Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type 2 diabetes mellitus and impaired glucose tolerance are associated with antipsychotic treatment. Risk factors for type 2 diabetes and impaired glucose tolerance include abdominal adiposity, age, ethnic status, and certain neuropsychiatric conditions. While impaired glucose metabolism was first described in psychotic patients prior to the introduction of antipsychotic medications, treatment with antipsychotic medications is associated with impaired glucose metabolism, exacerbation of existing type 1 and 2 diabetes, new-onset type 2 diabetes mellitus, and diabetic ketoacidosis, a severe and potentially fatal metabolic complication. The strength of the association between antipsychotics and diabetes varies across individual medications, with the largest number of reports for chlorpromazine, clozapine, and olanzapine. Recent controlled studies suggest that antipsychotics can impair glucose regulation by decreasing insulin action, although effects on insulin secretion are not ruled out. Antipsychotic medications induce weight gain, and the potential for weight gain varies across individual agents with larger effects observed again for agents like chlorpromazine, clozapine, and olanzapine. Increased abdominal adiposity may explain some treatment-related changes in glucose metabolism. However, case reports and recent controlled studies suggest that clozapine and olanzapine treatment may also be associated with adverse effects on glucose metabolism independent of adiposity. Dyslipidemia is a feature of type 2 diabetes, and antipsychotics such as clozapine and olanzapine have also been associated with hypertriglyceridemia, with agents such as haloperidol, risperidone, and ziprasidone associated with reductions in plasma triglycerides. Diabetes mellitus is associated with increased morbidity and mortality due to both acute (e.g., diabetic ketoacidosis) and long-term (e.g., cardiovascular disease) complications. A progressive relationship between plasma glucose levels and cardiovascular risk (e.g., myocardial infarction, stroke) begins at glucose levels that are well below diabetic or "impaired" thresholds. Increased adiposity and dyslipidemia are additional, independent risk factors for cardiovascular morbidity and mortality. Patients with schizophrenia suffer increased mortality due to cardiovascular disease, with presumed contributions from a number of modifiable risk factors (e.g., smoking, sedentary lifestyle, poor diet, obesity, hyperglycemia, and dyslipidemia). Patients taking antipsychotic medications should undergo regular monitoring of weight and plasma glucose and lipid levels, so that clinicians can individualize treatment decisions and reduce iatrogenic contributions to morbidity and mortality.
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PMID:Hyperglycemia and antipsychotic medications. 1180 85

Individuals with schizophrenia have standardised mortality rates which are double that of the general population. In addition to suicide, high rates of cardiovascular and respiratory disease contribute to this raised mortality rate. Although clozapine has been reported to improve psychotic symptoms and decrease suicide rates, attention has recently focussed on its potential to increase cardiovascular risk factors including obesity, dyslipidemia and diabetes mellitus. This study aimed to ascertain the prevalence of these risk factors in a cohort of Irish outpatients treated with clozapine.
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PMID:Prevalence of obesity, lipid and glucose abnormalities in outpatients prescribed clozapine. 1209 Apr 43

With the widespread use of atypical antipsychotics over the past several years, adverse metabolic effects have emerged as the most serious medical consequences of pharmacotherapy with some of these agents. Initially, weight gain and obesity were observed (especially with clozapine and olanzapine), but subsequently, type 2 diabetes and dyslipidemia became apparent as well. Further, many reports suggest that sudden and severe (occasionally fatal) diabetes ketoacidosis (DKA) can emerge during treatment with some atypical antipsychotics, even in the absence of adiposity. A marked increase of serum lipids (especially triglycerides) has also been reported, to varying degrees, with different atypicals. This article reviews the data regarding metabolic dysfunction in patients with psychosis (schizophrenia and bipolar disorder). Populations with psychosis have a 2-3-fold higher prevalence of diabetes even before treatment with any antipsychotics, suggesting a possible genetic linkage or comorbidity; this was confirmed with glucose regulation studies in schizophrenia and mania. The induction of type 2 diabetes with atypicals has further increased the prevalence of noninsulin-dependent diabetes from about 6% to 8% to 11% to 15% according to recent studies, and even higher rates of subclinical hyperglycemia. Serious weight gain (eg, 26-29 lbs after 1 year of clozapine or olanzapine treatment) is an important risk factor, but sudden DKA has now been reported in patients with minimal weight gain, suggesting alternative mechanisms, such as insulin resistance, as a direct effect of some atypicals. Psychiatrists can reduce the risk of metabolic disorders in schizophrenia and bipolar disorder by avoiding the use of certain atypicals as first-line treatment in patients with a personal or family history of diabetes, obesity, and hyperlipidemias. Regulatory agencies in some countries have already taken action in this regard.
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PMID:Factors in antipsychotic drug selection: tolerability considerations. 1497 55

The antipsychotic drugs (APDs) are fundamental tools in current psychiatric practice. A new generation of agents, the atypical APDs, represents an important progress in the treatment of psychotic disorders. Unfortunately, some of them induce excessive body weight gain (BWG), obesity, hyperglycemia and dyslipidemia in the following order: clozapine approximately equal to olanzapine > quetiapine > risperidone > ziprasidone = aripiprazole. Appetite stimulation is probably the main mechanism of BWG and this is strongly correlated with the APD affinity for H1 (histaminergic) and alpha1 (adrenergic) receptors. A composed ratio of the APD affinity for diverse neurotransmitters involved in food intake (FI) regulation correlates with BWG as well. Endocrine/metabolic mechanisms, such as the activation of the hypothalamus-pituitary-adrenal axis, changes in insulin sensitivity (by conventional and atypical agents), hyperprolactinemia and gonadal dysfunction (by conventional APDs and risperidone) may also be involved. Importantly, patients with schizophrenia may have a genetically-based predisposition to appetite dysregulation, insulin resistance and endocrine imbalance involving gonadal steroids. Excessive BWG must be prevented or attenuated by proper drug selection, combining or switching agents, nutritional assistance and physical exercise. Amantadine. metformin and reboxetine proved to significantly lessen APD-induced BWG. Notwithstanding this, novel strategies are necessary to treat this side effect in a clinical population particularly prone to poor compliance and under a high risk of negative drug interaction.
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PMID:Drug induced weight gain, an impediment to successful pharmacotherapy: focus on antipsychotics. 1505 13

The metabolic effect of atypical antipsychotic drugs may manifest itself in weight gain, disturbances in glucose homeostasis and dyslipidemia. One confounding factor is that psychotic disorders themselves make the patients prone to specific metabolic changes. Nevertheless clinical studies have confirmed that atypical anti-psychotic drugs have a different metabolic effect. In the present prospective case-series, four male antipsychotic drug-naive psychiatric patients without any familial history of metabolic disorder were studied. The patients received risperidone or olanzapine monotherapy for 12 weeks; weight, plasma levels of triglyceride, cholesterol, HDL, and fasting glucose were measured in every 4th week. In two patients, oral glucose tolerance test (OGTT) was also performed at days 0 and 56. The average weight gain during the 12-week period was 12%. The cholesterol and triglyceride plasma concentrations were also elevated. The fasting glucose levels did not change during the observation period. In the OGTT performed in two patients, normal fasting glucose and insulin plasma levels were observed after 8 weeks; however, the plasma insulin concentrations were highly elevated after glucose intake, which may suggest the presence of insulin resistance. Our preliminary results confirmed the previous results on the metabolic effect of atypical anti-psychotic drugs, which may lead to metabolic syndrome. The regular control of the metabolic laboratory parameters, early intervention and the modification of the atypical antipsychotic treatment may help to avoid this adverse effect of the drugs.
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PMID:[Effect of atypical antipsychotics on metabolism]. 1578 7

Olanzapine (Zyprexa, Eli Lilly & Co.) is an atypical antipsychotic medication with once-daily dosing that was originally developed for the treatment of schizophrenia. It has shown broad efficacy in the treatment of bipolar mixed and manic episodes, but is less effective in the treatment of bipolar depression. Double-blind studies have demonstrated a rapid onset of action in acute bipolar mania, significantly greater rates of response compared with placebo, and a remission rate of 88.3% in a 49-week open-label study. Diverse presentations of the illness responded well to olanzapine including patients with rapid-cycling bipolar disorder, mixed episodes, as well as psychotic and nonpsychotic manias. Olanzapine monotherapy improved symptoms of depression related to its sedating and appetite-enhancing profile, but core symptoms such as depressed mood did not improve significantly. However, in combination with fluoxetine, bipolar depressed patients responded without an increased risk of mania. Weight gain and sedation are prominent adverse effects, and it has been associated with atherogenic dyslipidemia and glucose intolerance.
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PMID:Use of olanzapine in the treatment of bipolar I disorder. 1585 3

Obesity and diabetes have caused problems for individuals with schizophrenia long before atypical antipsychotic agents. The prevalence of obesity, insulin resistance, impaired glucose tolerance, type 2 diabetes mellitus, dyslipidemia, and the Metabolic Syndrome has increased in people with schizophrenia as compared to the general population. Risk reduction studies for persons with obesity, diabetes, and cardiovascular disease indicate that cognitive/behavioral interventions that promote motivation and provide strategies to overcome the barriers in adherence to diet and activity modification are effective interventions for weight management and risk reduction. In the landmark multi-center randomized-controlled trial study, the Diabetes Prevention Project (DPP), a cognitive/behavioral intervention, was more successful in producing weight loss and preventing diabetes than the drugs metformin, troglitazone or placebo. This pilot study examined the effectiveness of a cognitive/behavioral group intervention, modified after the DPP program, in individuals with schizophrenia or schizoaffective disorder taking atypical antipsychotics in a large urban public mental health system. Outcome measures included body weight, body mass index, waist-hip ratios, and fasting glucose levels. Both groups demonstrated elevated fasting glucose levels and were obese with a mean BMI of 33. The group that received the cognitive/behavioral group intervention lost more weight than the treatment as usual group. The CB group participants lost an average of 5.4 lb or 2.9% of body weight, and those in the control group lost 1.3 lb or 0.6% body weight. The range of weight loss for the treatment group was from 1 to 20 lb. This pilot study has demonstrated that weight loss is possible with cognitive/behavioral interventions in a population with a psychotic disorder.
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PMID:A cognitive/behavioral group intervention for weight loss in patients treated with atypical antipsychotics. 1650 43

Reviews of the association between psychotic disorder, the metabolic syndrome, diabetes, and antipsychotic drugs conclude that there is a need for active, routine physical health screening of patients' prescribed antipsychotic drugs. From published guidelines, we derived the audit standard that all such patients should, as a minimum, have their blood pressure, body mass index (BMI) (or other measure of obesity such as waist circumference), blood glucose (or HbA(1c)), and plasma lipids measured at least once a year. We conducted an audit of the clinical records of 1966 eligible patients under the care of 48 multidisciplinary, assertive outreach clinical teams in 21 mental health services across the United Kingdom. This revealed a recorded measurement within the previous year for blood pressure in 26% of the patients, obesity in 17%, blood glucose (or HbA(1c)) in 28% and plasma lipids in 22%, with all 4 measures documented in 11%. In the total national sample, 6% had a documented diagnosis of diabetes, 6% hypertension, and 6% dyslipidemia. Extrapolating from the prevalence of these disorders in similar populations suggests that for every patient with a known diagnosis of diabetes, another had not been recognized, for every known case of hypertension, 4 had been missed, and for every known case of dyslipidemia, 7 had been missed. The responses of the clinical teams to a questionnaire yielded information on obstacles to screening in routine practice, revealing uncertainty about whose responsibility this was, a lack of confidence about the interpretation of abnormal screening results, and limited access to basic equipment.
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PMID:A UK audit of screening for the metabolic side effects of antipsychotics in community patients. 1748 1

Statins are widely used in the treatment of patients having high levels of serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). However, there is little documentation on the ability of statins to treat dyslipidemia induced by second-generation antipsychotics (SGAs) and if so, to what extent. A goal of the present study was to evaluate these aspects among psychotic inpatients who were prescribed SGAs in a typical clinical setting. The study sample consisted of 28 psychotic male forensic psychiatric inpatients (mean age 44 years). All had sGA medication for their psychotic symptoms. secondary causes of dyslipidemia were excluded and statin therapy was initiated, according to the established guidelines. The change in TC, LDL-C, high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) levels were evaluated retrospectively and analysed by the Wilcoxon signed Ranks test. The lowering effectivity of statin treatment was 36% for TC, 49% for LDL-C and 29% for TG. Most of the patients (84%) achieved a target value for LDL-C of <3.0 mmol/L, and 54% achieved target value of <2.6 mmol/L, while HDL-C remained unchanged. These results were achieved with a low or moderate dose of statin during a period of 1 month. The effect of statins in lowering of TC, LDL-C and TG among dyslipidemic psychiatric patients that were treated with sGA was similar to the effectiveness of statin therapy in other clinical trial settings, and should be used when they are indicated.
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PMID:Statins are effective in treating dyslipidemia among psychiatric patients using second-generation antipsychotic agents. 1771 4

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


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