Changes in Glucose and Cholesterol Levels in Patients With Schizophrenia Treated With Typical or Atypical Antipsychotics

Lindenmayer, Jean Pierre; Czobor, Pál; Volavka, Jan; Citrome, Leslie; Sheitman, Brian; McEvoy, Joseph P.; Cooper, Thomas B.; Chakos, Miranda; Lieberman, Jeffrey A.

doi:10.1176/appi.ajp.160.2.290

Cited by 421 publications

(258 citation statements)

References 54 publications

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“…Interestingly, a number of studies show evidence for acute, non-adiposity linked mechanisms (Houseknecht et al, 2005) and lack of correlation between weight gain and changes in glucose metabolism (Meyer, 2002;Lindenmayer et al, 2003;Simpson et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

Sacher

Mossaheb

Spindelegger

et al. 2007

Neuropsychopharmacol

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Atypical antipsychotics have been linked to a higher risk for glucose intolerance, and consequentially the development of type 2 diabetes mellitus (DM2). We have therefore set out to investigate the acute effects of oral administration of olanzapine and ziprasidone on whole body insulin sensitivity in healthy subjects. Using the standardized hyperinsulinemic euglycemic clamp technique we compared whole body insulin sensitivity of 29 healthy male volunteers after oral intake of either olanzapine 10 mg/day (n ¼ 14) or ziprasidone 80 mg/day (n ¼ 15) for 10 days. A significant decrease (po0.001) in whole body insulin sensitivity from 5.7 ml/h/kg ( ¼ mean, SM ¼ 0.4 ml/h/kg) at baseline to 4.7 ml/h/kg ( ¼ mean, SM ¼ 0.3 ml/h/kg) after oral intake of olanzapine (10 mg/day) for 10 days was observed. The ziprasidone (80 mg/day) group did not show any significant difference (5.2 ± 0.3 ml/h/kg baseline vs 5.1 ± 0.3 ml/h/kg) after 10 days of oral intake. Our main finding demonstrates that oral administration of olanzapine but not ziprasidone leads to a decrease in whole body insulin sensitivity in response to a hyperinsulinemic euglycemic challenge. Our finding is suggestive that not all atypical antipsychotics cause acute direct effects on glucose disposal and that accurate determination of side effect profile should be performed when choosing an atypical antipsychotic.

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Section: Discussionmentioning

confidence: 99%

Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

Sacher

Mossaheb

Spindelegger

et al. 2007

Neuropsychopharmacol

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“…With such a rapid onset, weight gain is unlikely to be the main stimulus for the development of the diabetes. A prospective randomised trial comparing the classical antipsychotic haloperidol with the three atypicals clozapine, olanzapine and risperidone found no relationship between glucose change and weight gain at endpoint, thereby confirming the independence of these two measures [3]. The second argument is the dramatic clinical presentation of diabetes in schizophrenia.…”

Section: To the Editormentioning

confidence: 97%

Immunological characteristics of diabetes in schizophrenia

2005

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Abbreviations IA2: insulinoma antigen 2 . LADA: latent autoimmune diabetes of adults To the EditorIn 1899, Henry Maudsley, the first psychiatrist to link diabetes to psychiatric illness, wrote that "diabetes is a disease which often shows itself in families in which insanity prevails" [1]. With this observation, Maudsley suggested that patients with schizophrenia are genetically predisposed to diabetes. The introduction of chlorpromazine (in 1953) and, more recently, the atypical antipsychotics was followed by an increase in the number of cases of new-onset diabetes and the worsening of glycaemic control in cases of existing diabetes in patients with schizophrenia [2]. These findings suggest an iatrogenic, rather than a genetic, origin of diabetes in schizophrenia, in the form of antipsychoticinduced weight gain. However, this debate has not, as yet, been settled.In general, diabetes associated with schizophrenia is classified as type 2 diabetes. However, there are two arguments against this classification. The first argument is the rapid onset of schizophrenia-associated diabetes: over 80% of patients who develop diabetes do so within 6 months of initiating antipsychotic therapy [2]. With such a rapid onset, weight gain is unlikely to be the main stimulus for the development of the diabetes. A prospective randomised trial comparing the classical antipsychotic haloperidol with the three atypicals clozapine, olanzapine and risperidone found no relationship between glucose change and weight gain at endpoint, thereby confirming the independence of these two measures [3]. The second argument is the dramatic clinical presentation of diabetes in schizophrenia. There is an enhanced risk of metabolic complications, such as ketosis, acidosis and ketoacidosis, which are associated with a mortality rate of 26.5% [4][5][6]. These features are suggestive of type 1 diabetes or latent autoimmune diabetes of adults (LADA) rather than type 2 diabetes.Type 1 diabetes and LADA are characterised by diabetes-related antibodies, i.e. antibodies against insulin, GAD and insulinoma antigen 2 (IA2), which are found in over 80% of type 1 diabetic subjects and in fewer than 5% of the general population [7,8]. The aim of this study was to determine the prevalence of the three diabetes-related antibodies in schizophrenic patients, thereby establishing whether autoimmune phenomena play a role in diabetes associated with schizophrenia.Patients (81 men [68.1%], 38 women [31.9%]; mean age 41.5 years [SD=10.9, range 19-65]) gave informed consent to participate in the study, which was approved by the Ethics Committee of the University of Utrecht. The psychiatric diagnosis was based on the shortened version of the

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“…People with schizophrenia have a more than twofold higher risk of death from CVD relative to the general population (Osby et al, 2000). The increased cardiovascular risk may be related to the higher prevalence of Type 2 diabetes combined with multiple additional risk factors that are common in this population, including obesity (Daumit et al, 2003), physical inactivity (Daumit et al, 2005), poor diet (McCreadie, 2003), and high rates of smoking (de Leon et al, 1995), as well as treatment with psychotropic medications that promote weight gain and hyperglycemia (Allison et al, 1999;Lindenmayer et al, 2003).Robust evidence suggests that control of blood pressure and cholesterol levels leads to fewer cardiovascular events and reduced mortality in patients with Type 2 diabetes (American Diabetes Association, 2004). The American Diabetes Association (ADA; 2004) has established standards of medical care that recommend target goals for both blood pressure and cholesterol levels in these patients.…”

mentioning

confidence: 99%

Extent and Management of Cardiovascular Risk Factors in Patients With Type 2 Diabetes and Serious Mental Illness

Kreyenbuhl¹,

Dickerson²,

Medoff³

et al. 2006

Journal of Nervous &Amp; Mental Disease

103

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Cardiovascular disease is the leading cause of death in Type 2 diabetes, which commonly occurs in patients with serious mental illnesses (SMIs). We determined the extent to which patients with diabetes and SMI, relative to diabetes patients without SMI, met American Diabetes Association goals for cholesterol and blood pressure, met criteria for the metabolic syndrome, and were prescribed medications known to reduce cardiovascular events. We found that less than half of diabetes patients, both with and without SMI, met recommended goals for cholesterol levels; even fewer had adequate blood pressure control. In addition, a substantial proportion of all diabetes patients met metabolic syndrome criteria. However, diabetes patients with SMI were less likely to be prescribed cholesterol-lowering statin medications, angiotensin-converting enzyme inhibitors, and angiotensin receptor blocking agents than diabetes patients without SMI. Patients with both diabetes and SMI are treated less aggressively for high cardiovascular risk than diabetes patients without mental disorders. KeywordsType 2 diabetes; serious mental illness; cardiovascular risk; metabolic syndrome In 2002, Type 2 diabetes affected approximately 6.3% of the US population at an estimated cost of $132 billion (American Diabetes Association, 2003;Engelgau et al., 2004). Type 2 diabetes is associated with a twofold to fourfold increased risk for major cardiovascular events and is considered a coronary heart disease risk equivalent that confers a level of risk equal to that in patients with pre-existing cardiovascular disease (CVD; Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, 2001). Cardiovascular and cerebrovascular complications of Type 2 diabetes account for 60% to 75% of deaths from this disease (Stamler et al., 1993). Metabolic abnormalities characteristic of Type 2 diabetes including insulin resistance and dyslipidemias contribute in part to the increased CVD risk, with emerging evidence suggesting that persistent hyperglycemia may also play a role (Nathan et al., 2003;Selvin et al., 2004 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript frequent co-occurrence of hypertension, overweight and obesity, smoking, and reduced physical activity in patients with diabetes confers an additive CVD risk that exceeds the sum of their risks individually (Wilson et al., 1998). There is also mounting evidence that the cluster of risk factors that comprise the metabolic syndrome increases the risk for cardiovascular mortality , and by definition, would be expected to occur disproportionately in people with Type 2 diabetes.Persons with serious mental illnesses such as schizophrenia have an increased risk for Type 2 diabetes (Dixon et al., 2000) and other co-occurring medical conditions. Life expectancy in people with schizophrenia is 20% shorter than that of the general population (Newman and Bland, 1991), with the excess mortality largely attributed to higher rates of CVD (Brown et al., 2000;Os...

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Changes in Glucose and Cholesterol Levels in Patients With Schizophrenia Treated With Typical or Atypical Antipsychotics

Cited by 421 publications

References 54 publications

Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

Effects of Olanzapine and Ziprasidone on Glucose Tolerance in Healthy Volunteers

Immunological characteristics of diabetes in schizophrenia

Extent and Management of Cardiovascular Risk Factors in Patients With Type 2 Diabetes and Serious Mental Illness

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