Abnormal glucose metabolism in patients treated with antipsychotics

Abstract

Second-generation (atypical) antipsychotic medications are of great benefit to a wide variety of people with psychiatric disorders, especially patients with schizophrenia. However, one constellation of adverse effects is an increased risk of obesity, diabetes, and metabolic syndrome. Increasing numbers of reports concerning impaired glucose tolerance, diabetes, and ketoacidosis have raised concerns about a possible association between abnormal glucose metabolism and treatment with atypical antipsychotics, although the question is still debated because of the presence of many confounding factors. A close relationship between drug-induced weight gain and risk of diabetes has been reported, emphasizing the role of insulin resistance. However, some cases of diabetes developed independently of weight gain, rather rapidly and possibly progressing to ketoacidosis, thus arguing for a severe impairment of insulin secretion. Another debated question is whether diabetes risk is a class action or a differential action. Although not fully scientifically proven yet, available evidence suggests that clozapine and olanzapine have a higher propensity to induce diabetes and metabolic syndrome compared with other atypical antipsychotic drugs, risperidone and quetiapine. Despite more limited available data, amisulpride, aripiprazole and ziprazidone showed less likelihood of precipitating diabetes. Interestingly, reversibility of drugrelated diabetes has been reported with aripiprazole. The choice of atypical antipsychotic medication for a specific patient depends on many factors, but the likelihood of developing diabetes should become an important consideration. When prescribing an atypical antipsychotic, a commitment to careful baseline screening and follow-up monitoring is essential in order to mitigate the risk of developing diabetes and associated complications.Keywords: antipsychoticsa; schizophrenia ; diabetes ; impaired glucose tolerance ; metabolic syndrome ; review RésuméLes antipsychotiques de seconde génération, appelés aussi antipsychotiques atypiques, ont apporté une aide précieuse dans la prise en charge de nombreux patients psychiatriques, en particulier ceux avec schizophrénie. Cependant, ils semblent associés à une constellation d'effets indésirables métaboliques, avec un risque accru d'obésité, de diabète et de syndrome métabolique. Un nombre croissant de publications à propos de cas de diminution de tolérance au glucose, de diabète et d'acidocétose chez des patients traités avec des antipsychotiques atypiques plaident pour une association causale possible entre une anomalie du métabolisme du glucose et le traitement par antipsychotique atypique, même si la question reste controversée suite à la présence de nombreux facteurs confondants. Une relation étroite entre la prise de poids induite par la médication et le risque accru de diabète a été rapportée, insistant sur le rôle de l'insulinorésistance. Pourtant, certains cas de diabète se développent indépendamment de toute prise pondérale, avec une évolution...

Central nervous system: a conductor orchestrating metabolic regulations harmed by both hyperglycaemia and hypoglycaemia

“…Several underlying mechanisms have been proposed to explain this intimate connection between psychiatric disorders and metabolic disturbances, including DM [9].…”

Undiagnosed metabolic syndrome and other adverse effects among clozapine users of Xhosa descent

“…Therefore, a direct diabetogenic effect of clozapine could not be proven by these data, despite previous reports in other population groups suggesting such a direct effect. [8,20] It is possible that the high incidence of undiagnosed diabetes in our group may be attributable to other factors (e.g. family history, physical inactivity, abdominal obesity, poor diet).…”

“…[1] It has long been known that clozapine is associated with weight gain [3] and more recently it has also been shown that there is an increased risk among clozapine users for developing metabolic syndrome. [4][5][6][7] It has been suggested that clozapine may have a direct effect on glucose regulation, independent of weight gain, [8] and Koller et al [2] suggested a causal relationship between clozapine treatment and diabetes.…”

The Impact of Cardiometabolic Risk in Patients with Severe Mental Illness: From Evidence to Clinical Management

“…The combined blockade of H1 and 5HT2C receptors has been especially associated with weight gain -sometimes profoundand could explain why atypical antipsychotics such as olanzapine and clozapine, which have high 5HT2C as well as H1 affinities, might have greater weight gain liabilities than an agent such as chlorpromazine, which lacks appreciable 5HT2C effects, even though it has H1 antagonist properties (Cutler et al, 2008;Kroeze et al, 2003). The high interindividual variability in medication-induced weight gain suggests that genetic factors influence the risk to gain weight (Holt and Peveler, 2009 (Scheen and De Hert, 2007;Okumura et al, 2010;Citrome et al, 2007), the risk being 1.3 fold higher in people with schizophrenia taking SGAs compared with those receiving FGAs (M. Smith et al, 2008). However, the risk of diabetes-related adverse events differs between SGAs.…”