scholarly journals A Focused Review of the Metabolic Side-Effects of Clozapine

2021 ◽  
Vol 12 ◽  
Author(s):  
Jessica W. Y. Yuen ◽  
David D. Kim ◽  
Ric M. Procyshyn ◽  
William J. Panenka ◽  
William G. Honer ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Side Effects ◽  
Plasma Lipids ◽  
Treatment Options ◽  
Metabolic Effects ◽  
Future Research ◽  
Metabolic Dysregulation ◽  
The Metabolic Syndrome ◽  
Metabolic Side Effects ◽  
Biological Substrates

The second generation antipsychotic drug clozapine represents the most effective pharmacotherapy for treatment-resistant psychosis. It is also associated with low rates of extrapyramidal symptoms and hyperprolactinemia compared to other antipsychotic drugs. However, clozapine tends to be underutilized in clinical practice due to a number of disabling and serious side-effects. These are characterized by a constellation of metabolic side-effects which include dysregulation of glucose, insulin, plasma lipids and body fat. Many patients treated with clozapine go on to develop metabolic syndrome at a higher rate than the general population, which predisposes them for Type 2 diabetes mellitus and cardiovascular disease. Treatments for the metabolic side-effects of clozapine vary in their efficacy. There is also a lack of knowledge about the underlying physiology of how clozapine exerts its metabolic effects in humans. In the current review, we focus on key studies which describe how clozapine affects each of the main symptoms of the metabolic syndrome, and cover some of the treatment options. The clinical data are then discussed in the context of preclinical studies that have been conducted to identify the key biological substrates involved, in order to provide a better integrated overview. Suggestions are provided about key areas for future research to better understand how clozapine causes metabolic dysregulation.

The Role of Atypical Antipsychotics in Glucose/Insulin Dysregulation and the Evolving Role of the Psychiatrist in a New Era of Drug Treatment Options

CNS Spectrums ◽  
2004 ◽  
Vol 9 (11) ◽  
pp. 849-861 ◽  
Author(s):  
Anthony Ferraioli ◽  
Kara Lee Shirley ◽  
Panakkal David
Keyword(s):  
Metabolic Syndrome ◽  
Atypical Antipsychotics ◽  
Treatment Options ◽  
Metabolic Effects ◽  
Drug Induced ◽  
New Era ◽  
Metabolic Dysregulation ◽  
The Metabolic Syndrome ◽  
Glucose Dysregulation

ABSTRACTThis article examines the issue of atypical antipsychotics, glucose/insulin, and other metabolic derangements (ie, metabolic syndrome), including a general introduction to the health, concerns of our patients, a review of the literature, possible mechanisms of antipsychotic induced glucose dysregulation, monitoring approaches, and management and prevention of metabolic syndrome. Literature review leads to mechanism hypotheses and risk estimations, leading to guidelines for monitoring and treatment. The patient population suffers from a higher degree of baseline metabolic dysregulation resulting in cardiovascular disease through components of the metabolic syndrome, and this risk increases with administration of atypical antipsychotic medication at different rates, depending on both drug and patient risk factors. The growing knowledge of mechanisms behind drug induced glucose/insulin and other metabolic dysregulation, as well as advances in pharmacogenomics, will help refine drug selection and monitoring for adverse, life-threatening metabolic effects.

Complement Components, C3 and C4, and the Metabolic Syndrome

2018 ◽  
Vol 15 (1) ◽  
pp. 44-48 ◽  
Author(s):  
Melanie Copenhaver ◽  
Chack-Yung Yu ◽  
Robert P. Hoffman
Keyword(s):  
Metabolic Syndrome ◽  
Significant Role ◽  
Complement System ◽  
Gene Copy ◽  
Future Research ◽  
Obese Adults ◽  
Complement Components ◽  
Cardiometabolic Diseases ◽  
The Metabolic Syndrome ◽  
The Complement System

Introduction: Increased systemic inflammation plays a significant role in the development of adult cardiometabolic diseases such as insulin resistance, dyslipidemia, atherosclerosis, and hypertension. The complement system is a part of the innate immune system and plays a key role in the regulation of inflammation. Of particular importance is the activation of complement components C3 and C4. C3 is produced primarily by the liver but is also produced in adipocytes, macrophages and endothelial cells, all of which are present in adipose tissues. Dietary fat and chylomicrons stimulate C3 production. Adipocytes in addition to producing C3 also have receptors for activated C3 and other complement components and thus also respond to as well as produce a target for complement. C3adesArg, also known as acylation stimulation factor, increases adipocyte triglyceride synthesis and release. These physiological effects play a significant role in the development of metabolic syndrome. Epidemiologically, obese adults and non-obese adults with cardiometabolic disease who are not obese have been shown to have increased complement levels. C4 levels also correlate with body mass index. Genetically, specific C3 polymorphisms have been shown to predict future cardiovascular events and. D decreased C4 long gene copy number is associated with increased longevity. Conclusion: Future research is clearly needed to clarify the role of complement in the development of cardiovascular disease and mechanisms for its action. The complement system may provide a new area for intervention in the prevention of cardiometabolic diseases.

Abstract 369: Naringenin Supplementation to a Chow Diet Reduces Plasma Lipids and Adiposity, and Suppresses Rer In Ldlr -/- Mice Fed a Chow Diet

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Amy C Burke ◽  
Dawn E Telford ◽  
Brian G Sutherland ◽  
Jane Y Edwards ◽  
Murray W Huff
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
White Adipose Tissue ◽  
Plasma Lipids ◽  
Metabolic Effects ◽  
Chow Diet ◽  
Light Cycle ◽  
Ambulatory Activity ◽  
Metabolic Dysregulation

Previously, we have shown that intervention by the addition of the citrus flavonoid naringenin to a chow diet enhances the reversal of diet-induced metabolic dysregulation, obesity, and atherosclerosis. However, the metabolic effects of naringenin in the absence of obesity and metabolic dysregulation are unknown. In the present study, we assessed the effect of naringenin supplementation to a chow diet on plasma lipids, adiposity, respiratory exchange ratio (RER), ambulatory activity and tissue lipolysis. For 8 weeks, Ldlr -/- mice were fed an isoflavone-free chow diet supplemented with or without 3% naringenin. Over 8 weeks, there was no difference in caloric intake between the two groups. Naringenin supplementation reduced plasma VLDL-cholesterol (C) (-46%; P <0.05), VLDL-triglycerides (-43%; P <0.05), and LDL-C (-27%; P <0.05) compared to mice consuming chow alone. Chow-fed mice maintained body weight, whereas mice fed chow with naringenin were ~1.4 g lighter ( P <0.05) with significantly reduced adiposity (-48%; P <0.05). Histological analysis of epididymal white adipose tissue showed naringenin supplementation reduced adipocyte size and number. Between 6 and 8 weeks of diet, mice were assessed in metabolic cages. Naringenin supplementation had no effect on food intake, ambulatory activity or energy expenditure during both the light and dark cycles. Consistently, naringenin-treated mice had significantly lower RER compared to mice fed chow alone (0.97 vs 0.99; P <0.05). This difference was driven by a significant suppression in RER during the light cycle (0.96 vs 1.00; P <0.05), but not the dark cycle (0.97 vs 0.98 N.S ), suggesting an enhanced starvation response. Triglyceride lipolysis was highest in white adipose tissue, followed by liver and muscle. Naringenin supplementation to chow increased the lipolytic rate in adipose, but not in muscle or liver, suggesting reduced adiposity was related to increased expression of ATGL or HSL. In conclusion, compared to chow alone, naringenin supplementation reduced plasma lipids and decreased body weight via increased adipose tissue lipolysis and suppressed RER, with no change in energy expenditure.

Abstract 1186: Overexpression Of Endothelial Lipase In The Liver Promotes The Clearance Of Plasma Lipids But Accelerates Liver Steatosis In A Mouse Model Of Metabolic Syndrome

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Tomoyuki Yasuda ◽  
Tatsuro Ishida ◽  
Yoko Kojima ◽  
Hanayo Tanaka ◽  
Takeaki Okada ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Fatty Acid ◽  
Mouse Model ◽  
Fatty Acid Synthase ◽  
Plasma Lipids ◽  
Recombinant Adenovirus ◽  
Mrna Level ◽  
Liver Steatosis ◽  
Endothelial Lipase ◽  
The Metabolic Syndrome

The metabolic syndrome includes high triglyceride (TG) and low HDL-cholesterol (HDL-C) levels in the plasma, and often accompanies steatosis in the liver. Endothelial lipase (EL) is a phospholipase that regulates HDL metabolism. EL is expressed by hepatocytes, while the function of EL in the liver has not been identified. Here, we examined the role of EL in the liver using a mouse model of metabolic syndrome. The EL expression in the liver was analyzed by real-time PCR. It revealed that liver EL expression was significantly increased in obese and diabetic db/db mice compared to that of control mice. To examine the significance of the EL upregulation in the liver, we injected the recombinant adenovirus encoding human EL into mice. The EL overexpression in the liver resulted in a significant decrease in plasma HDL-C, TG, and free fatty acid levels. Interestingly, the EL overexpression in the liver increased liver weight and liver TG content both in wild-type and db/db mice. In db/db mice, particularly, EL overexression accelerated the formation of steatosis by increasing the mRNA level of fatty acid synthase. These findings indicate that EL expression is increased in the liver in the metabolic syndrome. The upregulation of EL promotes the uptake of plasma lipids by hepatocytes, and accelerates the progression of steatosis in db/db mice. Thus EL may play a role in the genesis of steatosis as well as dyslipidemia in the metabolic syndrome.

Anti-Inflammatory Effects of Exercise on Metabolic Syndrome Patients: A Systematic Review and Meta-Analysis

2020 ◽  
pp. 109980042095806 ◽  
Author(s):  
Heidar Alizaei Yousefabadi ◽  
Arghavan Niyazi ◽  
Sahar Alaee ◽  
Mehrdad Fathi ◽  
Gholam Rasul Mohammad Rahimi
Keyword(s):  
Metabolic Syndrome ◽  
Exercise Training ◽  
Inflammatory Markers ◽  
Meta Analysis ◽  
Serum Levels ◽  
Future Research ◽  
The Metabolic Syndrome ◽  
Inflammatory Status ◽  
Tnf Α ◽  
Training Impact

Background: Increments in inflammatory indicators and low levels of physical activity are correlated to the expansion of the metabolic syndrome (MetS). Objective: The purpose of this study was to establish if exercise training ameliorates inflammatory status in MetS patients. Data sources: PubMed, CINAHL, and Medline, Google Scholar, and Scopus databases and reference lists of included studies were searched. Study selection: Twenty randomized controlled trials (RCTs) of exercise-training impact on inflammatory markers (tumor necrosis factor (TNF) α, C-reactive protein (CRP), interleukin (IL) 6, IL-8, IL-10, and IL-18) with concurrent control groups were included in this analysis. Results: Results demonstrated an overall significant decrease in serum levels of TNF-α (mean difference (MD): −1.21 pg/ml; 95% confidence interval (CI): −1.77, −0.66), CRP (MD: −0.52 mg/l; 95% CI: −0.79, −0.25), IL-8 (MD: −1.31 pg/ml; 95% CI: −2.57, −0.06), and a significant increase in IL-10 (MD: 0.48 pg/ml; 95% CI: 0.10, 0.86). But exercise training did not change the level of IL-6 (MD: −0.69 pg/ml; 95% CI: −1.53, 0.14) and IL-18 (MD: −53.01 pg/ml; 95% CI: −166.64, 60.62). Conclusion: Exercise training improves TNF-α, CRP, IL-8, and IL-10 levels in patients with MetS. For some variables, isolated aerobic exercise, and combined aerobic and resistance exercise appears to be optimal. Future research is needed to clarify the mechanisms underlying exercise training’s effect on this population’s inflammatory markers. More studies are required to confirm these findings.

scholarly journals Antidiabetic Effects of Bisamide Derivative of Dicarboxylic Acid in Metabolic Disorders

2020 ◽  
Vol 21 (3) ◽  
pp. 991 ◽  
Author(s):  
Angelina Vladimirovna Pakhomova ◽  
Vladimir Evgenievich Nebolsin ◽  
Olga Victorovna Pershina ◽  
Vyacheslav Andreevich Krupin ◽  
Lubov Alexandrovna Sandrikina ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Stem Cells ◽  
Dicarboxylic Acid ◽  
Metabolic Disorders ◽  
Biological Effects ◽  
Treatment Options ◽  
The Metabolic Syndrome ◽  
Pancreatic Stem Cells ◽  
The Impact

In clinical practice, the metabolic syndrome can lead to multiple complications, including diabetes. It remains unclear which component of the metabolic syndrome (obesity, inflammation, hyperglycemia, or insulin resistance) has the strongest inhibitory effect on stem cells involved in beta cell regeneration. This makes it challenging to develop effective treatment options for complications such as diabetes. In our study, experiments were performed on male C57BL/6 mice where metabolic disorders have been introduced experimentally by a combination of streptozotocin-treatment and a high-fat diet. We evaluated the biological effects of Bisamide Derivative of Dicarboxylic Acid (BDDA) and its impact on pancreatic stem cells in vivo. To assess the impact of BDDA, we applied a combination of histological and biochemical methods along with a cytometric analysis of stem cell and progenitor cell markers. We show that in mice with metabolic disorders, BDDA has a positive effect on lipid and glucose metabolism. The pancreatic restoration was associated with a decrease of the inhibitory effects of inflammation and obesity factors on pancreatic stem cells. Our data shows that BDDA increases the number of pancreatic stem cells. Thus, BDDA could be used as a new compound for treating complication of the metabolic syndrome such as diabetes.

scholarly journals Ranking Self-reported Gastrointestinal Side Effects of Pharmacotherapy in Sarcoidosis

Lung ◽  
2020 ◽  
Vol 198 (2) ◽  
pp. 395-403 ◽  
Author(s):  
M. Drent ◽  
V. L. J. Proesmans ◽  
M. D. P. Elfferich ◽  
N. T. Jessurun ◽  
S. M. G. de Jong ◽  
...  
Keyword(s):  
Weight Gain ◽  
Side Effects ◽  
Side Effect ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Future Research ◽  
Dietary Interventions ◽  
Cross Sectional ◽  
Organ Systems ◽  
Gastrointestinal Side Effects

Abstract Background Clinical manifestations of sarcoidosis vary widely, depending on the intensity of the inflammation and the organ systems affected. So far, no curative treatment exists; the disease can only be suppressed. All treatment options cause side effects affecting quality of life. The aim of this study was to establish and rank the prevalence of self-reported gastrointestinal side effects of drugs used in the treatment of sarcoidosis. Methods A cross-sectional web-based anonymous survey about complaints and side effects was conducted among sarcoidosis patients in the Netherlands, United Kingdom, and United States of America. Results Of the participants, 70% were being treated with one or more drugs. The most important reported side effect was weight gain, associated with increased appetite among prednisone users (as monotherapy as well as in combination with other drugs). Methotrexate (MTX) users especially experienced nausea, with monotherapy as well as combination therapy. Vomiting and weight loss were most prominent among azathioprine and mycophenolate mofetil (MMF) users, whereas diarrhoea was frequently mentioned by MMF and MTX users. The reported side effects of hydroxychloroquine were generally rather mild. Conclusion The current study ranked the gastrointestinal side effects associated with pharmacotherapy in sarcoidosis patients. Pharmacotherapy does have multiple gastrointestinal side effects. The strongest association between a reported side effect and drug use was that of weight gain associated with increased appetite among prednisone users. It would therefore be useful for future research to look further into dietary interventions to counter these side effects and reduce their burden.

Metabolic dysregulation and late-life depression: a prospective study

2016 ◽  
Vol 47 (6) ◽  
pp. 1041-1052 ◽  
Author(s):  
R. M. Marijnissen ◽  
N. Vogelzangs ◽  
M. E. Mulder ◽  
R. H. S. van den Brink ◽  
H. C. Comijs ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Waist Circumference ◽  
Depressive Symptomatology ◽  
Hdl Cholesterol ◽  
Late Life ◽  
Late Life Depression ◽  
Metabolic Dysregulation ◽  
The Metabolic Syndrome ◽  
Co Morbidity ◽  
Severity Of Depression

BackgroundDepression is associated with the metabolic syndrome (MS). We examined whether metabolic dysregulation predicted the 2-year course of clinical depression.MethodA total of 285 older persons (⩾60 years) suffering from depressive disorder according to DSM-IV-TR criteria was followed up for 2 years. Severity of depression was assessed with the Inventory of Depressive Symptomatology (IDS) at 6-month intervals. Metabolic syndrome was defined according the National Cholesterol Education Programme (NCEP-ATP III). We applied logistic regression and linear mixed models adjusted for age, sex, years of education, smoking, alcohol use, physical activity, somatic co-morbidity, cognitive functioning and drug use (antidepressants, anti-inflammatory drugs) and severity of depression at baseline.ResultsMS predicted non-remission at 2 years (odds ratioper component = 1.26, 95% confidence interval 1.00–1.58), p = 0.047), which was driven by the waist circumference and HDL cholesterol. MS was not associated with IDS sum score. Subsequent analyses on its subscales, however, identified an association with the somatic symptom subscale score over time (interaction time × somatic subscale, p = 0.005), driven by higher waist circumference and elevated fasting glucose level.ConclusionsMetabolic dysregulation predicts a poor course of late-life depression. This finding supports the concept of ‘metabolic depression’, recently proposed on population-based findings of a protracted course of depressive symptoms in the presence of metabolic dysregulation. Our findings seem to be driven by abdominal obesity (as indicated by the waist circumference) and HDL cholesterol dysregulation.

Pre- and early postnatal nongenetic determinants of type 2 diabetes

2002 ◽  
Vol 4 (24) ◽  
pp. 1-14 ◽  
Author(s):  
Susan E. Ozanne ◽  
C. Nick Hales
Keyword(s):  
Gene Expression ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Hormone Receptors ◽  
Early Growth ◽  
Growth Restriction ◽  
Future Research ◽  
Thrifty Phenotype ◽  
The Metabolic Syndrome

Epidemiological studies have revealed strong and internationally reproducible links between early growth restriction and subsequent risk of developing type 2 diabetes and the metabolic syndrome (glucose intolerance, hypertension and hypertriglyceridaemia). This effect can exist independently of genetic factors. There is also direct evidence that poor maternal nutrition and maternal smoking cause both a reduction in birthweight and subsequent loss of glucose tolerance. High rates of growth in childhood may add to these effects. The ‘thrifty phenotype’ hypothesis attempts to explain these associations in terms of an altered programming of growth and metabolism that aids survival both pre- and postnatally. Type 2 diabetes is envisaged as a consequence of a clash of this programming with adult obesity. Tests of this hypothesis in animal models have shown that both the metabolic syndrome and type 2 diabetes can result from early growth restriction in rats consequent upon rat dams being fed a reduced protein, isocaloric diet (in which the protein is replaced by an equal quantity of nonprotein energy). A variety of other models of early growth restriction in rats lead to a similar phenotype. Several structural and gene expression changes have been shown in many tissues, including pancreas, liver, kidney, muscle and adipose tissue. Changes in gene expression include those concerned with hormone receptors, signalling and glycolytic enzymes. Many important questions remain for future research.

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