Pre-existing Metabolic Abnormalities Research Articles

Metabolic complications of psychotropic medications in psychiatric disorders: Emerging role of de novo lipogenesis and therapeutic consideration.

Although significant advances have been made in understanding the patho-physiology of psychiatric disorders (PDs), therapeutic advances have not been very convincing. While psychotropic medications can reduce classical symptoms in patients with PDs, their long-term use has been reported to induce or exaggerate various pre-existing metabolic abnormalities including diabetes, obesity and non-alcoholic fatty liver disease (NAFLD). The mechanism(s) underlying these metabolic abnormalities is not clear; however, lipid/fatty acid accumulation due to enhanced de novo lipogenesis (DNL) has been shown to reduce membrane fluidity, increase oxidative stress and inflammation leading to the development of the aforementioned metabolic abnormalities. Intriguingly, emerging evidence suggest that DNL dysregulation and fatty acid accumulation could be the major mechanisms associated with the development of obesity, diabetes and NAFLD after long-term treatment with psychotropic medications in patients with PDs. In support of this, several adjunctive drugs comprising of anti-oxidants and anti-inflammatory agents, that are used in treating PDs in combination with psychotropic medications, have been shown to reduce insulin resistance and development of NAFLD. In conclusion, the above evidence suggests that DNL could be a potential pathological factor associated with various metabolic abnormalities, and a new avenue for translational research and therapeutic drug designing in PDs.

COVID-19 and its impact on neurological manifestations and mental health: the present scenario.

Though the COVID-19 pandemic primarily affects pulmonary and cardiorenal functions, many healthcare and its allied groups reported neurological involvement of SARS-CoV-2 in combination with either pre-existing metabolic abnormalities, medical conditions, infections or even chronic to acute inflammatory episodes of the nervous system. The present review provides a fair outlook of the published literature and also the case reports with an emphasis on plausible mechanisms involved in neurological complications of the central and peripheral nervous systems. Awareness on the neuropsychiatric manifestations being discussed in this article should ideally help the medical community in early identification and effective management of potentially life-threatening neurological diseases.

A metabolic handbook for the COVID-19 pandemic.

For infectious-disease outbreaks, clinical solutions typically focus on efficient pathogen destruction. However, the COVID-19 pandemic provides a reminder that infectious diseases are complex, multisystem conditions, and a holistic understanding will be necessary to maximize survival. For COVID-19 and all other infectious diseases, metabolic processes are intimately connected to the mechanisms of disease pathogenesis and the resulting pathology and pathophysiology, as well as the host defence response to the infection. Here, I examine the relationship between metabolism and COVID-19. I discuss why preexisting metabolic abnormalities, such as type 2 diabetes and hypertension, may be important risk factors for severe and critical cases of infection, highlighting parallels between the pathophysiology of these metabolic abnormalities and the disease course of COVID-19. I also discuss how metabolism at the cellular, tissue and organ levels might be harnessed to promote defence against the infection, with a focus on disease-tolerance mechanisms, and speculate on the long-term metabolic consequences for survivors of COVID-19.

Correction: Effects of Low Dose Metformin on Metabolic Traits in Clozapine-Treated Schizophrenia Patients: An Exploratory Twelve-Week Randomized, Double-Blind, Placebo-Controlled Study

[This corrects the article DOI: 10.1371/journal.pone.0168347.].

Effects of Low Dose Metformin on Metabolic Traits in Clozapine-Treated Schizophrenia Patients: An Exploratory Twelve-Week Randomized, Double-Blind, Placebo-Controlled Study.

BackgroundMetformin has been used for alleviating metabolic abnormalities in patients with schizophrenia. The lowest dose of metformin to treat metabolic abnormalities in clozapine-treated patients is 1000 mg/d. This study was designed to determine whether metformin at 500 mg/d and 1000 mg/d is effective in improving the metabolic profiles of clozapine-treated patients with pre-existing metabolic abnormalities, and whether its effectiveness depends on metformin dosage.MethodsIn this 12-week, randomized, double-blind, placebo-controlled trial, metformin at 500 mg/d or 1000 mg/d was prescribed to clozapine-treated patients with schizophrenia who had pre-existing metabolic abnormalities. The recruited patients underwent physical and laboratory evaluations at weeks 4, 8, and 12. The outcomes were any changes in metabolic traits.ResultsAmong the 96 clozapine-treated patients with schizophrenia screened for the trial, 55 patients with pre-existing metabolic abnormalities were randomly assigned to placebo (n = 18), metformin dosage at 500 mg/d (n = 18), and metformin dosage at 1000 mg/d (n = 19) groups. The body weight (BW) of patients in the metformin 1000 mg/d group significantly decreased, by a mean of 0.97 kg over the 12 week trial period. Moreover, patients in the metformin at 500 mg/d and 1000 mg/d groups had a significant decrease in body mass index (BMI) after 12 weeks, with the mean decrease being 0.70 and 0.50 kg/m2, respectively. No significant changes were observed in the other metabolic parameters of patients in the three groups.ConclusionsOur results demonstrated that a low metformin dosage of either 500 mg/d or 1000 mg/d for 12 weeks slightly reduced the BW and BMI of clozapine-treated patients with pre-existing metabolic abnormalities. A longer period of treatment with a larger sample is warranted to determine the factors that influence the metformin treatment response.Trial RegistrationClinicalTrials.gov NCT02751307

Effects of Adjunctive Metformin on Metabolic Traits in Nondiabetic Clozapine-Treated Patients With Schizophrenia and the Effect of Metformin Discontinuation on Body Weight

Many studies have shown that metformin can decrease body weight and improve metabolic abnormalities in patients with schizophrenia. Whether or not the beneficial effects can be sustained after discontinuation of metformin needs to be evaluated. We conducted a 24-week randomized, double-blind, placebo-controlled study to evaluate the effect of metformin on metabolic features in clozapine-treated patients with schizophrenia and followed their body weight after stopping the intervention for at least 24 weeks. The study was conducted between September 2008 and July 2011. We recruited patients with DSM-IV diagnosis of schizophrenia or schizoaffective disorder who had been taking clozapine for more than 3 months, were overweight or obese, or fulfilled at least 1 criteria of metabolic syndrome. Eligible patients were randomized to receive metformin 1,500 mg/d or placebo. We followed metabolic features at baseline and at weeks 2, 4, 8, 16, and 24 and rechecked body weight when the patients stopped the trial after at least 24 weeks. A total of 55 subjects (28 in the metformin and 27 in the placebo group) were enrolled. There were no significant differences in all baseline characteristics between the 2 groups, except that patients in the metformin group had higher fasting plasma glucose levels (P = .03). After the 24-week intervention, body weight (P < .0001), body mass index (P < .0001), fasting plasma glucose (P < .0001), high-density lipoprotein cholesterol (P = .03), insulin level (P = .01), and homeostasis model assessment index (P = .02) had significant changes in the metformin group. At the end of the intervention, 8 patients (28.57%) lost more than 7% of their body weight in the metformin group. Mean body weight returned to baseline after patients stopped the intervention in the metformin group. Metformin can significantly reduce body weight and reverse metabolic abnormalities in clozapine-treated patients with schizophrenia and preexisting metabolic abnormalities. However, the beneficial effects of metformin on body weight disappeared after discontinuing this medication.

The Effects of Sucrose on Metabolic Health: A Systematic Review of Human Intervention Studies in Healthy Adults

We systematically reviewed interventions substituting sucrose for other macronutrients in apparently healthy adults to assess impact on cardiometabolic risk indicators. Multiple databases were searched to January 2012 and abstracts assessed by 2 reviewers. Twenty-five studies (29 papers) met inclusion criteria but varied in quality and duration. Weaknesses included small subject numbers, unclear reporting of allocation, unusual dietary regimes, differences in energy intake, fat composition or fibre between conditions, unhealthy subjects, heterogeneity of results, and selective reporting. Insufficient data were available to draw reliable conclusions except with regard to the substitution of sucrose for starch, where effects on plasma lipids were inconsistent, mostly explicable by other factors, or nonsignificant. Based on fewer studies, there was little evidence for significant effects on plasma glucose or insulin. Sucrose substitution for starch up to 25% energy does not appear to have adverse effects on cardiometabolic risk indicators in apparently healthy adults. Furthermore, there is no consistent evidence that restricting sucrose in an isoenergetic diet would affect risk indicators, except perhaps in people with certain preexisting metabolic abnormalities. Larger, high-quality studies, lasting several months and studying a wider range of outcomes, are needed in order to provide evidence on which to base public health initiatives.

Intracranial calcification in a uremic infant with Wilms' tumor in a solitary kidney.

Wilms' tumor (WT), also called nephroblastoma, is an embryonic neoplasm of the developing kidney. A previously healthy Japanese female infant had WT in a single kidney without associated congenital malformations. Preoperative chemotherapy was started for the preservation of renal tissue and function. Tumor lysis syndrome, disseminated intravascular coagulopathy, and acute renal failure were accompanying. The infant needed surgical intervention and permanent replacement therapy. At the start of emergency hemodialysis, the infant had posterior reversible leukoencephalopathy syndrome because of severe hypertension. During ongoing peritoneal dialysis, the infant suffered from anemia, dietary and fluid restriction, and restriction of time and mobility. Despite alfacalcidol and calcium supplementation, the infant had secondary hyperparathyroidism and remarkably short stature. After waiting for the completion of chemotherapy, renal transplantation from the mother was completed. Successful kidney transplantation promptly corrected preexisting metabolic abnormalities causing secondary hyperparathyroidism. Subsequently, the infant often complained of headache. Computed tomographic scanning revealed calcification in the cerebellum. Refractory secondary hyperparathyroidism was inferred as the cause. A well-functioning graft provided the infant with a greater sense of well-being and enabled her to enjoy a lifestyle free of dialysis, although the infant must continue taking transplant medications and has retained unresolved issues of short stature and ectopic intracranial calcification.

Olanzapine: interpreting the label change

Olanzapine: interpreting the label change

Pharmacist involvement in a rapid-response team at a community hospital

In hospital cardiac arrest is associated with high mortality rates.[1][1] Many patients who suffer cardiac arrest or pulmonary arrest have preexisting respiratory or metabolic abnormalities and clinical deterioration.[2][2] Risk factors for avoidable inhospital cardiac arrests include abnormal

Cardiovascular disease after renal transplantation

Cardiovascular disease is a major hazard limiting the life expectancy of renal transplant recipients and the most frequent cause of late allograft loss. Patients with renal disease have usually been exposed for both traditional, and for them unique, risk factors over a prolonged period of time and may carry the burden of advanced atherosclerotic disease already at the time of transplantation. The observed survival benefit of transplantation is probably from elimination of the numerous uremia-related risk factors. However, immunosuppressive therapy and the chronic inflammatory state, together with genetic susceptibility and not infrequently impaired renal function, may bring about new potentially atherogenic conditions. Metabolic risk factors may jeopardize both patient and graft survival. Several observational studies provide evidence for the negative impact of preexisting metabolic abnormalities on long-term outcomes. Identification of modifiable cardiovascular risk factors may enable risk reduction also in renal transplant recipients. Results of ongoing intervention trials are awaited. The observed improvement of patient survival after renal transplantation during the past decade may reflect the increasing awareness and more optimal care of patients throughout the course of renal disease.

Non-Alcoholic Steatohepatitis: Clinical Significance and Pathogenesis

Non-alcoholic steatohepatitis (NASH) is a form of liver disease resembling alcoholic liver disease in a patient who does not consume significant amounts of alcohol. Since its first description in 1980 it has been recognized with increasing frequency. The natural course is relatively benign, but liver cirrhosis, together with all its sequelae, may develop; sometimes liver transplantation is indicated. NASH should probably be regarded as a two-stage acquired metabolic disorder consisting of the development of the insulin resistance syndrome in a patient with pre-existing metabolic abnormalities. The insulin resistance syndrome may well be the most important metabolic abnormality giving rise to hepatic steatosis. The preexisting metabolic abnormalities can be diverse, and may well be multifactorial and/or polymorphogenetic. A steatotic liver may be more susceptible to the deleterious effects of the pre-existing metabolic abnormalities. Pre-existing metabolic abnormalities of particular interest are increased hepatic iron storage and derangements of lipoprotein metabolism. While awaiting the complete resolution of the pathogenesis, current treatment is largely conservative. Every patient should be encouraged to lose weight and to avoid alcohol and other hepatotoxins. In addition, diabetes, lipid abnormalities and increased iron stores should be looked for.

Metabolic effects of estrogens and progestins

To review the effects of exogenous estrogen and progestin on metabolic risk factors for coronary artery disease in women.Review of selected literature.Population studies and clinical trials.Premenopausal and postmenopausal women.Exogenous gonadal hormones in oral contraceptives and hormone replacement regimens.Lipoprotein, hemostatic, carbohydrate, and blood pressure metabolic parameters.Favorable lipoprotein changes have been demonstrated in both observational studies and clinical trials of effects of exogenous hormones on cardiovascular risk factors in women. These include declines in low-density lipoprotein, apoprotein B, and lipoprotein(a), and increases in high-density lipoprotein (HDL), HDL2, and apoprotein A-I. Hormone replacement effects on triglyceride are minor and, in most patients, probably benign. Evidence is unconvincing that clinically significant changes in clotting factors, carbohydrate metabolism, or blood pressure take place as a result of postmenopausal hormone interventions. In fact, carbohydrate metabolism and blood pressure may be improved slightly. Metabolic studies do not, thus far, provide any contraindications to either estrogen replacement therapy (ERT) or hormone replacement therapy (HRT) in appropriately selected subjects. However, because studies of metabolic risk factors generally have been done in patients who were not hyperlipidemic, hypercoagulable, hyperglycemic, or hypertensive, little is known about the metabolic effects of ERT or HRT on pre-existing metabolic abnormalities.

Exercise therapy in Japan

The purpose of this report is to outline the exercise therapy of diabetes mellitus that has been administered in Japan during the past 10 years, with special emphasis on the results of studies on metabolic and endocrine effects as well as on practical aspects of exercise therapy. The studies on the response to exercise clarified neuroendocrine mechanisms involved in the regulation of carbohydrate and fat metabolism in exercise and provided a basis for the indication of exercise therapy in view of the pre-existing metabolic abnormalities. Concerning the training effects, changes of insulin sensitivity have been chiefly studied in relation to metabolic improvement by physical training using the insulin clamp method. The improvement of glucose and lipid metabolism obtained during the training program, consisting of fast walking or jogging corresponding to 40–60% of predictive VO 2 max for 30–60 min daily, was suggested to be related to improved insulin sensitivity in patients with NIDDM. Intensive studies have been made on exercise programs, and medical checks and guidelines for exercise prescription have been provided. Aerobic exercises with stretching and low-level callisthenics are recommended, and the usefulness of a multi-stage exercise loading test and the necessity of self-monitoring of blood glucose are stressed for the successful management of exercise therapy.