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Lurasidone and risk for metabolic syndrome: results from short- and long-term clinical studies in patients with schizophrenia.
Tocco, M, Newcomer, JW, Mao, Y, Pikalov, A, Loebel, A
CNS spectrums. 2020;:1-11
Abstract
OBJECTIVE To assess the effects of treatment with lurasidone on risk for metabolic syndrome (MetS) in patients with schizophrenia. METHODS Rates of metabolic syndrome during treatment with lurasidone (40-160 mg/d) were analyzed using pooled, short-term data from three randomized, double-blind, placebo-controlled studies (vs olanzapine and quetiapine XR); long-term data from two active-comparator-controlled studies (vs risperidone and quetiapine XR); and data from two open-label studies in which patients were switched from olanzapine or risperidone to lurasidone. RESULTS MetS was defined based on the National Cholesterol Education Program criteria. In short-term studies, the odds of meeting criteria for MetS at week 6 LOCF (adjusted for baseline metabolic syndrome status) was similar for the lurasidone and placebo groups (OR = 1.18; [95% CI, 0.81-1.71]; P = .39), but the odds (vs placebo) were significantly greater for olanzapine (OR = 2.81; [95% CI, 1.53-5.15]; P < .001) and quetiapine (OR = 3.49; [95% CI, 1.93-6.29]; P < .0001). No dose effect was observed for lurasidone across the dose range of 40-160 mg/d. In long-term studies, the odds of MetS after 12 months of treatment was significantly higher for risperidone compared with lurasidone (OR = 2.12; 95% CI, 1.15-3.90; P = .016) and for quetiapine XR compared with lurasidone (OR = 3.92; 95% CI, 1.15-13.40; P = .029). In open-label extension studies, the rate of MetS decreased in patients switched to lurasidone after 6 weeks of treatment with olanzapine or 12 months of treatment with risperidone. CONCLUSION In this analysis of lurasidone clinical trials, the odds of developing metabolic syndrome were minimal during short- and long-term treatment with lurasidone (40-160 mg/d).
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Effects of Montmorency Tart Cherry Juice Consumption on Cardiometabolic Biomarkers in Adults with Metabolic Syndrome: A Randomized Controlled Pilot Trial.
Johnson, SA, Navaei, N, Pourafshar, S, Jaime, SJ, Akhavan, NS, Alvarez-Alvarado, S, Proaño, GV, Litwin, NS, Clark, EA, Foley, EM, et al
Journal of medicinal food. 2020;(12):1238-1247
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Abstract
Greater than one-third of adults in the United States have metabolic syndrome (MetS), a cluster of risk factors highly associated with the development of cardiovascular diseases. Premature vascular dysfunction in MetS may lead to accelerated age-related atherogenesis and arterial stiffening, thereby increasing cardiovascular risk. Montmorency tart cherries (Prunus cerasus L.) are rich in bioactive compounds, such as anthocyanins, known to exert cardiovascular protective effects. Previous research suggests that tart cherry juice consumption may improve cardiovascular health. The objective of this study was to evaluate the effects of daily consumption of tart cherry juice on hemodynamics, arterial stiffness, and blood biomarkers of cardiovascular and metabolic health in men and women with MetS. In a randomized, single-blind, placebo-controlled, parallel-arm pilot clinical trial, 19 men and women 20 to 60 years of age with MetS consumed 240 mL of tart cherry juice (Tart Cherry; n = 5 males, 4 females) or an isocaloric placebo-control drink (Control; n = 5 males, 5 females) twice daily for 12 weeks. Arterial stiffness (pulse wave velocity), brachial and aortic blood pressures, wave reflection (augmentation index), and blood biomarkers of cardiovascular and metabolic health were assessed at baseline and 6 and 12 weeks. Oxidized low-density lipoprotein and soluble vascular cell adhesion molecule-1 were significantly lower (P = .047 and P = .036, respectively) in Tart Cherry than Control at 12 weeks, but were not significantly lower than baseline values. There was a trend for total cholesterol to be lower (P = .08) in Tart Cherry than Control at 12 weeks. No significant changes were observed in hemodynamics, arterial stiffness, or other blood biomarkers assessed. These results suggest that daily tart cherry consumption may attenuate processes involved in accelerated atherogenesis without affecting hemodynamics or arterial stiffness parameters in this population. The pilot nature of this study warrants interpreting these findings with caution, and future clinical trials with a larger sample size are needed to confirm these findings.
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Diet Quality, Saturated Fat and Metabolic Syndrome.
Harrison, S, Couture, P, Lamarche, B
Nutrients. 2020;(11)
Abstract
Indices reflecting overall diet quality are used globally in research to predict the risk of various diseases and metabolic disorders such as metabolic syndrome (MetS). Such indices are built to measure adherence to current dietary guidelines or to best assess the diet-disease relationship. Although mostly food-based, dietary guidelines often include recommendations to limit saturated fatty acid (SFA) intake in order to prevent cardiovascular diseases. However, not all diet quality indices consider SFA in their definition of diet quality. Additionally, the relationship between SFA consumption and the development of MetS remains unclear. The purpose of this short review was to explore the association between MetS and various diet quality indices and dietary patterns, with a focus on how SFA contributes to these associations.
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Trafficking of nonesterified fatty acids in insulin resistance and relationship to dysglycemia.
Walker, RE, Ford, JL, Boston, RC, Savinova, OV, Harris, WS, Green, MH, Shearer, GC
American journal of physiology. Endocrinology and metabolism. 2020;(3):E392-E404
Abstract
In adipose, insulin functions to suppress intracellular lipolysis and secretion of nonesterified fatty acid (NEFA) into plasma. We applied glucose and NEFA minimal models (MM) following a frequently sampled intravenous glucose tolerance test (FSIVGTT) to assess glucose-specific and NEFA-specific insulin resistance. We used total NEFA and individual fatty acids in the NEFA MM, comparing the model parameters in metabolic syndrome (MetSyn) subjects (n = 52) with optimally healthy controls (OptHC; n = 14). Results are reported as mean difference (95% confidence interval). Using the glucose MM, MetSyn subjects had lower [-73% (-82, -57)] sensitivity to insulin (Si) and higher [138% (44, 293)] acute insulin response to glucose (AIRg). Using the NEFA MM, MetSyn subjects had lower [-24% (-35, -13)] percent suppression, higher [32% (15, 52)] threshold glucose (gs), and a higher [81% (12, 192)] affinity constant altering NEFA secretion (ϕ). Comparing fatty acids, percent suppression was lower in myristic acid (MA) than in all other fatty acids, and the stearic acid (SA) response was so unique that it did not fit the NEFA MM. MA and SA percent of total were increased at 50 min after glucose injection, whereas oleic acid (OA) and palmitic acid (PA) were decreased (P < 0.05). We conclude that the NEFA MM, as well as the response of individual NEFA fatty acids after a FSIVGTT, differ between OptHC and MetSyn subjects and that the NEFA MM parameters differ between individual fatty acids.
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Diabetes management and specific considerations for patients with diabetes during coronavirus diseases pandemic: A scoping review.
Wicaksana, AL, Hertanti, NS, Ferdiana, A, Pramono, RB
Diabetes & metabolic syndrome. 2020;(5):1109-1120
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BACKGROUND AND AIMS The global pandemic of coronavirus (COVID-19) affects almost all countries in the world, which potentially alter diabetes management. Many diabetes patients are experiencing barrier of care due to the policy related to COVID-19. This article aims to review the current evidence on diabetes management and specific considerations during the COVID-19 pandemic for people living with diabetes. METHODS We conducted a scoping review in PubMed, Science Direct, DOAJ and Microsoft Academics databases from January 1 to April 17, 2020. Searching terms included "COVID-19", "severe acute respiratory syndrome coronavirus 2", and "Diabetes Mellitus" were used. Only scientific articles discussing diabetes management and specific considerations were selected and extracted. RESULTS A total of 7 articles was selected in the analysis. Most were published in diabetes journals (85.71%). All articles (100%) discussed diabetes management and 71.43% of them provided diabetes care in specific considerations. We discussed issue of diabetes management in glycemic control and monitoring, dietary intake, physical activity, medication, education and prevention of COVID-19 infection that applicable for diabetes patients. In addition, specific considerations explored caring for diabetes in children and adolescents, pregnancy, elderly, emergency or critical care, to offer certain concern for raising the awareness. CONCLUSIONS This review specifies a summary of diabetes management as well as the particular considerations to care people living with diabetes during COVID-19 pandemic. Patients, health care providers, and policy makers could take advantage of the review to assist diabetic people passing through COVID-19 pandemic session with optimum glycemic outcome.
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Molecular mechanisms of liver damage during neoadjuvant treatment for hepatic metastases of colorectal cancer.
Gmijovic, M, Pecic, V, Stojanovic, M
Annali italiani di chirurgia. 2020;:291-297
Abstract
BACKGROUND The main drawbacks of neoadjuvant chemotherapy of colorectal liver cancer metastases are related to the toxic liver damage. To determine the degree of biochemical and morphologic liver damage after therapeutic protocol treatment with "bevacizumab plus FOLFOX IV", as well as the correlation between the sex, age, the existence of metabolic syndrome, the length of neoadjuvant therapy treatment and the degree of liver damage. METHODS The study includes the total of 60 colorectal cancer metastases operated patients, divided into two groups of 30 patients: the group of patients who were treated with "bevacizumab plus FOLFOX IV" protocol as a neoadjuvant therapy - prior to liver metastases surgery and the control group, patients with the liver resection done without previous neoadjuvant chemotherapy. The following parameters were examined: biochemical liver function parameters, the presence of metabolic syndrome, pathohistological assessment of the degree of steatosis and SOS syndrome. RESULTS The increase in AF was observed in the experimental group (Z = 2.566, p = 0.010), Dbilirubin (Z = 1.970, p = 0.037), LDH (Z = 2.951, p = 0.003) and decrease in albumin values (t = 5.100, p <0.001). The pathohistological examination in only 3.3% showed moderate liver steatosis, while SOS syndrome was recorded in as many as two-thirds (66.66%) of patients in the study group. In 14 patients (46.7%) a mild degree was registered, and in 6 (20.0%) moderate levels of this type of liver damage. Pole (p = 0.13), age (p = 0.09) and length of administration of chemotherapy (p = 0.35), as well as the presence of metabolic syndrome (χ2 = 0.390, p = 0.830), did not have any statistically significant effect on the liver damage degree. CONCLUSION In our study, after the administration of the "bevacizumab plus FOLFOX IV" protocol, a statistically significant increase in AF, Dbilirubin and LDH, as well as a decrease in albumin values, were found. Dominant liver damage was by type of SOS syndrome (66.7%), while steatosis of the liver was recorded in only 3.3% of patients. Gender, age, the presence of metabolic syndrome and the number of chemotherapy cycles did not have any statistic significance on the biochemical parameters and morphological degree of liver damage. KEY WORDS Colorectal cancer metastases, Liver surgery, Oncology, Neoadjuvant chemotherapy, Liver damage.
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Extraglycemic Effects of SGLT2 Inhibitors: A Review of the Evidence.
Bonora, BM, Avogaro, A, Fadini, GP
Diabetes, metabolic syndrome and obesity : targets and therapy. 2020;:161-174
Abstract
Patients with type 2 diabetes (T2D) are often overweight/obese and affected by arterial hypertension, dyslipidaemia, and have high serum levels of uric acid. Moreover, T2D patient have a higher risk of developing cardiovascular or renal complications, which are leading causes of morbidity and mortality in this population. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a new class of glucose-lowering medications that block the reabsorption of glucose in the kidney, thereby increasing urinary glucose excretion, and lowering blood glucose levels. The beneficial effects of SGLT2 inhibition extend beyond glycaemic control, and include improvement in blood pressure, body weight, uric acid concentrations, liver steatosis, oxidative stress, and inflammation. In dedicated cardiovascular outcome trials, SGLT2i treatment was associated with a significant reduction in the rate of cardiovascular events and renal endpoints. In this review, we summarize the evidence for extra-glycemic effects of SGLT2i and the potential mechanisms driving cardiorenal protection exerted by this class of medications.
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Clinical Efficacy and Transcriptomic Analysis of Congrong Shujing Granules () in Patients with Parkinson's Disease and Syndrome of Shen (Kidney) Essence Deficiency.
Chen, SY, Xiao, SJ, Lin, YN, Li, XY, Xu, Q, Yang, SS, Huang, LH, Cai, J
Chinese journal of integrative medicine. 2020;(6):412-419
Abstract
OBJECTIVE To evaluate the clinical efficacy and safety of Congrong Shujing Granules ( , CSGs) in treating patients with Parkinson's disease (PD) and Chinese medicine (CM) syndrome of Shen (Kidney) essence deficiency, and to investigate the potential mechanism involving efficacy through a transcriptome sequencing approach. METHODS Eligible PD patients with syndrome of Shen essence defificiency were randomly assigned to a treatment group or a control group by a random number table, and were treated with CSGs combined with Western medicine (WM), or placebo combined with WM, respectively. Both courses of treatment lasted for 12 weeks. The Unifified Parkinson's Disease Rating Scale (UPDRS) score, the PD Question-39 (PDQ-39) score, CM Syndrome Scale score, and drug usage of all patients were evaluated before and after treatment. Safety was evaluated by clinical laboratory tests and electrocardiographs. Blood samples from 6 patients in each group were collected before and after the trial and used for transcriptomic analysis by gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis. Differentially expressed genes were validated using reverse transcription-polymerase chain reaction. RESULTS A total of 86 PD patients were selected from the Third Affifiliated People's Hospital of Fujian University of Traditional Chinese Medicine between January 2017 and December 2017. Finally, 72 patients completed the trial, including 35 in the treatment group and 37 in the control group. When compared with the control group after treatment, patients in the treatment group showed signifificant decreases in UPDRS sub-II score, PDQ-39 score, CM syndrome score, and Levodopa equivalent dose (P<0.05). During the treatment course, no signifificant changes were observed in safety indicators between the two groups (P>0.05). A possible mechanism of clinical effificacy was proposed that involved regulating cell metabolism-related processes and ribosome-related pathways. Treatment with CSGs had shown to affect relevant gene loci for PD, including AIDA, ANKRD36BP2, BCL2A1, BCL2L11, FTH1P2, GCH1, HPRT1, NFE2L2, RMRP, RPS7, TGFBR1, WIPF2, and COX7B. CONCLUSIONS CSGs combined with WM can be used to treat PD patients with CM syndrome of Shen essence defificiency with a good safety. The possible mechanism of action and relevant gene loci were proposed. (Registration No. ChiCTR-IOR-16008394).
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Serum Metabolomic Profiles Associated With Untreated Metabolic Syndrome Patients in the Chinese Population.
Li, Y, Wang, Y, Zhuang, Y, Zhang, P, Chen, S, Asakawa, T, Gao, B
Clinical and translational science. 2020;(6):1271-1278
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Abstract
Metabolomics is a promising technology for elucidating the mechanisms of metabolic syndrome (MetS). However, measurements in patients with MetS under different conditions vary. Metabolomics experiments in different populations and pathophysiological conditions are, therefore, indispensable. We performed a serum metabolomics investigation in untreated patients with MetS in the Chinese population. Untreated patients with MetS were recruited to this study. Metabolites were measured using a traditional 1 H nuclear magnetic resonance (NMR) experiment followed by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Key metabolic pathways were identified by searching the Kyoto Encyclopedia of Genes and Genomes Pathway Database. A total of 28 patients with MetS and 30 healthy subjects were enrolled. All patients were untreated because they were unaware of or neglected to treat their MetS. By 1 H NMR, we identified 49 known substances. Following PCA and OPLS-DA, 36 metabolites were confirmed to be closely associated with MetS compared with the control group; 33 metabolites were increased, whereas 3 metabolites were reduced. Importantly, 14 metabolites that changed in the serum of these untreated patients with MetS were previously unreported. Pathway analysis revealed the top 15 metabolic pathways associated with untreated MetS, which included 3 amino acid metabolic pathways. Our data suggest that untreated patients exhibit a worse pathophysiologic manifestation, which may result in more rapid progression of MetS. Thus, we propose that health education be reinforced to improve the public's knowledge, attitude, and practice regarding MetS. The rates of "untreated" patients due to unawareness and neglect must be reduced immediately.
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Pharmacological Management of Glucose Dysregulation in Patients Treated with Second-Generation Antipsychotics.
Cernea, S, Dima, L, Correll, CU, Manu, P
Drugs. 2020;(17):1763-1781
Abstract
Fasting hyperglycemia, impaired glucose tolerance, prediabetes, and diabetes are frequently present in patients treated with second-generation antipsychotics (SGAPs) for schizophrenia, bipolar disorder, and other severe mental illnesses. These drugs are known to produce weight gain, which may lead to insulin resistance, glucose intolerance, and metabolic syndrome, which constitute important risk factors for the emergence of diabetes. The aim of this review was to formulate therapeutic guidelines for the management of diabetes in patients treated with SGAPs, based on the association between SGAP-induced weight gain and glucose dysregulation. A systematic search in PubMed from inception to March 2020 for randomized controlled trials (RCTs) of diabetes or prediabetes in patients treated with SGAPs was performed. PubMed was also searched for the most recent clinical practice guidelines of interventions for co-morbid conditions associated with diabetes mellitus (DM) (arterial hypertension and dyslipidemia), lifestyle interventions and switching from high metabolic liability SGAPs to safer SGAPs. The search identified 14 RCTs in patients treated with SGAPs. Drug therapy using metformin as first-line therapy and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or perhaps sodium-glucose cotransporter-2 (SGLT2) inhibitors as add-on therapy, might be preferred in these patients as well, as they favorably influence glucose metabolism and body mass index, and provide cardio-renal benefits in general to the DM population, although for the SGLT-2 inhibitors there are no RCTs in this specific patient category so far. Metformin is also useful for treatment of prediabetes. Arterial hypertension should be treated with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, and statins should be used for correction of dyslipidemia. The outcome of lifestyle-changing interventions has been disappointing. Switching from clozapine, olanzapine, or quetiapine to lower cardiometabolic-risk SGAPs, like aripiprazole, brexpiprazole, cariprazine, lurasidone, or ziprasidone, has been recommended.