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Increase
in postprandial serum insulin levels in epileptic patients with valproic acid
therapy
Luef G,
Abraham I, Hoppichler F, Trinka E, Unterberger I, Bauer G, Lechleitner M
Department
of Neurology, University Hospital Innsbruck, Innsbruck, Austria
A
significant weight gain and increase in serum leptin levels in the course of
antiepileptic treatment with valproic acid (VPA) 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.
We have studied clinical and laboratory effects of VPA treatment in a cohort of
female patients (n = 22) and in patients treated with carbamazepine (CBZ) or
lamotrigine monotherapy (n = 21).
All study participants underwent an oral glucose tolerance test (OGTT) with 75 g
glucose.
Body mass index (BMI) in the VPA group was higher (28.1 +/- 3.6 kg/m(2)) than in
the control group (23.9 +/- 3.7 kg/m(2)) (P <.039).
While plasma glucose, serum leptin, insulin, and C-peptide levels did not differ
significantly between the study groups in the fasting state, postprandial (pp)
insulin and proinsulin levels were found to be significantly higher in the VPA
than in the control group.
In the course of the OGTT, serum insulin levels reached their peak values 1 hour
postprandially with 68.8 +/- 10.0 microU/mL in the VPA group and 49.8 +/- 11.2
microU/mL in the control group (P <.042).
After 2 hours, the corresponding serum insulin levels were 48.5 +/- 25.2 microU/mL
and 34.1 +/- 17.2 microU/mL (P <.048) and the proinsulin levels 52.5 +/- 30.2
pmol/L and 29.5 +/- 12.0 pmol/L (P <.017).
While BMI values in the non-VPA group showed a significant correlation only with
the fasting values of insulin, proinsulin, and C-peptide, the BMI values of the
VPA-treated group were also positively related to the 2-hour pp levels of
insulin (R =.690; P <.001), proinsulin (R =.667; P <.001) and C-peptide (R
=.502; P <.017).
VPA is a fatty acid derivative, competes with free fatty acids (FFA) for albumin
binding, and acts as a gamma aminobutyric acid (GABA)-ergic agonist, mechanisms,
which are known to be involved in pancreatic beta-cell regulation and insulin
secretion.
Therefore, it might be suspected that VPA therapy is associated with increased
glucose stimulated pancreatic secretion and thus a higher body weight in the VPA
group.
Copyright 2002, Elsevier Science (USA). All rights reserved.
PMID:
12370846 [PubMed - indexed for MEDLINE]
Source:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12370846&dopt=Abstract
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