulin, leptin, neuropeptide Y and ghrelin levels in epileptic children

Abstract: Low blood sugar not being observed, even though insulin levels are high, after fasting and in the postprandial period in epileptic children receiving VPA is indicative of insulin resistance. The elevation in leptin and neuropeptide Y levels observed in the VPA group also suggest this.

Cited by 18 publications

References 27 publications

Research Progress on the Effect of Epilepsy and Antiseizure Medications on PCOS Through HPO Axis

Research Progress on the Effect of Epilepsy and Antiseizure Medications on PCOS Through HPO Axis

Association between the Serum Coenzyme Q10 Level and Seizure Control in Patients with Drug-Resistant Epilepsy

Influence of sodium valproate treatment on body mass and insulin resistance parameters in children with epilepsy

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