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Item 50 Years of Behavioral Science in Diabetes: A 2020 Vision of the Future(ADA, 2021) de Groot, Mary; Medicine, School of MedicineItem Analysis of INSPPIRE-2 Cohort: Risk Factors and Disease Burden in Children with Acute Recurrent or Chronic Pancreatitis(Wiley, 2022-11) Uc, Aliye; Cress, Gretchen A.; Wang, Fuchenchu; Abu-El-Haija, Maisam; Ellery, Kate M.; Fishman, Douglas S.; Gariepy, Cheryl E.; Gonska, Tanja; Lin, Tom K.; Liu, Quin Y.; Mehta, Megha; Maqbool, Asim; McFerron, Brian A.; Morinville, Veronique D.; Ooi, Chee Y.; Perito, Emily R.; Schwarzenberg, Sarah Jane; Sellers, Zachary M.; Serrano, Jose; Shah, Uzma; Troendle, David M.; Wilschanski, Michael; Zheng, Yuhua; Yuan, Ying; Lowe, Mark E.; Consortium for the Study of Chronic Pancreatitis, Diabetes and Pancreatic Cancer; Pediatrics, School of MedicineObjectives: To investigate risk factors and disease burden in pediatric acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP). Methods: Data were obtained from INternational Study group of Pediatric Pancreatitis: In search for a cuRE-2 (INSPPIRE-2), the largest multi-center prospective cohort study in pediatric patients with ARP or CP. Results: Of 689 children, 365 had ARP (53%), 324 CP (47%). CP was more commonly associated with female sex, younger age at first acute pancreatitis (AP) attack, Asian race, family history of CP, lower BMI%, genetic and obstructive factors, PRSS1 mutations and pancreas divisum. CFTR mutations, toxic-metabolic factors, medication use, hypertriglyceridemia, Crohn disease were more common in children with ARP. Constant or frequent abdominal pain, emergency room (ER) visits, hospitalizations, medical, endoscopic or surgical therapies were significantly more common in CP, episodic pain in ARP. 33.1% of children with CP had exocrine pancreatic insufficiency (EPI), 8.7% had diabetes mellitus. Compared to boys, girls were more likely to report pain impacting socialization and school, medical therapies, cholecystectomy, but no increased opioid use. There was no difference in race, ethnicity, age at first AP episode, age at CP diagnosis, duration of disease, risk factors, prevalence EPI or diabetes between boys and girls. Multivariate analysis revealed that family history of CP, constant pain, obstructive risk factors were predictors of CP. Conclusions: Children with family history of CP, constant pain or obstructive risk factors should raise suspicion for CP.Item Analyzing the Correlations between the Uninsured and Diabetes Prevalence Rates in Geographic Regions in the United States(IEEE, 2017-07) Luo, Xiao; Computer Information and Graphics Technology, School of Engineering and TechnologyThe increasing prevalence of diagnosed diabetes has drawn attentions of researchers in recently years. Research has been done in finding the correlations between diabetes prevalence with socioeconomic factors, obesity, social behaviors and so on. Since 2010, diabetes preventive services have been covered under health insurance plans in order to reduce diabetes burden and control the increasing of diabetes prevalence. In this study, a hierarchical clustering model is proposed by using Expectation-Maximization algorithm to investigate the correlations between the uninsured and diabetes prevalence rates in 3142 counties in United States for years from 2009 to 2013. The results identified geographic disparities in the uninsured and diabetes prevalence rates of individual years and over consecutive years.Item Antidepressant Medicine Use and Risk of Developing Diabetes During the Diabetes Prevention Program and Diabetes Prevention Program Outcomes Study(2010-12) Rubin, Richard R.; Ma, Yong; Peyrot, Mark; Marrero, David G.; Price, David W.; Barrett-Connor, Elizabeth; Knowler, William C.; for the Diabetes Prevention Program Research GroupOBJECTIVE To assess the association between antidepressant medicine use and risk of developing diabetes during the Diabetes Prevention Program (DPP) and Diabetes Prevention Program Outcomes Study (DPPOS). RESEARCH DESIGN AND METHODS DPP/DPPOS participants were assessed for diabetes every 6 months and for antidepressant use every 3 months in DPP and every 6 months in DPPOS for a median 10.0-year follow-up. RESULTS Controlled for factors associated with diabetes risk, continuous antidepressant use compared with no use was associated with diabetes risk in the placebo (adjusted hazard ratio 2.34 [95% CI 1.32–4.15]) and lifestyle (2.48 [1.45–4.22]) arms, but not in the metformin arm (0.55 [0.25–1.19]). CONCLUSIONS Continuous antidepressant use was significantly associated with diabetes risk in the placebo and lifestyle arms. Measured confounders and mediators did not account for this association, which could represent a drug effect or reflect differences not assessed in this study between antidepressant users and nonusers.Item The Art of Diabetes Prevention Education in Youth(Office of the Vice Chancellor for Research, 2014-04-11) Pike, Julie; Smith, Lisa; Clapp, Sarah; Hannon, Tamara S.; Kester, Laura; Lynch, Dustin; Kuhstoss, Courtney; Sanematsu, HelenBackground: The obesity epidemic has led to an increase in type 2 diabetes as well as the precursor condition “prediabetes.” Prediabetes is defined as blood glucose or hemoglobin A1c levels higher than normal, but not high enough for diabetes. Approximately 30% of obese adolescents in the U.S. have prediabetes. Youth with prediabetes have significantly increased risk for developing type 2 diabetes. Literature demonstrates the significant impact of modest weight loss and physical activity on the prevention or delay of type 2 diabetes. Education on diabetes risk and initiation of lifestyle change is the primary treatment modality. Materials are needed to more effectively educate youth on diabetes progression and risk reduction while using consistent information from evidence-based behavior change methods. Objective: The Youth Diabetes Prevention Clinic is collaborating with the Herron School of Art and Design and a professional design firm to develop an effective tool for communicating the importance of preventing type 2 diabetes while using adolescent-friendly language, visually exciting graphics and relevant messaging. Methods: The team consists of physicians who specialize in adolescent diabetes, a registered dietician, health educators, and graphic design professionals. The project is being completed in four phases: exploration, design, analysis, and refinement. Results: Exploration: The design professionals conducted key personnel interviews and a clinic site visit to determine the appropriate product design. Design: A 16-page booklet was created to incorporate the use of age-appropriate graphics, medical language in lay terms, and cohesive messaging in one package. Analysis: Usability will be measured through user-group testing, key personnel interviews, pre and post knowledge assessments and readiness to change scales. Refinement: Messaging will be revised based on analytical findings. Conclusions: This collaboration exemplifies the benefit of a multidisciplinary approach in the development of patient-centered education materials and provides a framework for others when developing age-specific health communication strategies.Item Association of Prediabetes and Diabetes With Stroke Symptoms The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study(2012-09) Carson, April P; Muntner, Paul; Kissella, Brett M; Kleindorfer, Dawn O.; Howard, Virginia J; Meschia, James F; Williams, Linda S.; Prineas, Ronald J; Howard, George; Safford, Monika MOBJECTIVE Stroke symptoms among individuals reporting no physician diagnosis of stroke are associated with an increased risk of future stroke. Few studies have assessed whether individuals with diabetes or prediabetes, but no physician diagnosis of stroke, have an increased prevalence of stroke symptoms. RESEARCH DESIGN AND METHODS This study included 25,696 individuals aged ≥45 years from the REasons for Geographic And Racial Differences in Stroke (REGARDS) study who reported no history of stroke or transient ischemic attack at baseline (2003–2007). Glucose measurements, medication use, and self-reported physician diagnosis were used to categorize participants into diabetes, prediabetes, or normal glycemia groups. The presence of six stroke symptoms was assessed using a validated questionnaire. RESULTS The prevalence of any stroke symptom was higher among participants with diabetes (22.7%) compared with those with prediabetes (15.6%) or normal glycemia (14.9%). In multivariable models, diabetes was associated with any stroke symptom (prevalence odds ratio [POR] 1.28 [95% CI 1.18–1.39]) and two or more stroke symptoms (1.26 [1.12–1.43]) compared with normal glycemia. In analyses of individual stroke symptoms, diabetes was associated with numbness (1.15 [1.03–1.29]), vision loss (1.52 [1.31–1.76]), half-vision loss (1.54 [1.30–1.84]), and lost ability to understand people (1.34 [1.12–1.61]) after multivariable adjustment. No association was present between prediabetes and stroke symptoms. CONCLUSIONS In this population-based study, almost one in four individuals with diabetes reported stroke symptoms, which suggests that screening for stroke symptoms in diabetes may be warranted.Item A Case of Refractory Hypoglycemia with DPP-IV Inhibitors in a Patient with CKD and Paraproteinemia(Society of Hospital Medicine, 2020-11-05) Lugo, Adrian; Cho, Elizabeth; MacKay, Keir; Thothala, NiranjanItem Changes in Skeletal Muscle PAK1 Levels Regulate Tissue Crosstalk to Impact Whole Body Glucose Homeostasis(Frontiers, 2022-02-10) Merz, Karla E.; Tunduguru, Ragadeepthi; Ahn, Miwon; Salunkhe, Vishal A.; Veluthakal, Rajakrishnan; Hwang, Jinhee; Bhattacharya, Supriyo; McCown, Erika M.; Garcia, Pablo A.; Zhou, Chunxue; Oh, Eunjin; Yoder, Stephanie M.; Elmendorf, Jeffrey S.; Thurmond, Debbie C.; Anatomy, Cell Biology & Physiology, School of MedicineSkeletal muscle accounts for ~80% of insulin-stimulated glucose uptake. The Group I p21–activated kinase 1 (PAK1) is required for the non-canonical insulin-stimulated GLUT4 vesicle translocation in skeletal muscle cells. We found that the abundances of PAK1 protein and its downstream effector in muscle, ARPC1B, are significantly reduced in the skeletal muscle of humans with type 2 diabetes, compared to the non-diabetic controls, making skeletal muscle PAK1 a candidate regulator of glucose homeostasis. Although whole-body PAK1 knockout mice exhibit glucose intolerance and are insulin resistant, the contribution of skeletal muscle PAK1 in particular was unknown. As such, we developed inducible skeletal muscle-specific PAK1 knockout (skmPAK1-iKO) and overexpression (skmPAK1-iOE) mouse models to evaluate the role of PAK1 in skeletal muscle insulin sensitivity and glucose homeostasis. Using intraperitoneal glucose tolerance and insulin tolerance testing, we found that skeletal muscle PAK1 is required for maintaining whole body glucose homeostasis. Moreover, PAK1 enrichment in GLUT4-myc-L6 myoblasts preserves normal insulin-stimulated GLUT4 translocation under insulin resistance conditions. Unexpectedly, skmPAK1-iKO also showed aberrant plasma insulin levels following a glucose challenge. By applying conditioned media from PAK1-enriched myotubes or myoblasts to β-cells in culture, we established that a muscle-derived circulating factor(s) could enhance β-cell function. Taken together, these data suggest that PAK1 levels in the skeletal muscle can regulate not only skeletal muscle insulin sensitivity, but can also engage in tissue crosstalk with pancreatic β-cells, unveiling a new molecular mechanism by which PAK1 regulates whole-body glucose homeostasis.Item Comparison of Deep Learning based Concept Representations for Biomedical Document Clustering(IEEE, 2018) Shah, Setu; Luo, Xiao; Computer and Information Science, School of ScienceIn this research, document representations based on distributed representations of the concepts along with new weighting schemes for the documents are explored. The baseline weighting scheme is the traditional Term Frequency-Inverse Document Frequency (TF-IDF) of the concepts, whereas, the other two newly proposed ones consider both local content using the TF-IDF and associations between concepts. The distributed representations of the concepts are measured using a deep learning algorithm. The evaluation of the proposed document representations is based on the k-means clustering results. The results show that document representation based on TF-IDF in combination with the term based distributed representations for concepts outperforms the other two based on the returned evaluation metrics - F1-measure (80.21%) and Purity (77.1%).Item Contribution of Environment and Genetics to Pancreatic Cancer Susceptibility(Public Library of Science, 2014-03-20) Hocevar, Barbara A.; Kamendulis, Lisa M.; Pu, Xinzhu; Perkins, Susan M.; Wang, Zheng-Yu; Johnston, Erica L.; DeWitt, John M.; Li, Lang; Loehrer, Patrick J.; Klaunig, James E.; Chiorean, E. Gabriela; Medicine, School of MedicineSeveral risk factors have been identified as potential contributors to pancreatic cancer development, including environmental and lifestyle factors, such as smoking, drinking and diet, and medical conditions such as diabetes and pancreatitis, all of which generate oxidative stress and DNA damage. Oxidative stress status can be modified by environmental factors and also by an individual's unique genetic makeup. Here we examined the contribution of environment and genetics to an individual's level of oxidative stress, DNA damage and susceptibility to pancreatic cancer in a pilot study using three groups of subjects: a newly diagnosed pancreatic cancer group, a healthy genetically-unrelated control group living with the case subject, and a healthy genetically-related control group which does not reside with the subject. Oxidative stress and DNA damage was evaluated by measuring total antioxidant capacity, direct and oxidative DNA damage by Comet assay, and malondialdehyde levels. Direct DNA damage was significantly elevated in pancreatic cancer patients (age and sex adjusted mean ± standard error: 1.00±0.05) versus both healthy unrelated and related controls (0.70±0.06, p<0.001 and 0.82±0.07, p = 0.046, respectively). Analysis of 22 selected SNPs in oxidative stress and DNA damage genes revealed that CYP2A6 L160H was associated with pancreatic cancer. In addition, DNA damage was found to be associated with TNFA −308G>A and ERCC4 R415Q polymorphisms. These results suggest that measurement of DNA damage, as well as select SNPs, may provide an important screening tool to identify individuals at risk for development of pancreatic cancer.