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Item Association between cardiometabolic risk factors and COVID-19 susceptibility, severity and mortality: a review(Springer, 2021-06-26) Sharifi, Yasaman; Payab, Moloud; Mohammadi-Vajari, Erfan; Aghili, Seyed Morsal Mosallami; Sharifi, Farshad; Mehrdad, Neda; Kashani, Elham; Shadman, Zhaleh; Larijani, Bagher; Ebrahimpur, Mahbube; Center for Diabetes and Metabolic Diseases, IU School of MedicineThe novel coronavirus, which began spreading from China Wuhan and gradually spreaded to most countries, led to the announcement by the World Health Organization on March 11, 2020, as a new pandemic. The most important point presented by the World Health Organization about this disease is to better understand the risk factors that exacerbate the course of the disease and worsen its prognosis. Due to the high majority of cardio metabolic risk factors like obesity, hypertension, diabetes, and dyslipidemia among the population over 60 years old and higher, these cardio metabolic risk factors along with the age of these people could worsen the prognosis of the coronavirus disease of 2019 (COVID-19) and its mortality. In this study, we aimed to review the articles from the beginning of the pandemic on the impression of cardio metabolic risk factors on COVID-19 and the effectiveness of COVID-19 on how to manage these diseases. All the factors studied in this article, including hypertension, diabetes mellitus, dyslipidemia, and obesity exacerbate the course of Covid-19 disease by different mechanisms, and the inflammatory process caused by coronavirus can also create a vicious cycle in controlling these diseases for patients.Item Association of Pancreatic Steatosis With Chronic Pancreatitis, Obesity, and Type 2 Diabetes Mellitus(Lippincott, Williams & Wilkins, 2019-03) Tirkes, Temel; Jeon, Christie Y.; Li, Liang; Joon, Aron Y.; Seltman, Ted A.; Sankar, Meghana; Persohn, Scott A.; Territo, Paul R.; Radiology and Imaging Sciences, School of MedicineObjective: The aim of this study was to determine the association of the pancreatic steatosis with obesity, chronic pancreatitis (CP), and type 2 diabetes mellitus. Methods: Patients (n = 118) were retrospectively identified and categorized into no CP (n = 60), mild (n = 21), moderate (n = 27), and severe CP (n = 10) groups based on clinical history and magnetic resonance cholangiopancreatography using the Cambridge classification as the diagnostic standard. Visceral and subcutaneous compartments were manually segmented, and fat tissue was quantitatively measured on axial magnetic resonance imaging. Results: Pancreatic fat fraction showed a direct correlation with fat within the visceral compartment (r = 0.54). Patients with CP showed higher visceral fat (P = 0.01) and pancreatic fat fraction (P < 0.001): mild, 24%; moderate, 23%; severe CP, 21%; no CP group, 15%. Patients with type 2 diabetes mellitus showed higher pancreatic steatosis (P = 0.03) and higher visceral (P = 0.007) and subcutaneous fat (P = 0.004). Interobserver variability of measuring fat by magnetic resonance imaging was excellent (r ≥ 0.90–0.99). Conclusions: Increased visceral adipose tissue has a moderate direct correlation with pancreatic fat fraction. Chronic pancreatitis is associated with higher pancreatic fat fraction and visceral fat. Type 2 diabetes mellitus is associated with higher pancreatic fat fraction and visceral and subcutaneous adiposity.Item Biomarkers of islet beta cell stress and death in type 1 diabetes(Springer Nature, 2018-11) Sims, Emily K.; Evans-Molina, Carmella; Tersey, Sarah A.; Eizirik, Decio L.; Mirmira, Raghavendra G.; Pediatrics, School of MedicineRecent work on the pathogenesis of type 1 diabetes has led to an evolving recognition of the heterogeneity of this disease, both with regards to clinical phenotype and responses to therapies to prevent or revert diabetes. This heterogeneity not only limits efforts to accurately predict clinical disease but also is reflected in differing responses to immunomodulatory therapeutics. Thus, there is a need for robust biomarkers of beta cell health, which could provide insight into pathophysiological differences in disease course, improve disease prediction, increase the understanding of therapeutic responses to immunomodulatory interventions and identify individuals most likely to benefit from these therapies. In this review, we outline current literature, limitations and future directions for promising circulating markers of beta cell stress and death in type 1 diabetes, including markers indicating abnormal prohormone processing, circulating RNAs and circulating DNAs.Item Clinician Perceptions of a Computerized Decision Support System for Pediatric Type 2 Diabetes Screening(Thieme, 2020-03) El Mikati, Hala K.; Yazel-Smith, Lisa; Grout, Randall W.; Downs, Stephen M.; Carroll, Aaron E.; Hannon, Tamara S.; Pediatrics, School of MedicineObjective: With the increasing prevalence of type 2 diabetes (T2D) in youth, primary care providers must identify patients at high risk and implement evidence-based screening promptly. Clinical decision support systems (CDSSs) provide clinicians with personalized reminders according to best evidence. One example is the Child Health Improvement through Computer Automation (CHICA) system, which, as we have previously shown, significantly improves screening for T2D. Given that the long-term success of any CDSS depends on its acceptability and its users' perceptions, we examined what clinicians think of the CHICA diabetes module. Methods: CHICA users completed an annual quality improvement and satisfaction questionnaire. Between May and August of 2015 and 2016, the survey included two statements related to the T2D-module: (1) "CHICA improves my ability to identify patients who might benefit from screening for T2D" and (2) "CHICA makes it easier to get the lab tests necessary to identify patients who have diabetes or prediabetes." Answers were scored using a 5-point Likert scale and were later converted to a 2-point scale: agree and disagree. The Pearson chi-square test was used to assess the relationship between responses and the respondents. Answers per cohort were compared using the Mann-Whitney U-test. Results: The majority of respondents (N = 60) agreed that CHICA improved their ability to identify patients who might benefit from screening but disagreed as to whether it helped them get the necessary laboratories. Scores were comparable across both years. Conclusion: CHICA was endorsed as being effective for T2D screening. Research is needed to improve satisfaction for getting laboratories with CHICA.Item Comparative risk of severe hypoglycemia among concomitant users of thiazolidinedione antidiabetic agents and antihyperlipidemics(Elsevier, 2016-05) Leonard, Charles E.; Han, Xu; Bilker, Warren B.; Flory, James H.; Brensinger, Colleen M.; Flockhart, David A.; Gagne, Joshua J.; Cardillo, Serena; Hennessy, Sean; Department of Medicine, IU School of MedicineWe conducted high-dimensional propensity score-adjusted cohort studies to examine whether thiazolidinedione use with a statin or fibrate was associated with an increased risk of severe hypoglycemia. We found that concomitant therapy with a thiazolidinedione+fibrate was associated with a generally delayed increased risk of severe hypoglycemia.Item Depression and Anxiety Screens as Simultaneous Predictors of 10-Year Incidence of Diabetes Mellitus in Older Adults in Primary Care(Wiley, 2017-02) Khambaty, Tasneem; Callahan, Christopher M.; Perkins, Anthony J.; Stewart, Jesse C.; Medicine, School of MedicineOBJECTIVES: To examine depression and anxiety screens and their individual items as simultaneous predictors of incident diabetes mellitus. DESIGN: Ten-year follow-up study of individuals screened for the Improving Mood-Promoting Access to Collaborative Treatment (IMPACT) trial. SETTING: Two large urban primary care clinics in Indianapolis, Indiana. PARTICIPANTS: Diverse sample (53% African American, 80% of lower socioeconomic status) of 2,156 older adults initially free of diabetes mellitus. MEASUREMENTS: Depression and anxiety screens were completed during routine primary care visits between 1999 and 2001. Incident diabetes mellitus data were obtained from an electronic medical record system and the Centers for Medicare and Medicaid Services analytical files though 2009. RESULTS: Over the 10-year period, 558 (25.9%) participants had diabetes mellitus onset. Cox proportional hazards models adjusted for demographic and diabetes mellitus risk factors revealed that a positive screen for anxiety, but not for depression, predicted incident diabetes mellitus when entered into separate models (anxiety: hazard ratio (HR) = 1.36, 95% confidence interval (CI) = 1.15-1.61, P < .001; depression: HR = 1.18, 95% CI = 0.95-1.46, P = .13) and when entered simultaneously into one model (anxiety: HR = 1.35, 95% CI = 1.12-1.61, P < .001; depression: HR = 1.04, 95% CI = 0.83-1.31, P = .73). The feeling anxious (P = .03) and the worry (P = .02) items predicted incident diabetes mellitus independent of the depression screen. CONCLUSION: These findings suggest that screening positive for anxiety is a risk factor for diabetes mellitus in older adults independent of depression and traditional diabetes mellitus risk factors. Anxiety requires greater consideration and awareness in the context of diabetes mellitus risk assessment and primary prevention.Item Editorial: Acute Kidney Injury: It's Not Just Acute, and It's Not Just the Kidneys(Frontiers Media, 2021-11-15) Soranno, Danielle E.; Deep, Akash; Gist, Katja M.; Zappitelli, Michael; Pediatrics, School of MedicineItem The effect of adverse housing and neighborhood conditions on the development of diabetes mellitus among middle-aged African Americans(Oxford University Press, 2007-08-15) Schootman, Mario; Andresen, Elena M.; Wolinsky, Fredric D.; Malmstrom, Theodore K.; Miller, J. Philip; Yan, Yan; Miller, Douglas K.; Department of Medicine, IU School of MedicineThe authors examined the associations of observed neighborhood (block face) and housing conditions with the incidence of diabetes by using data from 644 subjects in the African-American Health Study (St. Louis area, Missouri). They also investigated five mediating pathways (health behavior, psychosocial, health status, access to medical care, and sociodemographic characteristics) if significant associations were identified. The external appearance of the block the subjects lived on and housing conditions were rated as excellent, good, fair, or poor. Subjects reported about neighborhood desirability. Self-reported diabetes was obtained at baseline and 3 years later. Of 644 subjects without self-reported diabetes, 10.3% reported having diabetes at the 3-year follow-up. Every housing condition rated as fair-poor was associated with an increased risk of diabetes, with odds ratios ranging from 2.53 (95% confidence interval: 1.47, 4.34 for physical condition inside the building) to 1.78 (95% confidence interval: 1.03, 3.07 for cleanliness inside the building) in unadjusted analyses. No association was found between any of the block face conditions or perceived neighborhood conditions and incident diabetes. The odds ratios for the five housing conditions were unaffected when adjusted for the mediating pathways. Poor housing conditions appear to be an independent contributor to the risk of incident diabetes in urban, middle-aged African Americans.Item F-box protein-32 down-regulates small-conductance calcium-activated potassium channel 2 in diabetic mouse atria(Elsevier, 2019-03-15) Ling, Tian-You; Yi, Fu; Lu, Tong; Wang, Xiao-Li; Sun, Xiaojing; Willis, Monte S.; Wu, Li-Qun; Shen, Win-Kuang; Adelman, John P.; Lee, Hon-Chi; Pathology and Laboratory Medicine, School of MedicineDiabetes mellitus (DM) is an independent risk factor for atrial fibrillation, but the underlying ionic mechanism for this association remains unclear. We recently reported that expression of the small-conductance calcium-activated potassium channel 2 (SK2, encoded by KCCN2) in atria from diabetic mice is significantly down-regulated, resulting in reduced SK currents in atrial myocytes from these mice. We also reported that the level of SK2 mRNA expression is not reduced in DM atria but that the ubiquitin-proteasome system (UPS), a major mechanism of intracellular protein degradation, is activated in vascular smooth muscle cells in DM. This suggests a possible role of the UPS in reduced SK currents. To test this possibility, we examined the role of the UPS in atrial SK2 down-regulation in DM. We found that a muscle-specific E3 ligase, F-box protein 32 (FBXO-32, also called atrogin-1), was significantly up-regulated in diabetic mouse atria. Enhanced FBXO-32 expression in atrial cells significantly reduced SK2 protein expression, and siRNA-mediated FBXO-32 knockdown increased SK2 protein expression. Furthermore, co-transfection of SK2 with FBXO-32 complementary DNA in HEK293 cells significantly reduced SK2 expression, whereas co-transfection with atrogin-1ΔF complementary DNA (a nonfunctional FBXO-32 variant in which the F-box domain is deleted) did not have any effects on SK2. These results indicate that FBXO-32 contributes to SK2 down-regulation and that the F-box domain is essential for FBXO-32 function. In conclusion, DM-induced SK2 channel down-regulation appears to be due to an FBXO-32-dependent increase in UPS-mediated SK2 protein degradation.Item Getting A Leg Up on Cell Therapy for Critical Limb Ischemia(American Heart Association, 2017-04-14) Wang, S. Keisin; Murphy, Michael P.; Surgery, School of Medicine