The effects of valproate and carbamazepine intake on serum leptin, insulin, lipid profiles, C-reactive protein levels and weight

Abstract

Objectives: This study aims to evaluate the effects of valproate (VPA) and carbamazepine (CBZ) intake on
serum leptin, insulin, lipid profiles, C-reactive protein (CRP) levels, C-peptid and weight.
Patients and methods: Twenty-nine using VPA (Group I), and 21 patients using CBZ (Group II) aged 1.5-15
years and 35 healthy children (Group III) were included.
Results: The rates of weight intake according to body mass index percentile increaase were 6.9 %, (2 cases) in
the Group I and 19 % (4 cases) in the Group II. In Group II, levels of only LDL-K and TK were significantly
higher than in Group I, but increasing of these lipids were not statistically significant compared with the control
group. However, no significant effect of serum levels of leptin, insulin, lipid profile, CRP, and C-peptide were
observed on weight intake.
Conclusion: The etiology of weight gain due to VPA and CBZ intake was not associated with hyperleptinemia,
hyperinsulinemia and hyperlipidemia. Multifactorial associations among heredity, socioeconomic factors,
dietary habits, enviromental factors and family education should be taken into consideration in the etiology of
weight gain secondary to antiepileptics. Further new studies about this subject should be performed.

Keywords

• Valproic acid
• carbamazepine
• obesity
• leptin
• insulin

The effects of valproate and carbamazepine intake on serum leptin, insulin, lipid profiles, C-reactive protein levels and weight

Abstract

Objectives: This study aims to evaluate the effects of valproate (VPA) and carbamazepine (CBZ) intake on serum leptin, insulin, lipid profiles, C-reactive protein (CRP) levels, C-peptid and weight. Patients and methods: Twenty-nine using VPA (Group I), and 21 patients using CBZ (Group II) aged 1.5-15 years and 35 healthy children (Group III) were included. Results: The rates of weight intake according to body mass index percentile increaase were 6.9 %, (2 cases) in the Group I and 19 % (4 cases) in the Group II. In Group II, levels of only LDL-K and TK were significantly higher than in Group I, but increasing of these lipids were not statistically significant compared with the control group. However, no significant effect of serum levels of leptin, insulin, lipid profile, CRP, and C-peptide were observed on weight intake. Conclusion: The etiology of weight gain due to VPA and CBZ intake was not associated with hyperleptinemia, hyperinsulinemia and hyperlipidemia. Multifactorial associations among heredity, socioeconomic factors, dietary habits, enviromental factors and family education should be taken into consideration in the etiology of weight gain secondary to antiepileptics. Further new studies about this subject should be performed

Keywords

• Valproic acid
• carbamazepine
• obesity
• leptin
• insulin

References

1. Eşkazan E, Denizbaşı A: Antiepileptik ilaçlar. Özüner Z, Süzer Ö (editörler): Temel ve Klinik Farmakoloji. İstanbul. Barış Kitabevi. 23:483-510, 1995.
2. Krauss G, Crone N: Non-CNS side effects of antiepileptic drugs. Clinical update. http//www.medscape.com., 2001
3. Pylvanen V, Knip M, Pakarinen A, Kotila M, Turkka J, Isojarvi JI: Serum insulin and leptin levels in valproate-associated obesity. Epilepsia. 43(5):514-17, 2002.
4. Jallon P, Picard F: Bodyweight gain and anticonvulsants: a comparative review. Drug Saf. 24(13):969-78, 2001.
5. Isojarvi JI, Laatikainen TJ, Knip M, Pakarinen AJ, Juntunen KT, Myllyla VV: Obesity and endocrine disorders in women taking valproate for epilepsy. Ann Neurol. 39(5):579-84, 1996.
6. Chengappa KN, Chalasani L, Brar JS, Papepally H, Houck P, Levine J: Changes in body weight and body mass index among psychiatric patients receiving lithium, valproate, or topiramate: an open- label, nonrandomized chart review. Clin Ther. 24(10):1576-84, 2002.
7. Wirrell EC: Valproic acid-associated weight gain in older children and teens with epilepsy. Pediatr Neurol. 28(2):126-9, 2003.
8. Verrotti A, Basciani F, Morresi S, Martino M, Morgese G, Chiarelli F: Serum leptin changes in epileptic patients who gain weight after therapy with valproic acid. Neurology. 53(1):230-2, 1999.

9. Isojarvi JI, Pakarinen AJ, Myllyla VV: Serum lipid levels during carbamazepine medication. A prospective study. Arch Neurol. 50(6):590-3, 1993.
10. Güven F, Zorlu Y, Yensel N: Valproik asit ve Karbamazepin kullanan epilepsili kadın hastalarda polikistik over sendromu, insülin düzeyi ve obezite. Epilepsi. 9(1):21-6, 2003.
11. Alikaşifoğlu A, Yordam N: Obezitenin tanımı ve prevalansı. Katkı Pediatri Dergisi. 21(4): 475-81, 2000.
12. Friedewald WT, Lewry RI, Fredrickson DS: Estimation of low density lipoprotein cholesterol in plasma without use of preperative ultracentrifuge. Clin Chem. 18:499-502, 1972.
13. Turanlı G: Epilepsi ve izlemi. Katkı Pediatri Dergisi. 20: 385-95, 1999.
14. Corman CL, Leung NM, Guberman AH: Weight gain in epileptic patients during treatment with valproic acid: a retrospective study. Can J Neurol Sci. 24(3): 240-4, 1997.
15. Berberoğlu M: Obezite ve glukoz intoleransı. Cinaz P, Bideci A (editörler): Çocuk ve ergen obezitesi. Ankara: Pediatrik Endokrinoloji ve Oksoloji Derneği. 31-6, 2002.
16. Blum WF, Englaro P, Hanitsch S, Juul A, Hertel NT, Müller J et al: Plasma leptin levels in healthy children and adolescents: dependence on body mass index, body fat mass, gender, pubertal stage, and testosterone. J Clin Endocrinol Metab. 82(9):2904-10, 1997.
17. Palou A, Serra F, Bonet ML, Pico C: Obesity: molecular basis of a multifactorial problem. Eur J Nutr. 39(4):127-44, 2000.
18. Havel PJ, Karakas SK, Mueller W, Johnson PR, Gingerich RL, Stern JS: Relationship of plasma leptin to plasma insülin and adiposity in normal weight and overweight women: effects of dietary fat content and sustained weight loss. J Clin Endocrinol Metab. 81(12):4406-13, 1996.
19. McLaughlin T, Abbasi F, Lamendola C, Liang L, Reaven G, Schaff P et al: Differentiation between obesity and insulin resistance in the association with C-reactive protein. Circulation. 106(23):2908-12, 2002.
20. Yudkin JS, Stehouwer CDA, Emesis JJ, Coppack SW: C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: A potential role for cytokines originating from adipose tissue?. Arterioscler Thromb Vasc Biol. 19(4):972- 8, 1999.
21. Liu S, Manson JE, Burig JE, Stampfer MJ, Willett WC, Ridker PM: Relation between a diet with a high glycemic load and plasma concentrations of high-sensitivity C-reactive protein in middle-aged women. Am J Clin Nutr. 75(3):492-8, 2002.
22. Ford ES: Body mass index, diabetes, and C-reactive protein among U.S. adults. Diabetes Care. 22(12):1971-7, 1999.
23. Escobar-Morreale HF, Villundeas G, Botella-Carretero JI, Sancho J, San Millan JL: Obesity, and not insulin resistance, is the major determinant of serum inflammatory cardiovascular risk markers in pre-menopausal women. Diabetologia. 46(5):625-33, 2000.
24. Visser M, Bouter LM, McQuillan GM, Wener MH, Harris BT: Elevated C- reactive protein levels in overweight and obese adults. JAMA. 282(22): 2131-35, 1999.
25. Heldenberg D, Harel S, Holtzman M, Levtow O, Tamir I: The effect of chronic anticonvulsant therapy on serum lipids and lipoproteins in epileptic children. Neurology. 33(4):510-3, 1983.
26. Bramswig S, Kersiek A, Sudhop T, Luers C, Bergman KV, Berthold HK: Carbamazepine increases atherogenic lipoproteins: mechanism of action in male adults. Am J Physiol Heart Circ Physiol. 282(2):H704-H716, 2002.