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How can antipsychotics cause diabetes mellitus? Insights based on receptor-binding profiles, humoral factors and transporter proteins

Published online by Cambridge University Press:  16 April 2020

F.C.J. Starrenburg  and
J.P.A.M. Bogers
F.C.J. Starrenburg*
Affiliation:
Rivierduinen Psychiatric Centre, Midden Holland District, JP Thijsselaan 45, 2803RTGouda, Netherlands
J.P.A.M. Bogers*
Affiliation:
Rivierduinen Psychiatric Centre, Haagstreek District, PO Box 422, 2260AKLeidschendam, Netherlands
*
1Tel.: +31 182563700; fax: +31 182563726.
*Corresponding author. Tel.: +31 704441122; fax: +31 704441074. E-mail addresses: f.starrenburg@ggzmiddenholland.nl (F. C. J. Starrenburg), j.bogers@ggzhaagstreek.nl (J.P.A.M Bogers).
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Abstract

The prevalence of Diabetes Mellitus (DM) is becoming a serious public health problem. The use of atypical antipsychotics has been associated with disruption of the glucose metabolism and therefore with causing DM. The underlying mechanisms are unknown, but knowledge of the differences between the pharmacological features of various antipsychotics combined with their diabetogenic profile might help us to understand those mechanisms. This article describes how the binding of various essential receptors or transporters in essential body tissues, adipose tissue, pancreatic tissue and liver and skeletal muscle tissue can cause disruption of the glucose metabolism. With such knowledge in mind one can try to explain the differences between the diabetogenic propensities of various antipsychotics. It is well known that clozapine and olanzapine cause weight gain and DM, whereas aripiprazole and ziprasidone have much less disruptive clinical profiles. The most significant risk factor for adiposity seems to be strong blocking of histaminergic receptors. An agonistic activity on serotonergic-1a receptors, with a very low affinity for muscarinergic-3 receptors, might protect against the development of DM. More data will become available which may help to solve the puzzle.

Keywords

Diabetes mellitusAntipsychoticsReceptor-bindingAdipocytokinesWeightGlucose
Type
Review
Information
European Psychiatry , Volume 24 , Issue 3 , April 2009 , pp. 164 - 170
Copyright
Copyright © Elsevier Masson SAS 2009

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