Zeitschrift für Epileptologie

, Volume 19, Issue 3, pp 195–198 | Cite as

Pankreashormone und Leptin

BEITRAG ZUM THEMENSCHWERPUNKT
  • 47 Downloads

Zusammenfassung

Insulin, ein Hormon des endokrinen Pankreas, kann durch eine antiepileptische Therapie mit Valproat vermehrt aus den β-Zellen sezerniert werden. Experimentelle Studien geben Hinweise für eine direkte Wirkung von Valproat auf die β-Zellen des Pankreas. Die Folge sind eine Hyperinsulinämie und später eine Insulinresistenz, die wiederum streng mit einer Gewichtszunahme und einem möglichen metabolischen Syndrom einhergeht. Bei weiblichen Patienten kann die Umverteilung des Körperfettgewebes, vom gynoiden zum androiden Typus (Stammfettsucht), auch die Entstehung eines polyzystischen Ovar-Syndroms begünstigen. Durch den Einfluss auf den Fettstoffwechsel in der Leber kann die Entstehung einer nicht alkoholischen Fettleber eine zusätzliche Langzeitnebenwirkung von Valproat sein. Leptin, ein Proteohormon, wird aus den Fettzellen sezerniert und steht ebenso im engen Zusammenhang mit einer antiepileptischen Therapie mit Valproat und einer Körpergewichtszunahme. Da es eine zentrale Appetithemmung erzeugt, wurden diesbezüglich auch Untersuchungen mit Topiramat durchgeführt.

Schlüsselwörter

Insulin Gewichtszunahme Epilepsie Antiepileptika Valproat 

Pancreas hormones and leptin

Abstract

A significant weight gain and increase in serum leptin levels in the course of antiepileptic treatment with valproic acid has been described in several clinical studies. With respect to the long treatment period in antiepileptic therapy, these side effects might increase insulin resistance and metabolic risk factors. The effect of valproate on insulin secretion in pancreatic islet cells was studied in in vitro experiments with islets from pancreases of multiorgan donors. It can be speculated that an increase in pancreatic insulin secretion under chronic valproate treatment enhances appetite and energy storage and is related to the observed weight gain. Changes in weight seem to affect the expression of PCOS in women with PCO, with a gain in weight being associated with a worsening of the symptoms of PCOS. Nonalcoholic fatty liver disease was defined recently as another symptom of insulin resistance in valproate treated patients. Leptin secreted from peripheral adipose tissue acts centrally within the mammalian hypothalamus to reduce appetite and promote a negative energy balance, as observed in Topiramate-treated patients. Elevated circulating leptin concentrations in obese humans fail to act in this way.

Key words

Insulin weight gain epilepsy antiepileptic drugs valproate 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Bergmann RN, Ider YZ, Bowden CR (1979) Quantitative estimation of insulin sensitivity. Am J Physiol 236:667–677Google Scholar
  2. 2.
    Biton V, Mirza W, Montouris G et al (2001) Weight gain associated with valproate and lamotrigine monotherapy in patients with epilepsy. Neurology 56:172–177PubMedCrossRefGoogle Scholar
  3. 3.
    Breum L, Astrup A, Gram L et al (1992) Metabolic changes through treatment with valproate in humans: Implications for untoward weight gain. Metabolism 41:666–670PubMedCrossRefGoogle Scholar
  4. 4.
    Büchler MW, Uhl W, Malfertheiner P (2004) Pankreaserkrankungen. Akute Pankreatitis, Chronische Pankreatitis, Tumore des Pankreas. Karger, BaselGoogle Scholar
  5. 5.
    Campfield LS, Smith FJ, Burn P (1996) The OB protein (leptin) pathway: a link between adipose tissue mass and central neural networks. Horm Metab Res 28:619–632PubMedGoogle Scholar
  6. 6.
    Cassader M, Gambino R, Depetris N et al (2001) Postprandial triglyceriderich lipoprotein metabolism and insulin sensitivity in nonalcoholic steatohepatitis patients. Lipids 36:117–1124Google Scholar
  7. 7.
    Dandona P, Aljada A, Bandyopadhyay A (2004) Inflammation: the link between insulin resistance, obesity and diabetes. Trend Immunol 25(1):4–7CrossRefGoogle Scholar
  8. 8.
    Dinesen H, Gram L, Andersen T et al (1984) Weight gain during treatment with valproate. Acta Neurol Scand 69:65–69CrossRefGoogle Scholar
  9. 9.
    Friedman JM, Halaas JL (1998) Leptin and the regulation of body weight in mammals. Nature 395:763–770PubMedCrossRefGoogle Scholar
  10. 10.
    Isojärvi JIT, LaatikainenTJ, Pakarinen AJ, Juntunen KTS, Myllyla VV (1993) Polycystic ovaries and hyperandrogenism in women taking valproate for epilepsy. N Engl J Med 329:1383–1388PubMedCrossRefGoogle Scholar
  11. 11.
    Isojärvi JI, Laatikainen TJ, Knip M et al (1996) Obesity and endocrine disorders in women taking valproate for epilepsy. Ann Neurol 39:579–584PubMedCrossRefGoogle Scholar
  12. 12.
    Isojärvi JI, Rattya J, Myllyla VV et al (1998) Valproate, lamotrigine, and insulin mediated risks in women with epilepsy. Ann Neurol 43:446–451PubMedCrossRefGoogle Scholar
  13. 13.
    Luef G, Abraham I, Haslinger M et al (2002) Polycystic ovaries, obesity and insulin resistance in women with epilepsy: a comparative study of carbamazepine and valproic acid in 105 women: J Neurol 249:835–841PubMedCrossRefGoogle Scholar
  14. 14.
    Luef G, Abraham I, Trinka E et al (2002) Hyperandrogenism, postprandial hyperinsulism and the risk of PCOS in a cross sectional study of women with epilepsy treated with valproate. Epilepsy Res 48:91–102PubMedCrossRefGoogle Scholar
  15. 15.
    Luef G, Abraham I, Hoppichler F et al (2002) Increase in postprandial serum insulin levels in epileptic patients with valproic acid therapy. Metabolism 10:1274–1278CrossRefGoogle Scholar
  16. 16.
    Luef G, Lechleitner M, Bauer G, Hengster P (2003) Valproic acid modulates islet cell insulin secretion: a possible mechanism of weight gain in epilepsy patients. Epilepsy Res 55:53–58PubMedCrossRefGoogle Scholar
  17. 17.
    Luef GJ, Waldmann M, Sturm W et al (2004) Valproat therapy and nonalcoholic fatty liver disease. Ann Neurol 55:729–732PubMedCrossRefGoogle Scholar
  18. 18.
    Messenheimer J (2003) Higher androgens and weight gain with valproate compared with lamotrigine for epilepsy. Epilepsy Res 54:189–199PubMedCrossRefGoogle Scholar
  19. 19.
    Morrell M, Isojärvi J, Taylor AE et al (2002) Serum insulin and leptin levels in valproate-associated obesity. Epilepsia 43:514–517CrossRefGoogle Scholar
  20. 20.
    Rett K (1999) The relation between insulin resistance and cardiovascular complications of the insulin resistance syndrome. Diab Obes Metab 1(Suppl 1):8–16CrossRefGoogle Scholar
  21. 21.
    Verrotti A, Basciani F, De Simone M et al (2002) Insulin resistance in epileptic girls who gain weight after therapy with valproic acid. J Child Neurol 17:265–268PubMedGoogle Scholar

Copyright information

© Steinkopff-Verlag 2006

Authors and Affiliations

  1. 1.Medizinische Universität InnsbruckUniversitätsklinik für NeurologieInnsbruckAustria

Personalised recommendations