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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Olanzapine is a novel antipsychotic, approved for the acute and maintenance treatment of schizophrenia and bipolar I disorder. Despite the publicity regarding reported adverse events with the novel antipsychotics, such as weight gain and Type II diabetes mellitus, olanzapine remains a useful and important medicine. It is a selective monoaminergic antagonist with high-affinity binding to a number of receptors thought to be implicated in some psychotic and mood symptoms. The complex pharmacology of olanzapine has lead to studies exploring its use in treating substance abuse, aggression/violence, borderline personality disorder, schizotypal personality disorder, obsessive-compulsive disorder and as a neuroprotective agent in schizophrenia. As the pharmacology of olanzapine and other novel antipsychotics becomes better understood, future effective treatment strategies are likely to match an individual's genetic makeup and receptor profiles to the most compatible agent.
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PMID:Olanzapine: a 5-year perspective. 1678 5

Depression affects millions of people in the United States. Drugs used to treat depression can lead to weight gain, which could predispose a person to type 2 diabetes. Also, certain medications that may be used to treat depression with psychotic features can lead to metabolic syndrome and new-onset diabetes. Diabetes is another chronic health care condition that affects millions of people in the United States. Diabetes is the leading cause of nontraumatic amputations and a leading cause of blindness. Both conditions can result in a lower quality of life. Clinicians face challenges in treating either condition, but can face greater ones when the conditions occur together. This article reviews the literature concerning depression and diabetes.
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PMID:Diabetes and depression: a review of the literature. 1727 May 91

Schizophrenia and other psychotic disorders are associated with increased risk of developing type 2 diabetes. However, previous studies are mainly based on clinical samples where the comorbidity may be stronger. We investigated in a general population survey the prevalence of type 2 diabetes in persons with psychotic disorders and in users of antipsychotic medication. The study was based on a nationally representative two-stage cluster sample of 8,028 persons aged 30 or over from Finland. Diagnostic assessment of psychotic disorders combined SCID-I interview and case note data. Prevalences of type 2 diabetes, adjusting for age and sex, were estimated by calculating predicted marginals. The prevalence estimate of type 2 diabetes was 22.0% among subjects with schizophrenia, 13.4% among subjects with other nonaffective psychosis and 6.1% in subjects without psychotic disorders. Only two subjects (3.4%) with affective psychosis had type 2 diabetes. Users of all types of antipsychotic medication had increased prevalence of type 2 diabetes. Our results suggest that type 2 diabetes is a major health concern among persons with schizophrenia and other nonaffective psychotic disorders and also in users of antipsychotic medication, but persons with affective psychosis in the general population may not have increased prevalence of type 2 diabetes.
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PMID:Type 2 diabetes among persons with schizophrenia and other psychotic disorders in a general population survey. 1799 51

Atypical antipsychotics are nowadays the most widely used drugs to treat schizophrenia and other psychosis. Unfortunately, some of them can cause major metabolic adverse effects, such as weight gain, dyslipidemia and type 2 diabetes. The underlying lipogenic mechanisms of the antipsychotic drugs are not known, but several studies have focused on a central effect in the hypothalamic control of appetite regulation and energy expenditure. In a functional convergent genomic approach we recently used a cellular model and demonstrated that orexigenic antipsychotics that induce weight gain activate the expression of lipid biosynthesis genes controlled by the sterol regulatory element-binding protein (SREBP) transcription factors. We therefore hypothesized that the major genes involved in the SREBP activation of fatty acids and cholesterol production (SREBF1, SREBF2, SCAP, INSIG1 and INSIG2) would be strong candidate genes for interindividual variation in drug-induced weight gain. We genotyped a total of 44 HapMap-selected tagging single nucleotide polymorphisms in a sample of 160 German patients with schizophrenia that had been monitored with respect to changes in body mass index during antipsychotic drug treatment. We found a strong association (P=0.0003-0.00007) between three markers localized within or near the INSIG2 gene (rs17587100, rs10490624 and rs17047764) and antipsychotic-related weight gain. Our finding is supported by the recent involvement of the INSIG2 gene in obesity in the general population and implicates SREBP-controlled lipogenesis in drug-induced metabolic adverse effects.
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PMID:Association between the insulin-induced gene 2 (INSIG2) and weight gain in a German sample of antipsychotic-treated schizophrenic patients: perturbation of SREBP-controlled lipogenesis in drug-related metabolic adverse effects? 1819 16

The frequency of obesity, insulin resistance, type 2 diabetes mellitus and other components of metabolic syndrome appear to be significantly elevated in some psychiatric patients. This is a notable example of genetic/environment interaction. Considering the genetic contribution, evidence of insulin resistance in persons with schizophrenia was reported in the pre-pharmacological era. High insulin, glucose, and cortisol levels are observed in first episode psychosis. The frequency of type 2 diabetes mellitus is significantly increased in persons with schizophrenia and bipolar disorder and in their first-degree relatives. Finally, a link exists between schizophrenia and enzymes involved in glycolysis and between antipsychotic drug-induced weight gain and serotonin receptor polymorphism. Important environmental factors are poor dietary habits, smoking, lack of physical exercise, and drug treatment, mostly with antipsychotic drugs (APDs) and perhaps with mood stabilizers. The APDs probably induce metabolic dysfunction by producing sudden appetite increase and weight gain in predisposed subjects. However, direct drug effects on glucose and lipid metabolism independent from body weight change have been proposed. Excessive weight gain is mainly observed with clozapine, olanzapine, chlorpromazine, and thioridazine and is less consistently noted with risperidone or quetiapine. Two recently introduced APDs, ziprasidone and aripiprazole, display a neutral effect on weight and metabolism. Subjects at high risk must be identified early during APD treatment so that provide lifestyle counseling and pharmacological assistance can be provided. The immediate research agenda for the APDs is to improve the animal models of drug-induced metabolic dysfunction; to clarify mechanisms other than weight gain and appetite stimulation; and to test pharmacological agents in randomized, double-blind studies to prevent or reverse metabolic syndrome in selected patients.
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PMID:The metabolic syndrome during atypical antipsychotic drug treatment: mechanisms and management. 1837 Jun 98

This final article presents the authors' recommendations, based on the findings presented in this publication, for clinical monitoring in patients being treated for mood and psychotic disorders. Suggestions are given for monitoring body weight/body mass index and for screening for type 2 diabetes and lipid abnormalities.
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PMID:Practical implications for clinical monitoring. 1966 58

The use of antipsychotic medications entails a difficult trade-off between the benefit of alleviating psychotic symptoms and the risk of troubling, sometimes life-shortening adverse effects. There is more variability among specific antipsychotic medications than there is between the first- and second-generation antipsychotic classes. The newer second-generation antipsychotics, especially clozapine and olanzapine, generally tend to cause more problems relating to metabolic syndrome, such as obesity and type 2 diabetes mellitus. Also, as a class, the older first-generation antipsychotics are more likely to be associated with movement disorders, but this is primarily true of medications that bind tightly to dopaminergic neuroreceptors, such as haloperidol, and less true of medications that bind weakly, such as chlorpromazine. Anticholinergic effects are especially prominent with weaker-binding first-generation antipsychotics, as well as with the second-generation antipsychotic clozapine. All antipsychotic medications are associated with an increased likelihood of sedation, sexual dysfunction, postural hypotension, cardiac arrhythmia, and sudden cardiac death. Primary care physicians should understand the individual adverse effect profiles of these medications. They should be vigilant for the occurrence of adverse effects, be willing to adjust or change medications as needed (or work with psychiatric colleagues to do so), and be prepared to treat any resulting medical sequelae.
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PMID:Adverse effects of antipsychotic medications. 2018 94

To examine the incidence of cardiometabolic conditions and change in care costs for patients with schizophrenia treated with antipsychotic medications, medical and pharmacy claims from the South Carolina Medicaid program were used to compare the incidence rates for five cardiometabolic conditions in 2,231 patients with schizophrenia who were newly prescribed one of seven antipsychotic medications, using a retrospective cohort design spanning three years. Incidence and cumulative prevalence (pre-existing + incident) rates for the five cardiometabolic conditions were: 10%/23.3% for Type II diabetes mellitus, 7%/13.3% for obesity/excessive weight gain, 17%/20.9% for dyslipidemia, 4.5%/7.3% for high blood pressure, and 15.6%/41.8% for hypertension. After being treated with the antipsychotic medications examined, the odds of developing obesity/excessive weight gain, Type II diabetes mellitus, or dyslipidemia were not significantly related to any specific atypical agent compared to haloperidol. Incidence rates for elevated blood pressure and clinically diagnosed hypertension were higher for patients prescribed ziprasidone (Odds Ratio [OR]=2.41, Confidence Intervals [CI]=1.20-4.85; OR=1.83, CI=1.16-2.90, respectively) relative to those prescribed haloperidol. Cost results indicate significant differences over time in medical service and pharmacy costs in the group which developed incident cardiometabolic conditions. Individuals diagnosed with schizophrenia with moderate prevalence and incidence rates for these cardiometabolic conditions demonstrated substantially decreasing medical care costs over the three years examined, perhaps indicating a widening gap in access to needed services for conditions that are known mortality risk factors.
Clin Schizophr Relat Psychoses 2010 Oct
PMID:Incidence and costs of cardiometabolic conditions in patients with schizophrenia treated with antipsychotic medications. 2145 40

Clozapine represents the treatment of choice for refractory psychosis, although a significant number of individuals demonstrate suboptimal response to it as well, leading to clozapine augmentation strategies. A variety of agents have been investigated in this regard, including mood stabilizers, such as anticonvulsants. Within this group of medications, topiramate is unique in that it is associated with weight loss, making it an attractive option because of clozapine's notable risk for associated metabolic disturbance. A 12-week naturalistic, open study was carried out to examine the potential benefits of topiramate in clozapine-treated individuals with schizophrenia demonstrating a suboptimal clinical response. We were specifically interested in clinical symptoms, changes in metabolic parameters, and tolerability. A total of 20 subjects were enrolled, and 16 completed the study, including 5 individuals with type 2 diabetes. Topiramate augmentation led to a 14% improvement in total Brief Psychiatric Rating Scale scores (P = 0.0003), a 2.5% decrease in body weight (P = 0.015), and was generally well tolerated, paraesthesia being the most common side effect. These findings support topiramate as a viable augmentation strategy in clozapine partial responders, with evidence of both clinical and metabolic benefits.
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PMID:Topiramate augmentation in clozapine-treated patients with schizophrenia: clinical and metabolic effects. 2110 86

Antipsychotic medications are associated with an increased risk of diabetes. Previous studies have also found an increased risk of type 2 diabetes mellitus in the relatives of schizophrenia probands. The aim of this study was to explore the metabolic adverse effects of olanzapine in a cohort of patients with newly diagnosed psychosis and minimal or no exposure to antipsychotics. Patients with newly diagnosed psychosis (n = 30) were enrolled in a 16-week open trial of olanzapine. Body mass index, fasting glucose, hemoglobin A1c, fasting insulin, IL-6, and a fasting lipid profile were measured at baseline and at 4-week intervals. There was a significant, linear increase over time in fasting glucose (P = 0.043), weight (P < 0.001), body mass index (P < 0.001), total cholesterol (P = 0.005), triglycerides (P = 0.003), and low-density lipoprotein (P = 0.013), but not hemoglobin A1c (P = 0.691), fasting insulin (P = 0.690), IL-6 (P = 0.877), or high-density lipoprotein (P = 0.446). An abnormal baseline IL-6 was a significant predictor of a greater increase in both total cholesterol (P < 0.01) and low-density lipoprotein (P < 0.01). Otherwise, neither parental history of type 2 diabetes mellitus nor baseline IL-6 predicted changes in metabolic measures. Changes in metabolic measures with olanzapine treatment can be detected early in the treatment of patients who are previously antipsychotic naive. The absence of a change in fasting insulin suggests a failure of pancreatic islet cells to compensate for the increase in fasting glucose.
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PMID:Metabolic effects of olanzapine in patients with newly diagnosed psychosis. 2134 17


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