Do antiepileptics have any potential to induce insulin resistance? A comparison between levetiracetam and valproic acid

Year 2019, Volume: 5 Issue: 1, 88 - 93, 04.01.2019

Gökhan Özer

https://doi.org/10.18621/eurj.382538

Abstract

Objective: To explore whether levetiracetam and valproic acid are associated with insulin
resistance and to determine their effects on glucose and insulin levels among
different age groups.

Methods: Demographic data were
collected for epileptic patients from different age groups with a normal body
mass index and no chronic endocrine disease who were on levetiracetam or
valproic acid therapy. In addition to routine laboratory tests, fasting insulin
level was checked and Homeostatic Model Assessment for insulin
resistance calculated for all patients. Based on these
measurements, the effects of levetiracetam and valproic acid on laboratory
parameters were compared statistically.

Results: A total of 61 patients (30
males, 31 females) diagnosed with epilepsy were included in the study. Thirty-four
(55.7%) the patients were less than 15 years of age and the others were older.
Twenty-three (37.7%) patients were on valproic acid therapy and 38 (62.3%) patients
were receiving levetiracetam. Thirty-two (52.5%) the patients tested positive
for insulin resistance and others were insulin resistance-negative. Nine (28.1%)
patients on valproic acid treatment and 71.9% (n = 23) of patients on levetiracetam
treatment were insulin resistance-positive.

Conclusions: In the
present study, contrary to the published literature, levetiracetam was found to
be associated with further negative effects on insulin and blood glucose
metabolism compared to valproic acid. We determined that levetiracetam had a
distinct pharmacokinetic profile in pediatric patients as demonstrated by its
effects on glucose and insulin metabolism. 

Keywords

insulin resistance, levetiracetam, epilepsy, valproic asid

References

• [1] Edwards HE, Burnham WM, Ng MM, Asa S, MacLusky NJ. Limbic seizures alter reproductive function in the female rat. Epilepsia 1999;40:1370-7.
• [2] Edwards HE, Burnham WM, MacLusky NJ. Partial and generalized seizures affect reproductive physiology differentially in the male rat. Epilepsia 1999;40:1490-8.
• [3] Feeney DM, Gullotta FP, Gilmore W. Hyposexuality produced by temporal lobe epilepsy in the cat. Epilepsia 1998;39:140-9.
• [4] Herzog AG. A relationship between particular reproductive endocrine disorders and the laterality of epileptiform discharges in women with epilepsy. Neurology 1993;43:1907-10.
• [5] Banczerowski P, Csaba Z, Csernus V, Gerendai I. Lesion of the amygdala on the right and left side suppresses testosterone secretion but only left-sided intervention decreases serum luteinizing hormone level. J Endocrinol Invest 2003;26:429-34.
• [6] Gaitatzis A, Sander JW. The long-term safety of antiepileptic drugs. CNS Drugs 2013;27:435-55.
• [7] Jovanovic M, Jocic-Jakubi B, Stevanovic D. Adverse effects of antiepileptic drugs and quality of life in pediatric epilepsy. Neurol India 2015;63:353-9.
• [8] Perucca P, Gilliam FG. Adverse effects of antiepileptic drugs. Lancet Neurol 2012;11:792-802.
• [9] Shen C, Chen F, Zhang Y, Guo Y, Ding M. Association between use of antiepileptic drugs and fracture risk: a systematic review and meta-analysis. Bone 2014;64:246-53.
• [10] Svalheim S, Sveberg L, Mochol M, Tauboll E. Interactions between antiepileptic drugs and hormones. Seizure 2015;28:12-7.
• [11] Pennell PB. Hormonal aspects of epilepsy. Neurol Clin 2009;27:941-65.
• [12] Harden CL, Nikolov BG, Kandula P, Labar DR, Pannullo S. Effect of levetiracetam on testosterone levels in male patients. Epilepsia 2010;51:2348-51.
• [13] Taubøll E, Gregoraszczuk EL, Tworzydło A, Wójtowicz AK, Ropstad E. Comparison of reproductive effects of levetiracetam and valproate studied in prepubertal porcine ovarian follicular cells. Epilepsia 2006;47:1580-3.
• [14] Aygün F, Ekici B, Aydinli N, Aydin BK, Baş F, Tatli B. Thyroid hormones in children on antiepileptic therapy. Int J Neurosci 2012;122:69-73.
• [15] Martin CK, Han H, Anton SD, Greenway FL, Smith SR. Effect of valproic acid on body weight, food intake, physical activity and hormones: results of a randomized controlled trial. J Psychopharmacol 2009; 23:814-25.
• [16] Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412-9.
• [17] Wallace TM, Matthews DR. The assessment of insulin resistance in man. Diabet Med 2002;19:527-34.
• [18] Bonora E, Kiechl S, Willeit J, Oberhollenzer F, Egger G, Meigs JB, et al. Population-based incidence rates and risk factors for type 2 diabetes in white individuals: the Bruneck study. Diabetes 2004;53:1782-9.
• [19] Gungor N, Hannon T, Libman I, Bacha F, Arslanian S. Type 2 diabetes mellitus in youth: the complete picture to date. Pediatr Clin North Am 2005;52:1579-609.
• [20] Kurtoglu S, Hatipoglu N, Mazicioglu M, Kendirici M, Keskin M, Kondolot M. Insulin resistance in obese children and adolescents:HOMA-IR cut-off levels in the prepubertal and pubertal periods. J Clin Res Pediatr Endocrinol 2010;2:100-6.
• [21] Singh Y, Garg MK, Tandon N, Marwaha RK. A study of insulin resistance by HOMA-IR and its cut-off value to identify metabolic syndrome in urban Indian adolescents. J Clin Res Pediatr Endocrinol 2013;5:245-51.
• [22] Kaya A. Turan E, Uyar M, Bayram F, Turan Y. The prevalence of insulin resistance in the Turkish population: a study conducted with 3331 participants. EJMO 2017;1:202-6.
• [23] Beccarelli LM, Scherr RE, Newman JW, Borkowska AG, Gray IJ, Linnell JD, et al. Associations among fatty acids, desaturase and elongase, and insulin resistance in children. J Am Coll Nutr 2018;37:44-50.
• [24] Guzzaloni G, Grugni G, Mazzilli G, Moro D, Morabito F. Comparison between beta-cell function and insulin resistance indexes in prepubertal and pubertal obese children. Metabolism 2002;51:1011-6.
• [25] Tobisch B, Blatniczky L, Barkai L. Cardiometabolic risk factors and insulin resistance in obese children and adolescents: relation to puberty. Pediatr Obes 2015;10:37-44.