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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; Medical and Molecular Genetics, 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 Burden of Fatty Liver and Hepatic Fibrosis in Persons with HIV: A Diverse Cross-sectional US Multicenter Study(Wolters Kluwer, 2023) Gawrieh, Samer; Lake, Jordan E.; Debroy, Paula; Sjoquist, Julia A.; Robison, Montreca; Tann, Mark; Akisik, Fatih; Bhamidipalli, Surya S.; Saha, Chandan K.; Zachary, Kimon; Robbins, Gregory K.; Gupta, Samir K.; Chung, Raymond T.; Chalasani, Naga; Corey, Kathleen E.; Radiology and Imaging Sciences, School of MedicineBackground aims: The current prevalence of fatty liver disease (FLD) due to alcohol-associated (AFLD) and nonalcoholic (NAFLD) origins in US persons with HIV (PWH) is not well defined. We prospectively evaluated the burden of FLD and hepatic fibrosis in a diverse cohort of PWH. Approach results: Consenting participants in outpatient HIV clinics in 3 centers in the US underwent detailed phenotyping, including liver ultrasound and vibration-controlled transient elastography for controlled attenuation parameter and liver stiffness measurement. The prevalence of AFLD, NAFLD, and clinically significant and advanced fibrosis was determined. Univariate and multivariate logistic regression models were used to evaluate factors associated with the risk of NAFLD. Of 342 participants, 95.6% were on antiretroviral therapy, 93.9% had adequate viral suppression, 48.7% (95% CI 43%-54%) had steatosis by ultrasound, and 50.6% (95% CI 45%-56%) had steatosis by controlled attenuation parameter ≥263 dB/m. NAFLD accounted for 90% of FLD. In multivariable analysis, old age, higher body mass index, diabetes, and higher alanine aminotransferase, but not antiretroviral therapy or CD4 + cell count, were independently associated with increased NAFLD risk. In all PWH with fatty liver, the frequency of liver stiffness measurement 8-12 kPa was 13.9% (95% CI 9%-20%) and ≥12 kPa 6.4% (95% CI 3%-11%), with a similar frequency of these liver stiffness measurement cutoffs in NAFLD. Conclusions: Nearly half of the virally-suppressed PWH have FLD, 90% of which is due to NAFLD. A fifth of the PWH with FLD has clinically significant fibrosis, and 6% have advanced fibrosis. These data lend support to systematic screening for high-risk NAFLD in PWH.Item Cardiometabolic health after first pregnancy: Associations with social determinants of health. A nuMoM2b-HHS study(Elsevier, 2022) Bello, N. A.; Moore, J.; Miller, E. C.; Tom, S. E.; Bairey Merz, C. N.; Haas, D. M.; Ferries-Rowe, E. A.; Grobman, W. A.; Greenland, P.; Khan, S. S.; Kim, J. K.; Chung, J. H.; Huynh, P. L. L.; Varagic, J.; McNeil, R. B.; Parker, C. B.; Wapner, R.; NICHD nuMoM2b; NHLBI nuMoM2b Heart Health Study Networks; Obstetrics and Gynecology, School of MedicineStudy objective: This study sought to evaluate the associations between social determinants of health (SDOH) at the time of first pregnancy and subsequent cardiometabolic health, defined as the development of metabolic syndrome. Design: nuMoM2b-HHS (Nulliparous Pregnancy Outcomes Study- Monitoring Mothers-to-Be-Heart Health Study) is an ongoing prospective cohort study. Setting: Eight academic medical centers enrolled and continue to follow participants. Participants: 4484 participants followed a mean of 3.2 years from the time of their first pregnancy. Interventions: N/a. Main outcome measure: Unadjusted and adjusted Poisson regression models with robust standard errors were used to obtain relative risks and 95% confidence intervals estimating the risk of metabolic syndrome for each baseline SDOH. In secondary analyses we examined the associations between SDOH and incident hypertension, obesity, and diabetes mellitus. Results: Metabolic syndrome developed in 13.6% of participants. Higher socioeconomic position at the time of pregnancy was associated with lower rates of metabolic syndrome [income > 200% poverty level aRR 0.55 (95% CI, 0.42-0.71), attainment of a bachelor's degree aRR 0.62 (0.46-0.84) or higher aRR 0.50 (0.35-0.71)], while being single [aRR 1.45 (95% CI, 1.18-1.77)] and having low health literacy were associated with a greater risk of metabolic syndrome [aRR 1.98 (95% CI, 1.28-3.07)]. Conclusions: Over a short interval following first pregnancy, participants accumulated high proportions of cardiovascular risk factors and metabolic syndrome, with some risk associated with SDOH. The impact of interventions addressing SDOH in pregnant people on cardiometabolic health should be tested as a means of reducing health inequities at the population level.Item Characteristics, clinical laboratory, histopathology, and outcomes of glycogenic hepatopathy in children(Wolters Kluwer, 2024) Jarasvaraparn, Chaowapong; González, Iván A.; Tolliver, Kyla M.; Haddad, Nadine G.; Molleston, Jean P.; Pediatrics, School of MedicineIntroduction: Glycogenic hepatopathy (GH) is a rare complication of type I diabetes mellitus (DM1), resulting in abnormal deposition of glycogen in the liver due to poor glycemic control. Clinical characteristics and natural history of GH are not completely understood in children. In this study, we investigated clinical, biochemical, histologic parameters and outcomes in children with GH. Method: This was a retrospective review of patients less than 18 years old diagnosed with GH and DM. GH was confirmed on liver biopsy. Medical records were reviewed for clinical presentation, laboratory tests, and clinical outcomes. Liver biopsy findings were reviewed by a pediatric pathologist (I. A. G.). Results: Nine children were diagnosed with GH and type 1 DM. The median age at diagnosis of GH was 16 (IQR 14.5-17) years. Duration of diagnosis of DM until GH diagnosis was 7 (IQR 5-11) years. The median frequency of diabetic ketoacidosis before GH diagnosis was three times (IQR 2-5.25). Peak Aspartate transaminase (AST) and Alanine transaminase (ALT) ranged from 115 to 797, and 83-389 units/L, respectively. Only two children had mild fibrosis. Seven of nine had steatosis without steatohepatitis. There was no correlation between glycosylated hemoglobin (HbA1c), or other laboratory tests and liver fibrosis on biopsy. HbA1c was 11.2 (IQR 10.2-12.8) at GH diagnosis and 9.8 (IQR 9.5-10.8) with normalization of liver enzymes. Conclusion: GH appears to be related to poor glycemic control in teenagers with long-term diabetes. GH presents with high to very high aminotransferase especially AST > ALT and resolves with modestly improved glycemic control. Diffuse hepatocyte swelling, steatosis, minimal fibrosis without hepatocyte ballooning or lobular inflammation are most common histological features.Item Clinical Trials in Pancreatitis: Opportunities and Challenges in the Design and Conduct of Patient-Focused Clinical Trials in Recurrent Acute and Chronic Pancreatitis: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop(Wolters Kluwer, 2022) Hart, Phil A.; Andersen, Dana K.; Lyons, Erica; Cote, Gregory A.; Cruz-Monserrate, Zobeida; Dworkin, Robert H.; Elmunzer, B. Joseph; Fogel, Evan L.; Forsmark, Christopher E.; Gilron, Ian; Golden, Megan; Gozu, Aysegul; McNair, Lindsay; Pandol, Stephen J.; Perito, Emily R.; Evans Phillips, Anna; Rabbitts, Jennifer A.; Whitcomb, David C.; Windsor, John A.; Yadav, Dhiraj; Palermo, Tonya M.; Medicine, School of MedicineRecurrent acute pancreatitis and chronic pancreatitis represent high morbidity diseases, which are frequently associated with chronic abdominal pain, pancreatic insufficiencies, and reduced quality of life. Currently, there are no therapies to reverse or delay disease progression, and clinical trials are needed to investigate potential interventions that would address this important gap. This conference report provides details regarding information shared during a National Institute of Diabetes and Digestive and Kidney Diseases-sponsored workshop on Clinical Trials in Pancreatitis that sought to clearly delineate the current gaps and opportunities related to the design and conduct of patient-focused trials in recurrent acute pancreatitis and chronic pancreatitis. Key stakeholders including representatives from patient advocacy organizations, physician investigators (including clinical trialists), the US Food and Drug Administration, and the National Institutes of Health convened to discuss challenges and opportunities with particular emphasis on lessons learned from trials in participants with other painful conditions, as well as the value of incorporating the patient perspective throughout all stages of trials.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.