scholarly journals Association of clozapine-related metabolic disturbances with CYP3A4 expression in patients with schizophrenia

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ádám Menus ◽  
Ádám Kiss ◽  
Katalin Tóth ◽  
Dávid Sirok ◽  
Máté Déri ◽  
...  
Keyword(s):  
Side Effects ◽  
Adverse Effects ◽  
Glucose Level ◽  
Fasting Glucose ◽  
Metabolic Disturbances ◽  
Glucose Levels ◽  
Clozapine Concentration ◽  
Metabolic Side Effects ◽  
Increased Risk ◽  
Cyp3a4 Expression

AbstractClozapine is effective in treatment-resistant schizophrenia; however, adverse effects often result in discontinuation of clozapine therapy. Many of the side-effects are associated with pharmacokinetic variations; therefore, the expression of major clozapine-metabolizing enzymes (CYP1A2, CYP3A4) in patients may predict development of adverse effects. In patients with schizophrenia (N = 96), development of clozapine concentration-dependent metabolic side-effects was found to be associated with pharmacokinetic variability related to CYP3A4 but not to CYP1A2 expression. In low CYP3A4 expressers, significant correlation was detected between fasting glucose level and clozapine concentration; moreover, the incidence of abnormal glucose level was associated with exaggerated clozapine concentrations (> 600 ng/ml). In low CYP3A4 expressers, exaggerated concentrations were more frequently observed than in normal/high expressers. Moderate/high risk obesity (BMI ≥ 35) more frequently occurred in low CYP3A4 expresser patients than in normal/high expressers. In patients with normal/high CYP3A4 expression and consequently with extensive clozapine-metabolizing capacity, norclozapine/clozapine ratio correlated with fasting glucose levels, triglyceride concentrations and BMI. Low CYP3A4 expression often resulting in exaggerated clozapine concentrations was considered to be as an important risk factor for some concentration-dependent adverse effects as normal/high CYP3A4 expression evoking high norclozapine/clozapine ratios. CYP3A4-status can identify patients with increased risk for metabolic side-effects and prevent their development by careful therapeutic strategy.

Abstract MP50: Serum Metabolomic Profile of Incident Diabetes

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Casey M Rebholz ◽  
Bing Yu ◽  
Zihe Zheng ◽  
Patrick Chang ◽  
Adrienne Tin ◽  
...  
Keyword(s):  
Fasting Glucose ◽  
Ultra Performance Liquid Chromatography ◽  
Diabetes Risk ◽  
Incident Diabetes ◽  
P Value ◽  
Metabolic Disturbances ◽  
Isoleucine Leucine ◽  
Metabolomics Data ◽  
Metabolomic Profiling ◽  
Increased Risk

Background: Metabolomic profiling offers the potential to reveal metabolic pathways relevant to diabetes pathophysiology and to improve diabetes risk prediction. Methods: We prospectively analyzed metabolites and incident diabetes from baseline (1987-1989) through December 31, 2015 in a subset of 2,939 Atherosclerosis Risk in Communities (ARIC) Study participants with metabolomics data and without diabetes at baseline. Metabolomic profiling was conducted in stored serum specimens collected at baseline using a reverse phase, untargeted ultra-performance liquid chromatography tandem mass spectrometry approach. Results: Among the 245 named compounds we identified, 7 metabolites were significantly associated with incident diabetes after Bonferroni correction and covariate adjustment (age, sex, race, center, batch, education, blood pressures, body mass index, lipids, smoking, physical activity, history of cardiovascular disease, eGFR, fasting glucose). These 7 metabolites consisted of a xenobiotic (erythritol) and compounds involved in amino acid metabolism [isoleucine, leucine, valine, asparagine, 3-(4-hydoxyphenyl)lactate] and glucose metabolism (trehalose). Higher levels of the metabolites were associated with an increased risk of incident diabetes, with the exception of asparagine which was associated with a lower risk of diabetes (HR per 1 SD increase: 0.78, 95% CI: 0.71, 0.85; p=4.19x10 -8 ). The 7 metabolites improved the prediction of incident diabetes beyond fasting glucose and established risk factors (C statistic for model with vs. without 7 metabolites, respectively: 0.744 vs. 0.735; p-value for difference in C statistics=0.001). Conclusions: Branched chain amino acids may play a role in diabetes development. Our study is the first to report asparagine as a protective biomarker of diabetes risk. The serum metabolome reflects known and novel metabolic disturbances that improve diabetes prediction.

scholarly journals POLYCYSTIC OVARIAN SYNDROME;

2012 ◽  
Vol 19 (06) ◽  
pp. 786-788
Author(s):  
KIRAN BUTT ◽  
FARAH DEEBA ◽  
HAVAIDA ATTIQUE
Keyword(s):  
Blood Glucose ◽  
Lipid Profile ◽  
Glucose Level ◽  
Fasting Blood Glucose ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Increased Risk ◽  
Commercial Kits ◽  
The University ◽  
Ovarian Syndrome

Objective: The objective of the present study was to determine the changes in the glucose level and lipid profile in patients withpolycystic ovarian syndrome (PCOS). Study Design: Descriptive study. Place and Duration of the study: This study was conducted atInstitute of Molecular Biology and Biotechnology, The University of Lahore from June 2009 to June 2010. Patients and Methods: Total 50patients with PCOS were included and 50 age-matched control subjects were also selected for comparison. Their glucose levels and lipidprofile were assessed using commercial kits. The data thus obtained was subjected to statistical analysis. Results: Significant differences(P<0.05) in fasting blood glucose level and individual parameters of lipid profile were observed in women with PCOS. A higher prevalence ofhypertriglyceridemia, hypercholesterolemia, higher LDL, lower HDL and higher fasting blood glucose levels was explored in PCOS womenthan controls. Conclusions: Abnormal glucose level and lipid profile in PCOS women showed that these women are at an increased risk ofdeveloping diabetes and subsequently cardiovascular diseases.

scholarly journals The Incremental Risk of Pancreatic Cancer According to Fasting Glucose Levels: Nationwide Population-Based Cohort Study

2019 ◽  
Vol 104 (10) ◽  
pp. 4594-4599 ◽  
Author(s):  
Dong-Hoe Koo ◽  
Kyung-Do Han ◽  
Cheol-Young Park
Keyword(s):  
Pancreatic Cancer ◽  
Glucose Level ◽  
Cumulative Incidence ◽  
Fasting Glucose ◽  
Population Based ◽  
Incidence Rates ◽  
Fasting Glucose Level ◽  
Glucose Levels ◽  
Level 1 ◽  
Level 2

Abstract Context It has been unclear whether the risk of pancreatic cancer is different according to glucose levels. Objective To determine the association between fasting glucose levels and pancreatic cancer risk using prospectively collected nationwide population-based cohort data in Korea. Design The National Health Insurance Service database of claims and preventive health check-up data recorded was used between 2009 and 2015. Setting and Participants A total of 25.4 million patients who had participated in a preventive health check-up between 2009 and 2013 were evaluated for pancreatic cancer incidence rates according to fasting glucose level. Main Outcomes Measures The cumulative incidence rate for pancreatic cancer was calculated after grouping according to fasting glucose levels as follows: (i) low normal (<90 mg/dL), (ii) high normal (90 to 99 mg/dL), (iii) prediabetes level 1 (100 to 109 mg/dL), (iv) prediabetes level 2 (110 to 125 mg/dL), (v) diabetes (≥126 mg/dL), and (vi) diabetes on anti-diabetic medications. Results The 5-year cumulative incidence rates (per 100,000) were as follows: (i) low normal = 32; (ii) high normal = 41; (iii) prediabetes level 1 = 50; (iv) prediabetes level 2 = 64; (v) diabetes = 75; and (vi) on anti-diabetic medications = 121. The risk of pancreatic cancer increased continuously with elevating fasting glucose levels (P < 0.0001). The incidence of pancreatic cancer increased significantly with increasing fasting blood glucose levels even after adjusting for age, sex, smoking, drinking, exercise, body mass index, and diabetes duration (P < 0.0001). Conclusions The cumulative incidence rate of pancreatic cancer significantly increased as the fasting glucose level elevated, even in populations with a normal glucose level range.

scholarly journals Psychotropic drug-induced genetic-epigenetic modulation of CRTC1 gene is associated with early weight gain in a prospective study of psychiatric patients

2019 ◽  
Vol 11 (1) ◽  
Author(s):  
Aurélie Delacrétaz ◽  
Anaïs Glatard ◽  
Céline Dubath ◽  
Mehdi Gholam-Rezaee ◽  
Jose Vicente Sanchez-Mut ◽  
...  
Keyword(s):  
Weight Gain ◽  
Side Effects ◽  
Prospective Study ◽  
Psychotropic Drugs ◽  
Energy Homeostasis ◽  
Psychiatric Patients ◽  
Metabolic Disturbances ◽  
Drug Induced ◽  
Metabolic Side Effects ◽  
Early Weight Gain

Abstract Background Metabolic side effects induced by psychotropic drugs represent a major health issue in psychiatry. CREB-regulated transcription coactivator 1 (CRTC1) gene plays a major role in the regulation of energy homeostasis and epigenetic mechanisms may explain its association with obesity features previously described in psychiatric patients. This prospective study included 78 patients receiving psychotropic drugs that induce metabolic disturbances, with weight and other metabolic parameters monitored regularly. Methylation levels in 76 CRTC1 probes were assessed before and after 1 month of psychotropic treatment in blood samples. Results Significant methylation changes were observed in three CRTC1 CpG sites (i.e., cg07015183, cg12034943, and cg 17006757) in patients with early and important weight gain (i.e., equal or higher than 5% after 1 month; FDR p value = 0.02). Multivariable models showed that methylation decrease in cg12034943 was more important in patients with early weight gain (≥ 5%) than in those who did not gain weight (p = 0.01). Further analyses combining genetic and methylation data showed that cg12034943 was significantly associated with early weight gain in patients carrying the G allele of rs4808844A>G (p = 0.03), a SNP associated with this methylation site (p = 0.03). Conclusions These findings give new insights on psychotropic-induced weight gain and underline the need of future larger prospective epigenetic studies to better understand the complex pathways involved in psychotropic-induced metabolic side effects.

scholarly journals Fatty Acid Desaturase Gene Polymorphisms and Metabolic Measures in Schizophrenia and Bipolar Patients Taking Antipsychotics

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Kyle J. Burghardt ◽  
Kristen N. Gardner ◽  
Joshua W. Johnson ◽  
Vicki L. Ellingrod
Keyword(s):  
Insulin Resistance ◽  
Bipolar Disorder ◽  
Fatty Acid ◽  
Side Effects ◽  
High Risk ◽  
Atypical Antipsychotics ◽  
Fatty Acid Desaturase ◽  
Metabolic Side Effects ◽  
Increased Risk ◽  
Bipolar Patients

Atypical antipsychotics have become a common therapeutic option in both schizophrenia and bipolar disorder. However, these medications come with a high risk of metabolic side effects, particularly dyslipidemia and insulin resistance. Therefore, identification of patients who are at increased risk for metabolic side effects is of great importance. The genetics of fatty acid metabolism is one area of research that may help identify such patients. Therefore, in this present study, we aimed to determine the effect of one commonly studied genetic polymorphism from both fatty acid desaturase 1 (FADS1) and FADS2 gene on a surrogate measure of insulin resistance and lipid levels in a metabolically high-risk population of patients largely exposed to atypical antipsychotics. This study used a cross-sectional design, fasting blood draws, and genetic analysis to investigate associations between polymorphisms, haplotypes, and metabolic measures. A total of 320 subjects with schizophrenia (n=226) or bipolar disorder (n=94) were included in this study. The mean age of the population was 42.5 years and 45% were male. A significant association between FADS1 and FADS2 haplotypes was found with insulin resistance while controlling for confounders. Further investigation is required to replicate this finding.

scholarly journals Influence ofHelicobacter pyloriInfection on Metabolic Syndrome in Old Chinese People

2016 ◽  
Vol 2016 ◽  
pp. 1-4 ◽  
Author(s):  
Wen Yang ◽  
Cunfu Xuan
Keyword(s):  
Metabolic Syndrome ◽  
Fasting Glucose ◽  
Binary Logistic Regression Analysis ◽  
Rapid Urease Test ◽  
Chinese People ◽  
Old Chinese ◽  
Glucose Levels ◽  
Increased Risk ◽  
Urease Test ◽  
H Pylori

Background. H. pyloriinfection is one of the most common chronic infectious inflammatory diseases worldwide and is also a risk factor for atherosclerosis. Patients with metabolic syndrome are known to be at increased risk for atherosclerosis. The aim of our study was to assess the effects ofH. pyloriinfection on serum lipids, body mass index (BMI), and metabolic syndrome in old Chinese people.Material and Method.A total of 191 (133 males and 58 females, aged73.19±11.03years) people who had gastroscopy examination in our hospital were divided intoH. pylori-positive group (n=80) andH. pylori-negative group (n=111).H. pyloriinfection was diagnosed by rapid urease test.Results.Patients withH. pyloriinfection had higher BMI and fasting glucose levels and incidence of metabolic syndrome (p<0.01). It was found that BMI (p<0.01, OR 74.469),H. pyloriinfection (p<0.01, OR 5.427), total cholesterol (p<0.01, OR 15.544), and diabetes mellitus (p<0.01, OR 23.957) were significantly associated with the risk of metabolic syndrome by binary logistic regression analysis.Conclusions.Patients withH. pyloriinfection had higher BMI and fasting glucose levels and had incidence of metabolic syndrome.

scholarly journals Increased Postoperative Fasting Glucose Is Associated With Unfavorable Outcomes in Patients Treated With Mechanical Thrombectomy Treatment

2021 ◽  
Vol 12 ◽  
Author(s):  
Zongjie Shi ◽  
Shunyuan Guo ◽  
Jie Pan ◽  
Chao Xu ◽  
Yu Geng ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Primary Outcome ◽  
Mechanical Thrombectomy ◽  
Fasting Glucose ◽  
Independent Predictor ◽  
Secondary Outcome ◽  
Vessel Occlusion ◽  
Glucose Levels ◽  
Increased Risk ◽  
Symptomatic Intracranial Hemorrhage

Background and objective: Hyperglycemia on admission was associated with worse clinical outcomes after mechanical thrombectomy (MT) of acute ischemic stroke (AIS). We evaluated whether increased postoperative fasting glucose (PFG) was also related to poor clinical outcomes in patients who underwent MT treatment.Methods: Consecutive patients with large vessel occlusion underwent MT in our center were included. Admission glucose and fasting glucose levels after MT treatment were evaluated. Primary outcome was 90-day unfavorable outcomes (modified Rankin Scale score of 3–6). Secondary outcome was the rate of symptomatic intracranial hemorrhage (sICH) after MT treatment. The association of PFG and 90-day clinical outcome after MT treatment was determined using logistic regression analyses.Results: One hundred twenty seven patients were collected. The median postoperative fasting glucose level was 6.27 mmol/L (IQR 5.59–7.62). Fourteen patients (11.02%) had sICH, and fifty-eight patients (45.67%) had unfavorable outcomes at 90-day after MT. After adjustment for potential confounding factors, PFG level was an independent predictor of 90-day unfavorable outcome (OR 1.265; 95% CI 1.017–1.575; p = 0.035) and sICH (OR 1.523; 95% CI 1.056–2.195; p = 0.024) after MT. In addition, older age, higher baseline NIHSS score, and higher postoperative NLR were also associated with unfavorable outcomes at 90-day after MT treatment.Conclusions: Increased PFG is associated with unfavorable outcomes at 90-day and an increased risk of sICH in patients underwent MT treatment.

209Glucose is associated with future atrial fibrillation and heart failure already at prediabetes levels, a 19 year follow up of 243,665 subjects

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
V Lind ◽  
N Hammar ◽  
P Lundman ◽  
L Friberg ◽  
M Tallback ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Glucose Level ◽  
Life Style ◽  
Fasting Glucose ◽  
Diabetes Diagnosis ◽  
Glucose Levels ◽  
The Metabolic Syndrome ◽  
Life Style Changes

Abstract Background Dysglycaemia is associated with cardiovascular disease even below the diagnostic diabetes threshold. Atrial fibrillation (AF) has been found to be associated with the metabolic syndrome and life-style changes after AF have been found to reduce recurrence of AF. Purpose We explored the association glucose and risk of first event of AF, HF and combined event. Methods Subject with fasting glucose in the AMORIS cohort, obtained 1985–1996 at routine occupational health check-ups or primary care in the Stockholm area were included. Subjects with prevalent AF, HF, ischemic heart disease, revascularization and cerebrovascular disease were excluded. Glucose levels were categorised as low (<3.9 mmol/L), normal (3.9–6.0mmol/L), impaired (IFG; 6.1–6.9 mmol/L) and diabetes (≥7.0 mmol/L or a diabetes diagnosis) according to WHO definition in 2006. First events of AF, HF or a combined event was identified until December 2011 by linkage to national registries. Information on co-morbidities was obtained from the National Patient Register. Hazard ratios (HR and 95% CI) by glucose group for AF and heart failure were calculated using Cox proportional hazards with attained age as timescale and adjusting for gender, total cholesterol and triglycerides. The change in AF risk by increasing glucose level was described by using splines (Figure). Results 243 665 subjects with mean age 48.3 at index date, 54% male were included. During a mean follow-up time of 19.1 years and 4,7 million person years, 23 522 events of AF, 21 411 events of HF and 35 131 combined events occurred. The proportion with IFG and diabetes were 3.2% and 3.3% respectively. In the diabetes group about half were diagnosed prevalent cases (1.5%). Glucose was continuously associated with developement of AF (Table and Figure) and even more of HF (Table). Events (n) and HR by glucose category Atrial fibrillation Heart failure Combined event Event HR [95% CI] Event HR [95% CI] Event HR [95% CI] Low 405 0.97 [0.88–1.08] 326 0.97 [0.87–1.08] 598 1.00 [0.92–1.09] Normal 20 663 1.00 17 811 1.00 30 159 1.00 IFG 1185 1.20 [1.13–1.28] 1319 1.43 [1.35–1.51] 1901 1.30 [1.24–1.36] Diabetes 1269 1.28 [1.20–1.35] 1955 2.19 [2.08–2.29] 2473 1.73 [1.66–1.81] Events (n) of AF, HF and combined and HR (95% CI) by fasting glucose category. HR for AF by glucose level spline graph Conclusion Dysglycaemia, including glucose levels below the diabetes threshold, is continuously associated with future risk of both AF and HF. These data are important considering the large population with undetected dysglycaemia at risk for AF and HF where preventive measures including life-style changes could be of importance even before the onset of overt diabetes. Acknowledgement/Funding Swedish Heart and Lung foundation

scholarly journals Colonic inflammation induces changes in glucose levels through modulation of incretin system

2021 ◽  
Author(s):  
Hubert Zatorski ◽  
Maciej Salaga ◽  
Marta Zielińska ◽  
Anna Mokrowiecka ◽  
Damian Jacenik ◽  
...  
Keyword(s):  
Glucose Level ◽  
Healthy Subjects ◽  
Fasting Glucose ◽  
Control Group ◽  
Trinitrobenzenesulfonic Acid ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Dpp Iv ◽  
Prohormone Convertase 1

Abstract Background The role of the incretin hormone, glucagon-like peptide (GLP-1), in Crohn’s disease (CD), is still poorly understood. The aim of this study was to investigate whether colitis is associated with changes in blood glucose levels and the possible involvement of the incretin system as an underlaying factor. Methods We used a murine model of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS). Macroscopic and microscopic score and expression of inflammatory cytokines were measured. The effect of colitis on glucose level was studied by measurement of fasting glucose and GLP-1, dipeptidyl peptidase IV (DPP IV) levels, prohormone convertase 1/3 (PC 1/3) and GLP-1 receptor (GLP-1R) expression in mice. We also measured the level of GLP-1, DPP IV and expression of glucagon (GCG) and PC 1/3 mRNA in serum and colon samples from healthy controls and CD patients. Results Fasting glucose levels were increased in animals with colitis compared to controls. GLP-1 was decreased in both serum and colon of mice with colitis in comparison to the control group. DPP IV levels were significantly increased in serum, but not in the colon of mice with colitis as compared to healthy animals. Furthermore, PC 1/3 and GLP-1R expression levels were increased in mice with colitis as compared to controls. In humans, no differences were observed in fasting glucose level between healthy subjects and CD patients. GLP-1 levels were significantly decreased in the serum. Interestingly, GLP-1 level was significantly increased in colon samples of CD patients compared to healthy subjects. No significant differences in DPP IV levels in serum and colon samples were observed between groups. Conclusions Changes in the incretin system during colitis seem to contribute to the impaired glucose levels. Differences in incretin levels seem to be modulated by degrading enzyme DPP-IV and PC 1/3. Obtained results suggest that the incretin system may become a novel therapeutic approach in the treatment of CD.

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