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Adiposity and Cardiometabolic Risk in Children With and Without Antipsychotic Drug Treatment.

ABSTRACT: Pediatric obesity is common, particularly in children treated with antipsychotic medications. Antipsychotic exposure can increase cardiometabolic risk by increasing adiposity, and possibly via other adiposity-independent pathways.The objectives were to characterize relationships of adiposity with intrahepatic triglyceride (IHTG) content and carotid intima media thickness (CIMT) in children with and without antipsychotic drug treatment, and to explore whether vitamin D alters any effects in these relationships.This was a cross-sectional case-control study.The setting was an academic medical center.Participants were 44 children (ages, 6-19 y): 25 cases treated with antipsychotic and other psychotropic drug therapies and 19 untreated controls, frequency-matched on age, gender, and body mass index.Main outcome measures were dual-energy x-ray absorptiometry percentage body fat (DEXA %fat), IHTG measured by magnetic resonance spectroscopy, and CIMT measured by ultrasonography. Fasting blood glucose, insulin, lipids, C-reactive protein, and liver enzymes were also evaluated.There were no significant differences between cases and controls on measures of IHTG, CIMT, or DEXA %fat. In combined crude and adjusted analyses, DEXA %fat predicted IHTG (R(2) = 0.30) but not CIMT. Low levels of vitamin D were associated with larger effects of DEXA %fat on IHTG.In treated and untreated children alike, adiposity is a significant predictor of liver fat content. This relationship was altered by low vitamin D level. These results suggest a modifiable pathway to hepatic steatosis. Further research is needed to test the hypothesis that children with high adiposity and low vitamin D have particularly increased risks for the development of fatty liver.

SUBMITTER: Nicol GE

PROVIDER: S-EPMC4570158 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Adiposity and Cardiometabolic Risk in Children With and Without Antipsychotic Drug Treatment.

Nicol Ginger E GE de Las Fuentes Lisa L Riek Amy E AE Bernal-Mizrachi Carlos C Lenze Eric J EJ Miller J Phillip JP Schweiger Julia A JA Yingling Michael D MD Huang Vincent J VJ Dixon David J DJ Hennekens Charles H CH Newcomer John W JW

The Journal of clinical endocrinology and metabolism 20150717 9

<h4>Context</h4>Pediatric obesity is common, particularly in children treated with antipsychotic medications. Antipsychotic exposure can increase cardiometabolic risk by increasing adiposity, and possibly via other adiposity-independent pathways.<h4>Objective</h4>The objectives were to characterize relationships of adiposity with intrahepatic triglyceride (IHTG) content and carotid intima media thickness (CIMT) in children with and without antipsychotic drug treatment, and to explore whether vit ...[more]

PMID: 26186300

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Project description:BackgroundIt is largely unknown how TV use relates to depot-specific adiposity or cardiometabolic risk in children.PurposeTo examine relationships between having a TV in the bedroom and TV viewing time with total fat mass, abdominal subcutaneous and visceral adiposity, and cardiometabolic risk in children and adolescents.MethodsA cross-sectional study of 369 children and adolescents aged 5-18 years was conducted (2010-2011; analysis 2011-2012). Waist circumference; resting blood pressure; fasting triglycerides, high-density lipoprotein cholesterol [HDL-C] and glucose; fat mass by dual-energy x-ray absorptiometry; and abdominal subcutaneous and visceral adiposity by MRI were assessed. Cardiometabolic risk was defined as three or more risk factors including adverse levels of waist circumference, blood pressure, triglycerides, HDL-C, and glucose. Logistic regression analysis was used to compute ORs of high fat mass; subcutaneous and visceral adipose tissue mass (top age-adjusted quartile); and cardiometabolic risk, based on self-reported TV present in the bedroom and TV viewing time, controlling for age, gender, ethnicity, moderate-to-vigorous physical activity level, and unhealthy diet.ResultsIn multivariable models, presence of a TV in the bedroom and TV viewing time were associated with (p<0.05) higher odds of high waist circumference (OR=1.9-2.1); fat mass (OR=2.0-2.5); and subcutaneous adiposity (OR=2.1-2.9), whereas viewing TV ≥5 hours/day was associated with high visceral adiposity (OR=2.0). Having a TV in the bedroom was associated with elevated cardiometabolic risk (OR=2.9) and high triglycerides (OR=2.0).ConclusionsHaving a bedroom TV and TV viewing time were related to high waist circumference, fat mass, and abdominal subcutaneous adiposity. TV viewing time was related to visceral adiposity, and bedroom TV was related to cardiometabolic risk in children, controlling for moderate-to-vigorous physical activity and an unhealthy diet.RegistrationThis study is registered at Clinicaltrials.govNCT01595100.

Project description:Objective: Adiposity induces the clustering of cardiometabolic risk factors, and pediatric adiposity is a better indicator for adulthood cardiometabolic diseases than pediatric metabolic syndrome. However, the observed prevalence of pediatric adiposity depends on the methods and cut-points used. Therefore, we aimed to define diagnostic criteria for adiposity which enable more valid identification of prepubertal children at increased cardiometabolic risk. Methods: The participants were 470 prepubertal children (249 boys) aged 6-8 years. The measures of adiposity included body mass index-standard deviation score (BMI-SDS), waist-to-height ratio (WHtR) and body fat percentage (BF%) assessed by bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DXA). Criteria for adiposity were determined by increased cardiometabolic risk. Cardiometabolic risk factors which correlated with BF% assessed by DXA in the upper but not lower half of BF% (serum insulin and plasma high-density lipoprotein cholesterol, triglycerides, gamma-glutamyl transferase, high-sensitivity C-reactive protein and uric acid) were included in the cardiometabolic risk score (CMS). We computed receiver operating characteristics curves for the measures of adiposity using the ≥90th percentile of CMS as a measure of increased cardiometabolic risk, and local regression curves were graphed to demonstrate the associations of the measures of adiposity with CMS. Results: In girls, WHtR of 0.445 (area under curve 0.778, its 95% confidence interval 0.65-0.91, sensitivity and specificity 0.73) and BF% of 19.5% assessed by BIA (0.801, 0.70-0.90, 0.73) were the best overall criteria for increased cardiometabolic risk. In boys, BMI-SDS of 0.48 (0.833, 0.75-0.92, 0.76) was the best overall criterion for increased cardiometabolic risk. While local regression curves in girls showed that WHtR of 0.445 corresponds well to a point where CMS began to increase, in boys local regression curves suggest that CMS began to increase even at a lower level of BMI-SDS than 0.48. Moreover, the diagnostic ability of the measures of adiposity to exclude increased cardiometabolic risk was poorer than the ability to detect it. Conclusions: In general, the measures of adiposity have sufficient diagnostic accuracy to be utilized as the screening tool for increased cardiometabolic risk. The observed cut-points for adiposity were lower than the traditional cut-points for adiposity.

Project description:BACKGROUND:Mendelian randomization studies in adults suggest that abdominal adiposity is causally associated with increased risk of type 2 diabetes and coronary artery disease in adults, but its causal effect on cardiometabolic risk in children remains unclear. OBJECTIVE:We aimed to study the causal relation of abdominal adiposity with cardiometabolic risk factors in children by applying Mendelian randomization. METHODS:We constructed a genetic risk score (GRS) using variants previously associated with waist-to-hip ratio adjusted for BMI (WHRadjBMI) and examined its associations with cardiometabolic factors by linear regression and Mendelian randomization in a meta-analysis of 6 cohorts, including 9895 European children and adolescents aged 3-17 y. RESULTS:WHRadjBMI GRS was associated with higher WHRadjBMI (? = 0.021 SD/allele; 95% CI: 0.016, 0.026 SD/allele; P = 3 × 10-15) and with unfavorable concentrations of blood lipids (higher LDL cholesterol: ? = 0.006 SD/allele; 95% CI: 0.001, 0.011 SD/allele; P = 0.025; lower HDL cholesterol: ? = -0.007 SD/allele; 95% CI: -0.012, -0.002 SD/allele; P = 0.009; higher triglycerides: ? = 0.007 SD/allele; 95% CI: 0.002, 0.012 SD/allele; P = 0.006). No differences were detected between prepubertal and pubertal/postpubertal children. The WHRadjBMI GRS had a stronger association with fasting insulin in children and adolescents with overweight/obesity (? = 0.016 SD/allele; 95% CI: 0.001, 0.032 SD/allele; P = 0.037) than in those with normal weight (? = -0.002 SD/allele; 95% CI: -0.010, 0.006 SD/allele; P = 0.605) (P for difference = 0.034). In a 2-stage least-squares regression analysis, each genetically instrumented 1-SD increase in WHRadjBMI increased circulating triglycerides by 0.17 mmol/L (0.35 SD, P = 0.040), suggesting that the relation between abdominal adiposity and circulating triglycerides may be causal. CONCLUSIONS:Abdominal adiposity may have a causal, unfavorable effect on plasma triglycerides and potentially other cardiometabolic risk factors starting in childhood. The results highlight the importance of early weight management through healthy dietary habits and physically active lifestyle among children with a tendency for abdominal adiposity.

Project description:ImportanceChildren and youths who are prescribed antipsychotic medications have multiple, potentially fatal, dose-related cardiovascular, metabolic, and other adverse events, but whether or not these medications are associated with an increased risk of death is unknown.ObjectiveTo compare the risk of unexpected death among children and youths who are beginning treatment with antipsychotic or control medications.Design, setting, and participantsThis retrospective cohort study was conducted from 1999 through 2014 and included Medicaid enrollees aged 5 to 24 years in Tennessee who had no diagnosis of severe somatic illness, schizophrenia or related psychoses, or Tourette syndrome or chronic tic disorder. Data analysis was performed from January 1, 2017, to August 15, 2018.ExposuresCurrent, new antipsychotic medication use at doses higher than 50 mg (higher-dose group) or 50 mg or lower chlorpromazine equivalents (lower-dose group) as well as control medications (ie, attention-deficit/hyperactivity disorder medications, antidepressants, or mood stabilizers) (control group).Main outcomes and measuresDeaths during study follow-up while out of hospital or within 7 days after hospital admission, classified as either deaths due to injury or suicide or unexpected deaths. Secondary outcomes were unexpected deaths not due to overdose and death due to cardiovascular or metabolic causes.ResultsThis study included 189 361 children and youths in the control group (mean [SD] age, 12.0 [5.1] years; 43.4% female), 28 377 in the lower-dose group (mean [SD] age, 11.7 [4.4] years; 32.3% female), and 30 120 in the higher-dose group (mean [SD] age, 14.5 [4.8] years; 39.2% female). The unadjusted incidence of death in the higher-dose group was 146.2 per 100 000 person-years (40 deaths per 27 354 person-years), which was significantly greater than that in the control group (54.5 per 100 000 population; 67 deaths per 123 005 person-years) (P < .001). The difference was primarily attributable to the increased incidence of unexpected deaths in the higher-dose group (21 deaths; 76.8 per 100 000 population) compared with the control group (22 deaths; 17.9 per 100 000 population). The propensity score-adjusted hazard ratios were as follows: all deaths (1.80; 95% CI, 1.06-3.07), deaths due to unintentional injury or suicide (1.03; 95% CI, 0.53-2.01), and unexpected deaths (3.51; 95% CI, 1.54-7.96). The hazard ratio was 3.50 (95% CI, 1.35-9.11) for unexpected deaths not due to overdose and 4.29 (95% CI, 1.33-13.89) for deaths due to cardiovascular or metabolic causes. Neither the unadjusted nor adjusted incidence of death in the lower-dose group differed significantly from that in the control group.Conclusions and relevanceThe findings suggest that antipsychotic use is associated with increased risk of unexpected death and appear to reinforce recommendations for careful prescribing and monitoring of antipsychotic treatment for children and youths and to underscore the need for larger antipsychotic treatment safety studies in this population.

Project description:BackgroundWeight loss and increased physical fitness are established approaches to reduce cardiovascular risk factors. We studied the reduction in BMI z-score associated with improvement in cardiometabolic risk factors in overweight and obese children and adolescents treated with a combined hospital/public health nurse model. We also examined how aerobic fitness influenced the results.MethodsFrom 2004-2007, 307 overweight and obese children and adolescents aged 7-17 years were referred to an outpatient hospital pediatrics clinic and evaluated by a multidisciplinary team. Together with family members, they were counseled regarding diet and physical activity at biannual clinic visits. Visits with the public health nurse at local schools or at maternal and child health centres were scheduled between the hospital consultations. Fasting blood samples were taken at baseline and after one year, and aerobic fitness (VO2peak) was measured. In the analyses, 230 subjects completing one year of follow-up by December 2008 were divided into four groups according to changes in BMI z-score: Group 1: decrease in BMI z-score?0.23, Group 2: decrease in BMI z-score?0.1-< 0.23, Group 3: decrease in/stable BMI z-score?0.0-< 0.1, Group 4: increase in BMI z-score (>0.00-0.55).Results230 participants were included in the analyses (75%). Mean (SD) BMI z-score was reduced from 2.18 (0.30) to 2.05 (0.39) (p < 0.001) in the group as a whole. After adjustment for BMI z-score, waist circumference and gender, the three groups with reduced BMI z-score had a significantly greater reduction in HOMA-IR, insulin, total cholesterol, LDL cholesterol and total/HDL cholesterol ratio than the group with increased BMI z-score. Adding change in aerobic fitness to the model had little influence on the results. Even a very small reduction in BMI z-score (group 3) was associated with significantly lower insulin, total cholesterol, LDL and total/HDL cholesterol ratio. The group with the largest reduction in BMI z-score had improvements in HOMA-IR and aerobic fitness as well. An increase in BMI z-score was associated with worsening of C-peptide and total/HDL cholesterol ratio.ConclusionsEven a modest reduction in BMI z-score after one year of combined hospital/and public health nurse intervention was associated with improvement in several cardiovascular risk factors.

Dataset Information

Adiposity and Cardiometabolic Risk in Children With and Without Antipsychotic Drug Treatment.

Publications

Adiposity and Cardiometabolic Risk in Children With and Without Antipsychotic Drug Treatment.

Similar Datasets

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