Insulin and leptin levels in patients with schizophrenia or related psychoses - a comparison between different antipsychotic agents

Abstract

The higher insulin level in the patients receiving olanzapine than in those receiving conventional antipsychotics, despite similar BMI, points to a probable influence of olanzapine on insulin secretion. The correlation between the insulin levels and the clozapine concentration indicates, in addition, an influence of clozapine on insulin secretion. The gender difference in leptin, i.e. females normally having higher leptin levels than males, was found in the conventional agent group, but not in the olanzapine or clozapine groups, suggesting that also leptin regulation is altered during olanzapine or clozapine treatments. Moreover, it was mainly due to an increase of leptin in the males that leptin levels were equalized between sexes in the olanzapine group. We conclude that the influence of olanzapine and clozapine on both insulin and leptin levels might be associated with their weight-gain-inducing ability, while other mechanisms may be involved in the weight gain caused by conventional antipsychotics.

Zonisamide Prevents Olanzapine-Associated Hyperphagia, Weight Gain, and Elevated Blood Glucose in Rats

“…The typical clinical path toward diabetes is associated with increased adiposity and subsequent changes in insulin sensitivity; however, the rapid onset of diabetes associated with SGA administration, and the disappearance of hyperglycemia after discontinuation in patients suggests that the development of diabetes in patients on SGAs may be an acute drug-related effect (Rettenbacher et al, 2007). There is evidence that OLZ has direct effects on glucose regulation, possibly leading to hyperinsulinemia, hyperglycemia, and insulin resistance (Baptista et al, 2002;Graham et al, 2005;Melkersson and Hulting, 2001;Seemuller et al, 2005). Of note, recent experiments show that SGAs may impair both the insulinresponsive glucose transport system, as well as lipolysis in adipocytes (Vestri et al, 2007), demonstrating that antipsychotic drugs may differentially affect insulin action and metabolism through direct cellular effects in adipocytes.…”

Impact of atypical antipsychotic therapy on leptin, ghrelin, and adiponectin

“…Most, but not all, cross-sectional studies found that women have higher serum leptin levels than men, even when men had greater BMI (Melkersson and Hulting, 2001;Arranz et al, 2004;Haupt et al, 2005). When studied prospectively, this gender discrepancy was gradually effaced as men demonstrated greater increases in serum leptin during several trials (Baptista et al, 2000;Hagg et al, 2001;Zhang et al, 2003).…”

“…Cross-sectional studies with patients on various medications generally found that those exposed to olanzapine and clozapine were heavier, and had higher serum leptin levels (Hagg et al, 2001;Melkersson and Hulting, 2001;Melkersson and Dahl, 2003). Younger and thinner patients, regardless of medication, have lower serum leptin levels (Wang et al, 2006), and the association between the medication itself and leptin levels disappears when adjusted for differences in BMI (Smith et al, 2005).…”

“…Nonetheless, in many instances leptin levels increased significantly without significant changes in serum insulin, other glycemic or lipid measures (Zhang et al, 2004;Murashita et al, 2005;Sporn et al, 2005;Chiu et al, 2006;Hosojima et al, 2006;Atmaca et al, 2007). One cross-sectional study in bipolar subjects also found no correlation between any glucose or lipid parameter and leptin levels (Gergerlioglu et al, 2006), although a small number reported significant correlations between leptin and serum insulin (Baptista et al, 2000;Melkersson et al, 2000;Melkersson and Hulting, 2001), glucose (Wang et al, 2006) and serum triglycerides (Atmaca et al, 2003c); however, most of the authors reporting significant correlations did not control for BMI.…”

Alteraciones metabólicas asociadas al uso de terapia antipsicótica

“…Togo, encuentra un aumento en los niveles de esta proteína en pacientes en terapia prolongada con olanzapina y risperidona 39 , en tanto que el mismo grupo, en un estudio posterior, no encontró diferencias significativas en los niveles de adiponectina, pero sí elevación de leptina y disminución de ghrelina en pacientes expuestos a olanzapina por periodos menores a 4 semanas 40 . En relación a leptina, se ha planteado que se alteraría la relación fisiológica normal entre tejido adiposo y los niveles de circulantes 41,42 . La falta de consistencia en los resultados puede estar relacionada con la heterogeneidad clínica de esta enfermedad y las diferentes características de los pacientes seleccionados para estudio en cuanto a tiempo de evolución, uso de terapia antipsicótica y de otros fármacos asociados.…”