Browsing by Subject "Obesity"
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Item 12-Lipoxygenase Promotes Obesity-Induced Oxidative Stress in Pancreatic Islets(American Society for Microbiology (ASM), 2014-10) Tersey, Sarah A.; Maier, Bernhard; Nishiki, Yurika; Maganti, Aarthi V.; Nadler, Jerry L.; Mirmira, Raghavendra G.; Department of Pediatrics, IU School of MedicineHigh-fat diets lead to obesity, inflammation, and dysglycemia. 12-Lipoxygenase (12-LO) is activated by high-fat diets and catalyzes the oxygenation of cellular arachidonic acid to form proinflammatory intermediates. We hypothesized that 12-LO in the pancreatic islet is sufficient to cause dysglycemia in the setting of high-fat feeding. To test this, we generated pancreas-specific 12-LO knockout mice and studied their metabolic and molecular adaptations to high-fat diets. Whereas knockout mice and control littermates displayed identical weight gain, body fat distribution, and macrophage infiltration into fat, knockout mice exhibited greater adaptive islet hyperplasia, improved insulin secretion, and complete protection from dysglycemia. At the molecular level, 12-LO deletion resulted in increases in islet antioxidant enzymes Sod1 and Gpx1 in response to high-fat feeding. The absence or inhibition of 12-LO led to increases in nuclear Nrf2, a transcription factor responsible for activation of genes encoding antioxidant enzymes. Our data reveal a novel pathway in which islet 12-LO suppresses antioxidant enzymes and prevents the adaptive islet responses in the setting of high-fat diets.Item 2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Atrial Fibrillation(Elsevier, 2024) Joglar, José A.; Chung, Mina K.; Armbruster, Anastasia L.; Benjamin, Emelia J.; Chyou, Janice Y.; Cronin, Edmond M.; Deswal, Anita; Eckhardt, Lee L.; Goldberger, Zachary D.; Gopinathannair, Rakesh; Gorenek, Bulent; Hess, Paul L.; Hlatky, Mark; Hogan, Gail; Ibeh, Chinwe; Indik, Julia H.; Kido, Kazuhiko; Kusumoto, Fred; Link, Mark S.; Linta, Kathleen T.; Marcus, Gregory M.; McCarthy, Patrick M.; Patel, Nimesh; Patton, Kristen K.; Perez, Marco V.; Piccini, Jonathan P.; Russo, Andrea M.; Sanders, Prashanthan; Streur, Megan M.; Thomas, Kevin L.; Times, Sabrina; Tisdale, James E.; Valente, Anne Marie; Van Wagoner, David R.; Pharmacology and Toxicology, School of MedicineAim: The "2023 ACC/AHA/ACCP/HRS Guideline for the Diagnosis and Management of Patients With Atrial Fibrillation" provides recommendations to guide clinicians in the treatment of patients with atrial fibrillation. Methods: A comprehensive literature search was conducted from May 12, 2022, to November 3, 2022, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, the Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline. Additional relevant studies, published through November 2022, during the guideline writing process, were also considered by the writing committee and added to the evidence tables, where appropriate. Structure: Atrial fibrillation is the most sustained common arrhythmia, and its incidence and prevalence are increasing in the United States and globally. Recommendations from the "2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" and the "2019 AHA/ACC/HRS Focused Update of the 2014 AHA/ACC/HRS Guideline for the Management of Patients With Atrial Fibrillation" have been updated with new evidence to guide clinicians. In addition, new recommendations addressing atrial fibrillation and thromboembolic risk assessment, anticoagulation, left atrial appendage occlusion, atrial fibrillation catheter or surgical ablation, and risk factor modification and atrial fibrillation prevention have been developed.Item 4405 Chronic Disease in Indiana – Using a Community Health Matrix to Determine Health Factors for Indiana Counties(Cambridge University Press, 2020-07-29) Wiehe, Sarah; Zych, Aaron; Hinshaw, Karen; Alley, Ann; Claxton, Gina; Savaiano, Dennis; Pediatrics, School of MedicineOBJECTIVES/GOALS: The goal of this project was to inform four chronic disease initiatives, working together on the team Connections IN Health, and counties in Indiana on certain areas of need to assist them in collaborative planning. The chronic diseases focused on include diabetes, cardiovascular disease, stroke, asthma, lung cancer and obesity. METHODS/STUDY POPULATION: Chronic disease health outcomes and social determinants of health indicators were identified in all 92 Indiana counties. Counties were compared by composite z scores in a matrix to determine the 23 counties with the poorest health statistics for diabetes, cardiovascular disease, stroke, asthma, lung cancer, obesity and life expectancy. Qualitative data were used to identify local health coalitions that have the capacity and desire to work with Connections IN Health to improve these health outcomes. With input from partners, the counties were narrowed to 10 that were identified as those with the most need in the specific areas of chronic disease that the initiatives focus on. The team will begin listening sessions with two of these counties to identify strategic partnerships, funding sources, and evidence-based programs to address community-identified health priorities. RESULTS/ANTICIPATED RESULTS: The 23 counties with the poorest health outcomes related to chronic disease and factors were Blackford, Clark, Clay, Fayette, Fulton, Grant, Greene, Howard, Jay, Jennings, Knox, Lake, LaPorte, Madison, Marion, Pike, Scott, Starke, Sullivan, Vanderburgh, Vermillion, Vigo, and Washington. There was significant overlap in low z score rankings for individual health and social determinants of health measures among these 23 counties. The following 10 counties were selected for focus in the next five years based on partner input: Blackford, Clay, Grant, Jennings, Lake, Madison, Marion, Starke, Vermillion, and Washington. The Connections IN Health team has initiated listening sessions in Grant and Vermillion Counties (with data for presentation at the ACTS meeting). DISCUSSION/SIGNIFICANCE OF IMPACT: This mixed methods approach using existing data and partner input on county capacity/readiness directed Connections IN Health to counties with the most need for coalition efforts. Engagement within each county will inform next steps (e.g., capacity building, partnership development, applications for funding, implementation of evidence-based programs) and specific health focus area(s).Item A Call for Person-Centered Language with Regards to Weight(Elsevier, 2024) Cheng, Erika R.; Wilkinson, Tracey A.; Pediatrics, School of MedicineItem A co-designed, community-based intensive health behavior intervention promotes participation and engagement in youth with risk factors for type 2 diabetes(Frontiers Media, 2023-12-01) Pike, Julie M.; Haberlin-Pittz, Kathryn M.; Alharbi, Basmah S.; Perkins, Susan M.; Hannon, Tamara S.; Pediatrics, School of MedicineBackground: Obesity among youth (children and adolescents) is associated with increased risk for youth-onset type 2 diabetes. Lifestyle change can delay or prevent the development of type 2 diabetes, yet real-world implementation of health behavior recommendations is challenging. We previously engaged youth with risk factors for type 2 diabetes, their caregivers, and professionals in a human-centered design study to co-design a lifestyle change program. Here we report the outcomes for this 16-week co-designed lifestyle change program for youth at risk for T2D and their caregivers. Research design and methods: This single-arm family-based cohort study included youth aged 7-18 years, with BMI ≥85th percentile (overweight or obese) and at least one additional risk factor for type 2 diabetes, and their caregivers. Clinical (BMI, HbA1c), self-reported physical activity, and quality of life outcomes were evaluated at baseline (B), post-intervention (M4), and 1 year (M12) following the intervention. Results: Seventy-eight youth (mean age 12.4 ± 2.7y, 67% female, 37.8% white) and 65 caregivers were included in the data analysis. Youth baseline BMI z-scores (2.26 ± 0.47) and HbA1c (5.3 ± 0.3) were unchanged at follow up time points [BMI z-scores M4 (2.25 ± 0.52), M12 (2.16 ± 0.58), p-value 0.46], [HbA1c M4 (5.3 ± 0.3), M12 (5.2 ± 0.3), p-value (0.04)]. Youth reported increased physical activity at M4 (p = 0.004), but not at M12. Youth quality of life scores increased at M12 (p=0.01). Families who attended at least one session (n=41) attended an average of 9 out of 16 sessions, and 37 percent of families attended 13 or more sessions. Conclusion: A co-designed, community-based lifestyle intervention promotes increased physical activity, improved quality of life, maintenance of BMI z-scores and HbA1c, and engagement in youth with risk factors for T2D.Item Abdominal visceral and subcutaneous adipose tissue associations with postmenopausal breast cancer incidence(Oxford University Press, 2025) Bea, Jennifer W.; Ochs-Balcom, Heather M.; Valencia, Celina I.; Chen, Zhao; Blew, Robert M.; Lind, Kimberly E.; Caan, Bette J.; Roe, Denise J.; Rohan, Thomas E.; Reeves, Katherine W.; Manson, JoAnn E.; Ballinger, Tarah; Reding, Kerryn W.; Follis, Shawna; Ziller, Shelby G.; Odegaard, Andrew O.; Medicine, School of MedicineBackground: Obesity, classified by body mass index (BMI), is associated with higher postmenopausal breast cancer (BCa) risk. Yet, the associations between abdominal visceral (VAT) and subcutaneous adipose tissue (SAT) with BCa are unclear. Methods: We assessed BCa associations with abdominal VAT and SAT in a prospective cohort of postmenopausal women without a history of cancer and with 27 years follow-up (N = 9950), during which all new cancers were adjudicated. Dual-energy x-ray absorptiometry scans assessed adiposity at baseline, year 3, and year 6. Competing-risks multivariable sub-hazard ratios (SHR), with adjustments for sociodemographic, behavioral, reproductive, and anthropometric characteristics, were estimated for baseline and time-dependent associations between VAT, SAT, and incident BCa. Results: Participants averaged 63.3 ± 7.4 years of age and a BMI of 28.20 ± 5.72 kg/m2 at baseline. The models included 738 incident BCa case patients (N = 593 invasive; N = 145 in situ). Baseline VAT and SAT area were associated with statistically significantly increased BCa risk, by 36% and 19%, respectively. Increasing VAT/SAT ratio was associated with an 8% increase in incident BCa. Time-dependent models produced similar results. VAT and VAT/SAT associated BCa risk was highest for African American/Black women, although not statistically significantly different from other groups. Quartiles (Q) of VAT/SAT were also explored; the SHR for Q4 compared with Q1 was 1.49 (95% CI = 1.18 to 1.87). Conclusion: Higher abdominal VAT and SAT are associated with an increased risk of postmenopausal BCa, and VAT/SAT may provide a distinctive risk estimate. Potential racial and ethnic differences require replication in a larger sample.Item Acceptability of Exercise in Urban Emergency Department Patients With Metabolic Syndrome, Including a Subset With Venous Thromboembolism(Sage, 2022-03-02) Stewart, Lauren K.; Kline, Jeffrey A.; Emergency Medicine, School of MedicineMetabolic syndrome (MetS) afflicts more than one-third of US adults. In venous thromboembolism (VTE), MetS increases the risk of recurrence and severity of the post-pulmonary embolism syndrome, disproportionately affecting persons of color in urban settings. Exercise can positively modulate components of MetS. Our objective was to survey a sample of urban emergency department (ED) patients with MetS on their exercise habits and interest in increasing activity levels and to compare ± VTE patients. This survey study consisted of: (1) International Physical Activity Questionnaire, and (2) Likert scale gauging interest in increasing activity levels. Any adult ED patient with a composite MetS profile was included. We surveyed 247 patients with an average age of 59 years and 57% reported Black race. Only 9% met recommendations for vigorous exercise and 28% for moderate activity, with no significant difference in the 18% with prior VTE. Fifty-seven percent responded positively regarding motivation in increasing activity. This survey presents novel data supporting the need and feasibility of an interventional study examining exercise as an adjuvant therapy in patients with MetS and VTE.Item Accommodating patients with obesity in ambulatory care: A clinical environment checklist(Wiley, 2024-09-04) Boland, Wesley; Li, Wendy S.; Dilly, Christen K.; Surgery, School of MedicineObjective: Individuals with obesity face unique challenges when visiting healthcare providers, including inadequate equipment. These negative care experiences, often exacerbated by weight stigma, frequently lead to mistrust and reluctance to seek future care. Currently, few instruments exist to ensure that an ambulatory clinic is welcoming to patients with obesity. The following clinical environment checklist was created with an aim to identify weaknesses in accommodating individuals of size. Methods: A checklist of equipment considered ideal for the care of patients with obesity was developed through a comprehensive review of the literature and feedback from office staff. Eight ambulatory clinics within an urban Midwest setting were assessed, focusing on their accommodations for patients with obesity. Feedback from clinic staff was incorporated to further refine the checklist. Results: Common equipment deficiencies included extra-large blood pressure cuffs, wheelchair-accessible scales, 2XL gowns, and adequate seat dimensions in the waiting area. Healthcare workers reported moral distress for their patients when unable to provide proper care due to these limitations. Newly constructed clinics exhibited better-equipped facilities for patients with obesity. Conclusions: Many clinics lack proper equipment to accommodate patients with obesity, resulting in negative care experiences. This clinical environment checklist can identify problem areas and provide solutions to create more welcoming environments, encouraging future care-seeking behaviors.Item ACE2 Deficiency Worsens Epicardial Adipose Tissue Inflammation and Cardiac Dysfunction in Response to Diet-Induced Obesity(American Diabetes Association, 2016-01) Patel, Vaibhav B.; Mori, Jun; McLean, Brent A.; Basu, Ratnadeep; Das, Subhash K.; Ramprasath, Tharmarajan; Parajuli, Nirmal; Penninger, Josef M.; Grant, Maria B.; Lopaschuk, Gary D.; Oudit, Gavin Y.; Department of Ophthalmology, IU School of MedicineObesity is increasing in prevalence and is strongly associated with metabolic and cardiovascular disorders. The renin-angiotensin system (RAS) has emerged as a key pathogenic mechanism for these disorders; angiotensin (Ang)-converting enzyme 2 (ACE2) negatively regulates RAS by metabolizing Ang II into Ang 1-7. We studied the role of ACE2 in obesity-mediated cardiac dysfunction. ACE2 null (ACE2KO) and wild-type (WT) mice were fed a high-fat diet (HFD) or a control diet and studied at 6 months of age. Loss of ACE2 resulted in decreased weight gain but increased glucose intolerance, epicardial adipose tissue (EAT) inflammation, and polarization of macrophages into a proinflammatory phenotype in response to HFD. Similarly, human EAT in patients with obesity and heart failure displayed a proinflammatory macrophage phenotype. Exacerbated EAT inflammation in ACE2KO-HFD mice was associated with decreased myocardial adiponectin, decreased phosphorylation of AMPK, increased cardiac steatosis and lipotoxicity, and myocardial insulin resistance, which worsened heart function. Ang 1-7 (24 µg/kg/h) administered to ACE2KO-HFD mice resulted in ameliorated EAT inflammation and reduced cardiac steatosis and lipotoxicity, resulting in normalization of heart failure. In conclusion, ACE2 plays a novel role in heart disease associated with obesity wherein ACE2 negatively regulates obesity-induced EAT inflammation and cardiac insulin resistance.Item Acute Changes in Sleep Duration on Eating Behaviors and Appetite-Regulating Hormones in Overweight/Obese Adults(Taylor & Francis, 2015) Hart, Chantelle N.; Carskadon, Mary A.; Demos, Kathryn E.; Van Reen, Eliza; Sharkey, Katherine M.; Raynor, Hollie A.; Considine, Robert V.; Jones, Richard N.; Wing, Rena R.; Department of Medicine, IU School of MedicineThere is considerable interest in the role of sleep in weight regulation, yet few studies have examined this relationship in overweight/obese (OW/OB) adults. Using a within-subject, counterbalanced design, 12 OW/OB women were studied in lab with two nights of short (5 hr time in bed [TIB]) and two nights of long (9 hr TIB) sleep. Hunger, consumption at a buffet, and fasting hormone levels were obtained. Significant polysomnographic differences occurred between conditions in total sleep time and sleep architecture (ps < .001). Percent energy from protein at the buffet increased following short sleep. No differences were observed for total energy intake or measured hormones. Further research is needed to determine how lengthening sleep impacts weight regulation in OW/OB adults.