Geisinger Obesity Institute

Danville, PA, United States

Geisinger Obesity Institute

Danville, PA, United States
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Ford D.W.,Pennsylvania State University | Hartman T.J.,Emory University | Still C.,Geisinger Obesity Institute | Wood C.,Geisinger Obesity Institute | And 5 more authors.
Journal of Nutrition in Gerontology and Geriatrics | Year: 2014

In an aging population, potentially modifiable factors impacting mortality such as diet quality, body mass index (BMI), and health-related quality of life (HRQOL) are of interest. Surviving members of the Geisinger Rural Aging Study (GRAS) (n = 5,993; aged?74 years) were contacted in the fall of 2009. Participants in the present study were the 2,995 (1,267 male, 1,728 female; mean age 81.4 ± 4.4 years) who completed dietary and demographic questionnaires and were enrolled in the Geisinger Health Plan over follow-up (mean = 3.1 years). Cox proportional hazards multivariate regression models were used to examine the associations between all-cause mortality and BMI, diet quality, and HRQOL. Compared to GRAS participants with BMIs in the normal range, a BMI < 18.5 was associated with increased mortality (HR 1.85 95%CI 1.09, 3.14, P = 0.02), while a BMI of 25-29.9 was associated with decreased risk of mortality (HR 0.71 95%CI 0.55, 0.91, P =0.007). Poor diet quality increased risk for mortality (HR 1.53 95%CI 1.06, 2.22, P = 0.02). Finally, favorable health-related quality of life was inversely associated with mortality (HR 0.09 95%CI 0.06, 0.13, P < 0.0001). Higher diet quality and HALex scores, and overweight status, were associated with reduced all-cause mortality in a cohort of advanced age. While underweight (BMI < 18.5) increased risk of all-cause mortality, no association was found between obesity and all-cause mortality in this aged cohort. © 2014 Taylor & Francis Group, LLC.


Hirsch A.G.,Geisinger Center for Health Research | Wood G.C.,Geisinger Obesity Institute | Wood G.C.,Weis Center for Research | Bailey-Davis L.,Geisinger Center for Health Research | And 4 more authors.
Obesity | Year: 2014

Objective: To evaluate the impact of adult bariatric surgery on the body mass index (BMI) of children living in the same household. Methods: A retrospective case-control study. Case dyads (n = 128) were composed of one adult who had bariatric surgery and one child at the same address. Control dyads (n = 384) were composed of an adult with obesity but no bariatric surgery and a child at the same address. Two-sample t-test was used to determine whether the differences between actual and expected BMI at follow-up (post-surgery) differed between children in the case and control dyads. Results: Among boys who were overweight, boys who lived with a surgery patient had a lower than expected BMI post-surgery, while boys who did not live with a surgery patient had a higher than expected BMI at follow-up (P = 0.045). Differences between actual and expected BMIs of children were not significantly different between cases and controls in girls or in children in other weight classes. Conclusions: Overweight boys who lived with an adult bariatric surgery patient had a lower than expected BMI after surgery as compared to controls. Future studies may be warranted to determine the mechanisms by which these children experience collateral weight loss. © 2014 The Obesity Society.


Benotti P.,Geisinger Obesity Institute | Wood G.C.,Geisinger Obesity Institute | Argyropoulos G.,Geisinger Obesity Institute | Pack A.,University of Pennsylvania | And 4 more authors.
Obesity | Year: 2016

Objective Obstructive sleep apnea (OSA) is common among candidates for bariatric surgery. OSA and its associated intermittent hypoxia have been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis. A large cohort of bariatric surgery patients was studied in an effort to explore the relationship between OSA severity, hypoxia, metabolic syndrome, and the severity of NAFLD. Methods Bariatric surgery candidates who underwent both polysomnography and liver biopsy were studied. The severity of OSA as determined by the apnea-hypopnea index (AHI) and parameters of hypoxia was studied in relation to extent of abnormalities of liver histology as measured by the presence of hepatic steatosis, inflammation, and fibrosis. Results The study cohort included 362 patients with a mean age of 46.2 years and BMI of 49.9 kg/m2. On the basis of AHI, 26% of the cohort had no OSA, 32% mild OSA, 22% moderate OSA, and 20% severe OSA. For the study subjects without metabolic syndrome, positive correlations were found between OSA severity, as measured by AHI, and parameters of hypoxia, with the severity of NAFLD. Conclusions OSA severity and its accompanying hypoxia are associated with the severity of NAFLD. © 2016 The Obesity Society.


PubMed | Pennsylvania State University, University of Pennsylvania, Temple University and Geisinger Obesity Institute
Type: Journal Article | Journal: Obesity (Silver Spring, Md.) | Year: 2016

Obstructive sleep apnea (OSA) is common among candidates for bariatric surgery. OSA and its associated intermittent hypoxia have been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis. A large cohort of bariatric surgery patients was studied in an effort to explore the relationship between OSA severity, hypoxia, metabolic syndrome, and the severity of NAFLD.Bariatric surgery candidates who underwent both polysomnography and liver biopsy were studied. The severity of OSA as determined by the apnea-hypopnea index (AHI) and parameters of hypoxia was studied in relation to extent of abnormalities of liver histology as measured by the presence of hepatic steatosis, inflammation, and fibrosis.The study cohort included 362 patients with a mean age of 46.2 years and BMI of 49.9 kg/m(2) . On the basis of AHI, 26% of the cohort had no OSA, 32% mild OSA, 22% moderate OSA, and 20% severe OSA. For the study subjects without metabolic syndrome, positive correlations were found between OSA severity, as measured by AHI, and parameters of hypoxia, with the severity of NAFLD.OSA severity and its accompanying hypoxia are associated with the severity of NAFLD.


PubMed | Thomas Jefferson University, University of Pennsylvania, Temple University, Yale University and 2 more.
Type: | Journal: Obesity (Silver Spring, Md.) | Year: 2016

To examine neural mechanisms of action in behavioral weight loss treatment (BWL) and explore neural and genetic predictors of BWL.Neural activation to milkshake receipt and genetics were compared in 17 women with obesity who received 12 weeks of BWL and 17 women who received no intervention. Participants were scanned twice using functional magnetic resonance imaging at baseline and 12 weeks. Weight was assessed at baseline, 12, 36, and 60 weeks.BWL participants lost more weight than controls at 12 weeks (-4.82% versus -0.70%). After 12 weeks, BWL had greater reduction in right caudate activation response to milk shake receipt than did controls. Among BWL participants, baseline to 12-week reduction in frontostriatal activation to milk shake predicted greater weight loss at 12, 36, and 60 weeks. Possessing the A/A or T/A genotype of the fat mass and obesity-associated (FTO) variant rs9939609 predicted greater weight loss at 12 and 36 weeks.These preliminary data reveal that reduction in right caudate activation may be a neural mechanism of weight loss in BWL, and baseline FTO variant and reduction in frontostriatal activation during BWL predict short- and long-term weight loss. These findings require replication in larger samples.


Moore B.S.,Weis Center for Research | Mirshahi U.L.,Weis Center for Research | Yost E.A.,Weis Center for Research | Stepanchick A.N.,Weis Center for Research | And 9 more authors.
PLoS ONE | Year: 2014

Background: The melanocortin 4 receptor (MC4R) critically regulates feeding and satiety. Rare variants in MC4R are predominantly found in obese individuals. Though some rare variants in MC4R discovered in patients have defects in localization, ligand binding and signaling to cAMP, many have no recognized defects. Subjects/Methods: In our cohort of 1433 obese subjects that underwent Roux-en-Y Gastric Bypass (RYGB) surgery, we found fifteen variants of MC4R. We matched rare variant carriers to patients with the MC4R reference alleles for gender, age, starting BMI and T2D to determine the variant effect on weight-loss post-RYGB. In vitro, we determined expression of mutant receptors by ELISA and western blot, and cAMP production by microscopy. Results: While carrying a rare MC4R allele is associated with obesity, carriers of rare variants exhibited comparable weight-loss after RYGB to non-carriers. However, subjects carrying three of these variants, V95I, I137T or L250Q, lost less weight after surgery. In vitro, the R305Q mutation caused a defect in cell surface expression while only the I137T and C326R mutations showed impaired cAMP signaling. Despite these apparent differences, there was no correlation between in vitro signaling and pre- or post-surgery clinical phenotype. Conclusions: These data suggest that subtle differences in receptor signaling conferred by rare MC4R variants combined with additional factors predispose carriers to obesity. In the absence of complete MC4R deficiency, these differences can be overcome by the powerful weight-reducing effects of bariatric surgery. In a complex disorder such as obesity, genetic variants that cause subtle defects that have cumulative effects can be overcome after appropriate clinical intervention. © 2014 Moore et al.


Parihar A.,University of Maryland Baltimore County | Wood G.C.,Geisinger Obesity Institute | Chu X.,Geisinger Obesity Institute | Jin Q.,Pennsylvania State University | And 7 more authors.
Frontiers in Genetics | Year: 2014

A variety of health-related data are commonly deposited into electronic health records (EHRs), including laboratory, diagnostic, and medication information. The digital nature of EHR data facilitates efficient extraction of these data for research studies, including genome-wide association studies (GWAS). Previous GWAS have identified numerous SNPs associated with variation in total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG). These findings have led to the development of specialized genotyping platforms that can be used for fine-mapping and replication in other populations. We have combined the efficiency of EHR data and the economic advantages of the Illumina Metabochip, a custom designed SNP chip targeted to traits related to coronary artery disease, myocardial infarction, and type 2 diabetes, to conduct an array-wide analysis of lipid traits in a population with extreme obesity. Our analyses identified associations with 12 of 21 previously identified lipid-associated SNPs with effect sizes similar to prior results. Association analysis using several approaches to account for lipid-lowering medication use resulted in fewer and less strongly associated SNPs. The availability of phenotype data from the EHR and the economic efficiency of the specialized Metabochip can be exploited to conduct multi-faceted genetic association analyses. © 2014 Parihar, Wood, Chu, Jin, Argyropoulos, Still, Shuldiner, Mitchell and Gerhard.


Leti F.,Translational Genomics Research Institute | Malenica I.,Translational Genomics Research Institute | Doshi M.,Translational Genomics Research Institute | Courtright A.,Translational Genomics Research Institute | And 5 more authors.
Translational Research | Year: 2015

Recent evidence suggests that microRNAs (miRNAs), small, noncoding RNA molecules that regulate gene expression, may play a role in the regulation of metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). To identify miRNAs that mediate NAFLD-related fibrosis, we used high-throughput sequencing to assess miRNAs obtained from liver biopsies of 15 individuals without NAFLD fibrosis (F0) and 15 individuals with severe NAFLD fibrosis or cirrhosis (F3-F4), matched for age, sex, body mass index, type 2 diabetes status, hemoglobin A1c, and use of diabetes medications. We used DESeq2 and Kruskal-Wallis test to identify miRNAs that were differentially expressed between NAFLD patients with or without fibrosis, adjusting for multiple testing using Bonferroni correction. We identified a total of 75 miRNAs showing statistically significant evidence (adjusted P value <0.05) for differential expression between the 2 groups, including 30 upregulated and 45 downregulated miRNAs. Quantitative reverse-transcription polymerase chain reaction analysis of selected miRNAs identified by sequencing validated 9 of 11 of the top differentially expressed miRNAs. We performed functional enrichment analysis of dysregulated miRNAs and identified several potential gene targets related to NAFLD-related fibrosis including hepatic fibrosis, hepatic stellate cell activation, transforming growth factor beta signaling, and apoptosis signaling. We identified forkhead box O3 and F-box WD repeat domain containing 7, E3 ubiquitin protein ligase (FBXW7) as potential targets of miR-182, and found that levels of forkhead box O3, but not FBXW7, were significantly decreased in fibrotic samples. These findings support a role for hepatic miRNAs in the pathogenesis of NAFLD-related fibrosis and yield possible new insight into the molecular mechanisms underlying the initiation and progression of liver fibrosis and cirrhosis. © 2015 Elsevier Inc. All rights reserved.


PubMed | Temple University, Geisinger Obesity Institute and Translational Genomics Research Institute
Type: Journal Article | Journal: Translational research : the journal of laboratory and clinical medicine | Year: 2015

Recent evidence suggests that microRNAs (miRNAs), small, noncoding RNA molecules that regulate gene expression, may play a role in the regulation of metabolic disorders, including nonalcoholic fatty liver disease (NAFLD). To identify miRNAs that mediate NAFLD-related fibrosis, we used high-throughput sequencing to assess miRNAs obtained from liver biopsies of 15 individuals without NAFLD fibrosis (F0) and 15 individuals with severe NAFLD fibrosis or cirrhosis (F3-F4), matched for age, sex, body mass index, type 2 diabetes status, hemoglobin A1c, and use of diabetes medications. We used DESeq2 and Kruskal-Wallis test to identify miRNAs that were differentially expressed between NAFLD patients with or without fibrosis, adjusting for multiple testing using Bonferroni correction. We identified a total of 75 miRNAs showing statistically significant evidence (adjusted P value <0.05) for differential expression between the 2 groups, including 30 upregulated and 45 downregulated miRNAs. Quantitative reverse-transcription polymerase chain reaction analysis of selected miRNAs identified by sequencing validated 9 of 11 of the top differentially expressed miRNAs. We performed functional enrichment analysis of dysregulated miRNAs and identified several potential gene targets related to NAFLD-related fibrosis including hepatic fibrosis, hepatic stellate cell activation, transforming growth factor beta signaling, and apoptosis signaling. We identified forkhead box O3 and F-box WD repeat domain containing 7, E3 ubiquitin protein ligase (FBXW7) as potential targets of miR-182, and found that levels of forkhead box O3, but not FBXW7, were significantly decreased in fibrotic samples. These findings support a role for hepatic miRNAs in the pathogenesis of NAFLD-related fibrosis and yield possible new insight into the molecular mechanisms underlying the initiation and progression of liver fibrosis and cirrhosis.


Downey M.,Downey Obesity Report | Still C.,Geisinger Obesity Institute | Sharma A.M.,University of Alberta
Current Opinion in Endocrinology, Diabetes and Obesity | Year: 2011

Purpose of Review: Obesity continues to increase in prevalence in the USA and throughout the world. It is clearly a major contributor to morbidity and mortality. Unfortunately, effective prevention strategies are few. As a contributor to cardiovascular disease, obesity is an important treatment objective. However, before approval, all drugs must meet safety and efficacy concerns of the US Food and Drug Administration. Recent Findings: Since July 2010, the Food and Drug Administration's Endocrine and Metabolic Advisory Committee has reviewed three new drug applications and one previously approved drug for the treatment of obesity. This review examines in detail the Advisory Committee's consideration of the risk-benefit equation of the four drugs with a concentration on sibutramine and its key study, Sibutramine Cardiovascular Outcomes Trial. Summary: Future development of drugs for the treatment of obesity will be dependent on whether they can survive review for safety and effectiveness. The Food and Drug Administration continues to be highly concerned with proposed obesity drugs increasing cardiovascular or any risks and may require changes to clinical research protocols. Copyright © Lippincott Williams & Wilkins.

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