Biochemical derangements related to metabolic syndrome in epileptic patients on treatment with valproic acid

Yadav, Nisha; Bobby, Zachariah; Wadwekar, Vaibhav

doi:10.1016/j.seizure.2018.06.003

Cited by 24 publications

(24 citation statements)

References 23 publications

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“…In our study, the HsCRP of both participated cases and controls was measured to evaluate possible in ammatory effects of AEDs, but our ndings showed that there was no signi cant difference in the levels of HsCRP between the VPA-treated group, the CBZ-treated group, and the controls. Although our result was supported by Nisha et al [48] Using the various indexes for evaluation of MetS and IR in epileptic patients is the strength of our study which is more than in other published studies. This study has some limitations, including limited sample size, lack of information on patients' MetS components before taking AEDs and also unmatched age of CBZ-treated and VPA-treated cases which was due to the nature of study in which CBZ usually should be prescribed for adult epileptics with partial epilepsy and VPA for younger subjects with generalized epilepsy.…”

Section: Discussionsupporting

confidence: 79%

“…On the other hand, CBZ therapy showed signi cant correlation with IR risk based on HOMA index only. Most studies have used the HOMA index, and they have reported signi cantly increased values of IR in VPA-treated cases [1,2,36,48]. However, Naja et al [19] studied the VPA-treated Iranian patients and they reported that there were normal values of insulin and no evidence of IR in VPA-treated as case and CBZ -treated as controls and this nding has also been supported by a study conducted by Kwan et al [49].…”

Section: Discussionmentioning

confidence: 85%

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Frequency of metabolic syndrome and insulin resistance in epileptic patients treated with sodium valproate or carbamazepine monotherapy: A Case-Control Study

Bayat¹,

Jalali²,

Poursadeghfard³

et al. 2021

Preprint

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Background Metabolic syndrome (MetS) represents a collection of metabolic risk factors such as obesity, dyslipidemia, hyperglycemia, and hypertension. Medications can increase the incidence rate of MetS and insulin resistance (IR). Objective This study aims to evaluate the effects of Carbamazepine (CBZ) or Valproate (VPA) as monotherapy on the development of MetS and IR in the adult Iranian epileptic patients. Methods In this observational analytic case-control study, 80 epileptic patients were treated with VPA (40 patients) or CBZ (40 patients) monotherapies for more than 6 months and 45 age and sex matched controls were included. MetS was assessed based on International Diabetes Federation (IDF) and National Cholesterol Education Program (NCEP) criteria. Results In the multiple regression analysis, in VPA-treated patients the risk of MetS (by IDF criteria) was increased 19 times higher than controls (OR = 19.20; 95% CI = 2.62-140.23, P = 0. 004) and risk of IR (by HOMA and QUICKI) was increased 15 and 9 times more than controls (OR = 14.83; 95% CI = 3.03–72.56, P = 0.001) and (OR = 9.13; 95% CI = 2.55–32.65, P = 0.001) respectively. Increase in waist, DBP, and insulin level were also showed as important factors in risk of MetS. In CBZ therapy, the risk of MetS (by IDF) depressed by 17% less than controls and the risk of IR (by HOMA) increased 7 times more than controls. Conclusion Treatment with VPA can increase the likelihood of developing MetS and IR while, CBZ therapy could decrease the risk of MetS and increase risk of IR in the epileptic patients in Iran compared to the general population.

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Section: Discussionsupporting

confidence: 79%

Section: Discussionmentioning

confidence: 85%

Frequency of metabolic syndrome and insulin resistance in epileptic patients treated with sodium valproate or carbamazepine monotherapy: A Case-Control Study

Bayat¹,

Jalali²,

Poursadeghfard³

et al. 2021

Preprint

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“…Similarly, treatment with VPA predisposed obese children with idiopathic epilepsy to insulin resistance and lower adiponectin levels compared to age and gender matched obese controls [88]. VPA also induced hypoadiponectinemia and insulin resistance in previously untreated people with epilepsy [89,90]. Other studies, however, have found non-significant increases in adiponectin levels after VPA treatment [91,92].…”

Section: 6mentioning

confidence: 99%

“…Proposed Mechanisms for Development of T2DM in People with Epilepsy One possible mechanism that we propose for the development of T2DM in people with epilepsy is that mitochondrial dysfunction [63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79] and adiponectin deficiency [83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102] predispose people to epilepsy, obesity, and diabetes. The same biological drivers underlie each of these three conditions due to the systemic nature of both these drivers and the conditions.…”

Section: 7mentioning

confidence: 99%

Drivers for the comorbidity of type 2 diabetes mellitus and epilepsy: A scoping review

Shlobin

Sander

2020

Epilepsy & Behavior

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Epilepsy, a common neurologic condition, is associated with a greater prevalence of type 2 diabetes mellitus (T2DM). We examined potential drivers for the comorbidity of epilepsy and T2DM in an attempt to elucidate possible biological mechanisms underlying the development of processes in individuals. We searched PubMed and Medline up to December 2019. Our search yielded 3,361 articles, of which 82 were included in the scoping review. We reviewed articles with a focus on the association of epilepsy and T2DM, drivers, and biological mechanisms. Epilepsy is associated with obesity and obesity is associated with T2DM. Treatment with valproate (either sodium or acid) is associated with weight increase and hyperinsulinemia, while topiramate causes weight loss. People with epilepsy are less likely to exercise which is protective against obesity. Mitochondrial dysfunction and adiponectin deficiency are common to epilepsy and T2DM. One possible mechanism for the comorbidity is mitochondrial dysfunction and adiponectin deficiency which promotes epilepsy, obesity, and T2DM. Another possible mechanism is that people with epilepsy are more likely to be obese due to lack of exercise and the effects of some antiseizure medications, which makes them susceptible to T2DM due to the development of mitochondrial dysfunction and adiponectin deficiency. A third mechanism is that people with epilepsy have greater mitochondrial dysfunction and lower adiponectin levels than people without epilepsy at baseline, which may exacerbate after treatment with antiseizure medications. Future research involving a combined genetic and molecular pathway approach will likely yield valuable insight regarding the comorbidity of epilepsy and T2DM.

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“…54 Oxidative stress parameters were elevated in VPA-treated patients with epilepsy as compared with the nontreated control. 55 The reactive oxygen species (ROS) production can cause direct damage to cellular DNA, protein, lipids, and can alter normal cell signaling pathways. 56 The VPA has been shown to increase ROS production and induce apoptosis in several cancer cell lines.…”

Section: Discussionmentioning

confidence: 99%

Valproic Acid Inhibits NA-K-2CL Cotransporter RNA Expression in Male But Not in Female Rat Thymocytes

et al. 2019

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Objective: The NKCC1 is a recognized tumorigenesis marker as it is important for tumor cell proliferation, differentiation, apoptosis, and tumor progression. The study aim was to investigate the effect of sodium valproate (VPA) on thymus NKCC1 RNA expression. Material and Methods: Wistar rats, age 4 to 5 weeks, were investigated in the control and VPA-treated male and female gonad-intact and castrated groups. The treatment duration with VPA 300 mg/kg/d was 4 weeks. Rat thymus was weighted; its lobe was taken for the expression of NKCC1 RNA determined by the real-time polymerase chain reaction method. Results: The RNA expression of the Slc12a2 gene was found to be significantly higher in the gonad-intact male control compared with the gonad-intact female control ( P = .04). There was a gender-related VPA treatment effect on NKCC1 RNA expression in thymus: The Slc12a2 gene RNA expression level was found to be decreased in VPA-treated gonad-intact males ( P = .015), and no significant VPA effects were found in the castrated males and in the gonad-intact and castrated females compared with the respective controls ( P > .05). Conclusions: The study showed a gender-related difference in the NKCC1 RNA expression in rat thymus. The VPA decreases the NKCC1 expression in the thymus only in gonad-intact male rats. The NKCC1 RNA expression downregulation by VPA could be important for further VPA pharmacological studies in oncology.

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Biochemical derangements related to metabolic syndrome in epileptic patients on treatment with valproic acid

Abstract: VPA treatment increased the risk factors for the development of metabolic syndrome such as hyperinsulinemia, insulin resistance and oxidative stress. However VPA treatment corrected the dyslipidemia of epileptic patients.

Cited by 24 publications

References 23 publications

Frequency of metabolic syndrome and insulin resistance in epileptic patients treated with sodium valproate or carbamazepine monotherapy: A Case-Control Study

Frequency of metabolic syndrome and insulin resistance in epileptic patients treated with sodium valproate or carbamazepine monotherapy: A Case-Control Study

Drivers for the comorbidity of type 2 diabetes mellitus and epilepsy: A scoping review

Valproic Acid Inhibits NA-K-2CL Cotransporter RNA Expression in Male But Not in Female Rat Thymocytes

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