Elevated Levels of Insulin, Leptin, and Blood Lipids in Olanzapine-Treated Patients With Schizophrenia or Related Psychoses
J Clin Psychiatry 2000;61:742-749
© Copyright 2014 Physicians Postgraduate Press, Inc.
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Background: The aim of this study was to
investigate the influence of the antipsychotic agent olanzapine
on glucose-insulin homeostasis to explain possible mechanisms
behind olanzapine-associated weight gain.
Method: Fourteen patients on treatment with
olanzapine (all meeting DSM-IV criteria for schizophrenia or
related psychoses) were studied. Fasting blood samples for
glucose, insulin, the growth hormone (GH)-dependent insulin-like
growth factor I, and the insulin-dependent insulin-like growth
factor binding protein-1 (IGFBP-1) were analyzed, as well as GH,
leptin, and blood lipid levels and the serum concentrations of
olanzapine and its metabolite N-desmethylolanzapine. In
addition, body mass index (BMI) was calculated. Moreover, weight
change during olanzapine treatment was determined.
Results: Twelve of the 14 patients reported
weight gain between 1 and 10 kg during a median olanzapine
treatment time of 5 months, whereas data were not available for
the other 2 patients. Eight patients (57%) had BMI above the
normal limit. Eleven patients were normoglycemic, and 3 showed
increased blood glucose values. Most patients (10/14; 71%) had
elevated insulin levels (i.e., above the normal limit).
Accordingly, the median value of IGFBP-1 was significantly lower
for the patients in comparison with healthy subjects. Moreover, 8
(57%) of 14 patients had hyperleptinemia, 62% (8/13) had
hypertriglyceridemia, and 85% (11/13) hypercholesterolemia.
Weight change correlated positively to blood glucose levels and
inversely to the serum concentration level of N-desmethylolanzapine.
Additionally, the levels of blood glucose, triglycerides, and
cholesterol correlated inversely to the serum concentration of N-desmethylolanzapine.
Conclusion: Olanzapine treatment was associated
with weight gain and elevated levels of insulin, leptin, and
blood lipids as well as insulin resistance, with 3 patients
diagnosed to have diabetes mellitus. Both increased insulin
secretion and hyprleptinemia may be mechanisms behind
olanzapine-induced weight gain. Moreover, it is suggested that
the metabolite N-desmethylolanzapine, but not olanzapine,
has a normalizing effect on the metabolic abnormalities.