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Incidence of Laryngotracheal Stenosis after Thermal Inhalation Airway Injury.
Lowery AS, Dion G, Thompson C, Weavind L, Shinn J, McGrane S, Summitt B, Gelbard A
(2019) J Burn Care Res 40: 961-965
MeSH Terms: Burns, Inhalation, Cohort Studies, Female, Humans, Hyperglycemia, Injury Severity Score, Intensive Care Units, Intubation, Intratracheal, Laryngostenosis, Leukocytosis, Male, Middle Aged, Respiration, Artificial, Retrospective Studies, Time Factors, Tracheal Stenosis, Tracheostomy
Show Abstract · Added July 30, 2020
Inhalation injury is independently associated with burn mortality, yet little information is available on the incidence, risk factors, or functional outcomes of thermal injury to the airway. In patients with thermal inhalation injury, we sought to define the incidence of laryngotracheal stenosis (LTS), delineate risk factors associated with LTS development, and assess long-term tracheostomy dependence as a proxy for laryngeal function. Retrospective cohort study of adult patients treated for thermal inhalation injury at a single institution burn critical care unit from 2012 to 2017. Eligible patients' records were assessed for LTS (laryngeal, subglottic, or tracheal stenosis). Patient characteristics, burn injury characteristics, and treatment-specific covariates were assessed. Descriptive statistics, Mann-Whitney U-tests, odds ratio, and chi-square tests compared LTS versus non-LTS groups. Of 129 patients with thermal inhalation injury during the study period, 8 (6.2%) developed LTS. When compared with the non-LTS group, patients with LTS had greater mean TBSA (mean 30.3, Interquartile Range 7-57.5 vs 10.5, Interquartile Range 0-15.12, P = .01), higher grade of inhalation injury (mean 2.63 vs 1.80, P = .05), longer duration of intubation (12.63 vs 5.44; P < .001), and greater inflammatory response (mean white blood cell count on presentation 25.8 vs 14.9, P = .02, mean hyperglycemia on presentation 176.4 vs 136.9, P = .01). LTS patients had a significantly higher rate of tracheostomy dependence at last follow-up (50 vs 1.7%, P < .001). Six percent of patients with thermal inhalation injury develop LTS. LTS was associated with more severe thermal airway injury, longer duration of intubation, and more severe initial host inflammation. Patients with inhalation injury and LTS are at high risk for tracheostomy dependence. In burn patients with thermal inhalation injury, laryngeal evaluation and directed therapy should be incorporated early into multispecialty pathways of care.
© American Burn Association 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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17 MeSH Terms
Iatrogenic Hyperinsulinemia, Not Hyperglycemia, Drives Insulin Resistance in Type 1 Diabetes as Revealed by Comparison With GCK-MODY (MODY2).
Gregory JM, Smith TJ, Slaughter JC, Mason HR, Hughey CC, Smith MS, Kandasamy B, Greeley SAW, Philipson LH, Naylor RN, Letourneau LR, Abumrad NN, Cherrington AD, Moore DJ
(2019) Diabetes 68: 1565-1576
MeSH Terms: Adolescent, Adult, Diabetes Mellitus, Type 2, Female, Humans, Hyperglycemia, Hyperinsulinism, Insulin Resistance, Male, Middle Aged, Models, Theoretical, Young Adult
Show Abstract · Added May 17, 2019
Although insulin resistance consistently occurs with type 1 diabetes, its predominant driver is uncertain. We therefore determined the relative contributions of hyperglycemia and iatrogenic hyperinsulinemia to insulin resistance using hyperinsulinemic-euglycemic clamps in three participant groups ( = 10/group) with differing insulinemia and glycemia: healthy control subjects (euinsulinemia and euglycemia), glucokinase-maturity-onset diabetes of the young (GCK-MODY; euinsulinemia and hyperglycemia), and type 1 diabetes (hyperinsulinemia and hyperglycemia matching GCK-MODY). We assessed the contribution of hyperglycemia by comparing insulin sensitivity in control and GCK-MODY and the contribution of hyperinsulinemia by comparing GCK-MODY and type 1 diabetes. Hemoglobin A was normal in control subjects and similarly elevated for type 1 diabetes and GCK-MODY. Basal insulin levels in control subjects and GCK-MODY were nearly equal but were 2.5-fold higher in type 1 diabetes. Low-dose insulin infusion suppressed endogenous glucose production similarly in all groups and suppressed nonesterified fatty acids similarly between control subjects and GCK-MODY, but to a lesser extent for type 1 diabetes. High-dose insulin infusion stimulated glucose disposal similarly in control subjects and GCK-MODY but was 29% and 22% less effective in type 1 diabetes, respectively. Multivariable linear regression showed that insulinemia-but not glycemia-was significantly associated with muscle insulin sensitivity. These data suggest that iatrogenic hyperinsulinemia predominates in driving insulin resistance in type 1 diabetes.
© 2019 by the American Diabetes Association.
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12 MeSH Terms
B lymphocytes protect islet β cells in diabetes prone NOD mice treated with imatinib.
Wilson CS, Spaeth JM, Karp J, Stocks BT, Hoopes EM, Stein RW, Moore DJ
(2019) JCI Insight 5:
MeSH Terms: Animals, Autoimmunity, B-Lymphocytes, Cell Proliferation, Diabetes Mellitus, Type 1, Disease Models, Animal, Homeodomain Proteins, Hyperglycemia, Imatinib Mesylate, Insulin, Insulin-Secreting Cells, Islets of Langerhans, Maf Transcription Factors, Large, Mice, Mice, Inbred C57BL, Mice, Inbred NOD, Mice, Knockout
Show Abstract · Added April 10, 2019
Imatinib (Gleevec) reverses type 1 diabetes (T1D) in NOD mice and is currently in clinical trials in individuals with recent-onset disease. While research has demonstrated that imatinib protects islet β cells from the harmful effects of ER stress, the role the immune system plays in its reversal of T1D has been less well understood, and specific cellular immune targets have not been identified. In this study, we demonstrate that B lymphocytes, an immune subset that normally drives diabetes pathology, are unexpectedly required for reversal of hyperglycemia in NOD mice treated with imatinib. In the presence of B lymphocytes, reversal was linked to an increase in serum insulin concentration, but not an increase in islet β cell mass or proliferation. However, improved β cell function was reflected by a partial recovery of MafA transcription factor expression, a sensitive marker of islet β cell stress that is important to adult β cell function. Imatinib treatment was found to increase the antioxidant capacity of B lymphocytes, improving reactive oxygen species (ROS) handling in NOD islets. This study reveals a novel mechanism through which imatinib enables B lymphocytes to orchestrate functional recovery of T1D β cells.
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17 MeSH Terms
Rapid changes in the microvascular circulation of skeletal muscle impair insulin delivery during sepsis.
Mignemi NA, McClatchey PM, Kilchrist KV, Williams IM, Millis BA, Syring KE, Duvall CL, Wasserman DH, McGuinness OP
(2019) Am J Physiol Endocrinol Metab 316: E1012-E1023
MeSH Terms: Animals, Capillaries, Capillary Permeability, Disease Models, Animal, Echocardiography, Hyperglycemia, Insulin, Insulin Resistance, Lipopolysaccharides, Mice, Microcirculation, Microvessels, Muscle Fibers, Skeletal, Muscle, Skeletal, Sepsis
Show Abstract · Added March 26, 2019
Sepsis costs the healthcare system $23 billion annually and has a mortality rate between 10 and 40%. An early indication of sepsis is the onset of hyperglycemia, which is the result of sepsis-induced insulin resistance in skeletal muscle. Previous investigations have focused on events in the myocyte (e.g., insulin signaling and glucose transport and subsequent metabolism) as the causes for this insulin-resistant state. However, the delivery of insulin to the skeletal muscle is also an important determinant of insulin action. Skeletal muscle microvascular blood flow, which delivers the insulin to the muscle, is known to be decreased during sepsis. Here we test whether the reduced capillary blood flow to skeletal muscle belies the sepsis-induced insulin resistance by reducing insulin delivery to the myocyte. We hypothesize that decreased capillary flow and consequent decrease in insulin delivery is an early event that precedes gross cardiovascular alterations seen with sepsis. This hypothesis was examined in mice treated with either lipopolysaccharide (LPS) or polymicrobial sepsis followed by intravital microscopy of the skeletal muscle microcirculation. We calculated insulin delivery to the myocyte using two independent methods and found that LPS and sepsis rapidly reduce insulin delivery to the skeletal muscle by ~50%; this was driven by decreases in capillary flow velocity and the number of perfused capillaries. Furthermore, the changes in skeletal muscle microcirculation occur before changes in both cardiac output and arterial blood pressure. These data suggest that a rapid reduction in skeletal muscle insulin delivery contributes to the induction of insulin resistance during sepsis.
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15 MeSH Terms
Factors Associated With Insulin Resistance in Adults With HIV Receiving Contemporary Antiretroviral Therapy: a Brief Update.
Hulgan T
(2018) Curr HIV/AIDS Rep 15: 223-232
MeSH Terms: Adult, Anti-HIV Agents, HIV, HIV Infections, HIV Integrase Inhibitors, HIV Protease Inhibitors, Humans, Hyperglycemia, Inflammation, Insulin Resistance, Mitochondria, Obesity
Show Abstract · Added December 11, 2019
PURPOSE OF REVIEW - This narrative review summarizes recent data on factors associated with insulin resistance (IR) in adults with HIV, including contemporary antiretroviral therapy (ART).
RECENT FINDINGS - IR remains common in persons with HIV, even those receiving contemporary ART. Generalized and abdominal obesity and ectopic fat are correlates of IR, and emerging data have identified associations with biomarkers of inflammation and immune activation. Small studies suggest associations between mitochondria and IR. In ART-naïve individuals, IR increased within 4 weeks of starting ART in persons receiving contemporary boosted protease inhibitors or an integrase inhibitor. The importance of IR in non-diabetic persons with HIV will continue to grow as the population ages and obesity increases. Non-invasive estimates of IR appear to perform well in persons with HIV, but clinically relevant cutoffs are uncertain. Unexpected metabolic effects of newer HIV integrase inhibitors have been reported; thus, careful observation for and studies of IR are still warranted.
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The Vasculature in Prediabetes.
Wasserman DH, Wang TJ, Brown NJ
(2018) Circ Res 122: 1135-1150
MeSH Terms: Angiotensin-Converting Enzyme Inhibitors, Animals, Blood Vessels, Cardiovascular Diseases, Combined Modality Therapy, Diabetes Mellitus, Type 2, Diet, Reducing, Disease Progression, Endothelium, Vascular, Extracellular Matrix, Fatty Acids, Nonesterified, Fibrinolysis, Glucose, Humans, Hyperglycemia, Hypoglycemic Agents, Inflammation, Insulin Resistance, Life Style, Metabolic Syndrome, Mice, MicroRNAs, Microcirculation, Muscle, Skeletal, Obesity, Prediabetic State, Risk, Weight Loss
Show Abstract · Added March 26, 2019
The frequency of prediabetes is increasing as the prevalence of obesity rises worldwide. In prediabetes, hyperglycemia, insulin resistance, and inflammation and metabolic derangements associated with concomitant obesity cause endothelial vasodilator and fibrinolytic dysfunction, leading to increased risk of cardiovascular and renal disease. Importantly, the microvasculature affects insulin sensitivity by affecting the delivery of insulin and glucose to skeletal muscle; thus, endothelial dysfunction and extracellular matrix remodeling promote the progression from prediabetes to diabetes mellitus. Weight loss is the mainstay of treatment in prediabetes, but therapies that improved endothelial function and vasodilation may not only prevent cardiovascular disease but also slow progression to diabetes mellitus.
© 2018 American Heart Association, Inc.
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28 MeSH Terms
Measures of Adherence and Challenges in Using Glucometer Data in Youth with Type 1 Diabetes: Rethinking the Value of Self-Report.
Datye KA, Patel NJ, Jaser SS
(2017) J Diabetes Res 2017: 1075428
MeSH Terms: Adolescent, Adolescent Behavior, Blood Glucose, Blood Glucose Self-Monitoring, Caregivers, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Female, Glycated Hemoglobin A, Humans, Hyperglycemia, Hypoglycemia, Hypoglycemic Agents, Insulin, Insulin Infusion Systems, Male, Patient Compliance, Self Report, Self-Management, Tennessee
Show Abstract · Added May 18, 2018
Purpose - The current study compares the relative strength of associations of different adherence measures with glycemic control in adolescents with type 1 diabetes, while highlighting the challenges in using more objective measures (i.e., glucometer data).
Methods - Adolescents with type 1 diabetes ( = 149) and their caregivers completed a questionnaire measure assessing adolescents' adherence (Self-Care Inventory (SCI)) to the diabetes regimen. Adolescents' glucometers were downloaded to determine average blood glucose checks per day, as an objective measure of adherence. A measure of glycemic control (hemoglobin A1c (HbA1c)) was obtained as part of adolescents' regular clinic visits.
Results - Adolescents' self-reported adherence to the treatment regimen was more strongly correlated with HbA1c than caregivers' reports of adherence. In multivariate analyses, both adolescents' self-report of adherence and average blood glucose checks per day (obtained via a glucometer) were significant predictors of HbA1c. Challenges to obtaining glucometer data were identified.
Conclusions - The findings highlight adolescents' self-report of adherence using the SCI as a brief and meaningful measure to understand and improve adolescents' glycemic control, particularly when glucometer data is difficult to obtain.
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20 MeSH Terms
Sleep in Type 1 Diabetes: Implications for Glycemic Control and Diabetes Management.
Perez KM, Hamburger ER, Lyttle M, Williams R, Bergner E, Kahanda S, Cobry E, Jaser SS
(2018) Curr Diab Rep 18: 5
MeSH Terms: Diabetes Mellitus, Type 1, Humans, Hyperglycemia, Patient Compliance, Sleep, Sleep Wake Disorders, Treatment Outcome
Show Abstract · Added May 15, 2018
PURPOSE OF REVIEW - To highlight recent findings from studies of sleep in type 1 diabetes (T1D), with a focus on the role of sleep in self-management, the cognitive and psychosocial outcomes related to sleep disturbances, and factors associated with sleep disturbances specific to T1D.
RECENT FINDINGS - People with T1D experience higher rates of sleep disturbances than people without diabetes, and these disturbances have negative implications for glycemic control and diabetes management, as well as psychosocial and cognitive outcomes. Inconsistent sleep timing (bedtime and wake time) has emerged as a potential target for interventions, as variability in sleep timing has been linked with poorer glycemic control and adherence to treatment. Sleep-promoting interventions and new diabetes technology have the potential to improve sleep in people with T1D. Sleep is increasingly considered a critical factor in diabetes management, but more multi-method and longitudinal research is needed. We emphasize the importance of sufficient and consistent sleep for people with T1D, and the need for providers to routinely assess sleep among patients with T1D.
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7 MeSH Terms
Association of Blood Pressure, Blood Glucose, and Temperature With Neurological Outcome After Childhood Stroke.
Grelli KN, Gindville MC, Walker CH, Jordan LC
(2016) JAMA Neurol 73: 829-35
MeSH Terms: Adolescent, Blood Glucose, Blood Pressure, Body Temperature, Brain Infarction, Child, Child, Preschool, Cohort Studies, Female, Humans, Hyperglycemia, Hypertension, Infant, Infant, Newborn, Male, Nervous System Diseases, Stroke
Show Abstract · Added March 24, 2020
IMPORTANCE - To our knowledge, no evidence-based guidelines are available for the best medical management of blood pressure, blood glucose levels, and temperature in pediatric patients after arterial ischemic stroke.
OBJECTIVE - To determine the prevalence of abnormal blood pressure, blood glucose levels, and temperature in pediatric patients with acute arterial ischemic stroke and to explore any association between these measures and neurological outcome.
DESIGN, SETTING, AND PARTICIPANTS - We performed a retrospective review of children aged 29 days to 18 years with their first arterial ischemic stroke between January 2009 and December 2013 at a tertiary academic children's hospital. Ninety-eight children with stroke were identified by an International Classification of Diseases, Ninth Revision, code search and medical record review. Blood pressure, blood glucose, and temperature data were collected for 5 days after the stroke. Hypertension was defined as systolic blood pressure at or above the 95th percentile for age, sex, and height for 2 consecutive recordings and 2 consecutive days. Hypotension was defined as systolic and/or diastolic blood pressure below the fifth percentile for age, sex, and height for 2 consecutive recordings. Hyperglycemia was defined as a blood glucose level of 200 mg/dL or greater. Morbidity and mortality at 3 months were documented. Data analyses were performed from July 1, 2014, to December 31, 2015.
INTERVENTIONS OR EXPOSURES - Abnormal blood pressure, blood glucose levels, and fever in the setting of arterial ischemic stroke.
MAIN OUTCOMES AND MEASURES - The a priori outcome measure was poor clinical outcome, defined as a Pediatric Stroke Outcome Measure score of 1 or greater, which represents a moderate neurological deficit.
RESULTS - The median (interquartile range) age of the 98 children was 6.0 (0.6-14.3) years, and 58 (59.2%) were male. Hypertension was present in 64 (65.3%), hypotension in 67 (68.4%), hyperglycemia in 17 (18.1%), and fever in 37 (37.8%). The strongest association with poor neurological outcome was an infarct size of 4% or greater of brain volume (odds ratio, 5.6; 95% CI, 2.0-15.4; P = .001). Hyperglycemia was also independently associated with poor neurological outcome (odds ratio, 3.9; 95% CI, 1.2-12.4; P = .02). Hypertension and fever were not significantly associated with infarct size, poor outcome, or death. Hypertension was not documented in 24 of 87 surviving children (27.6%) at 3-month follow-up and was not associated with poor neurological outcome.
CONCLUSIONS AND RELEVANCE - Abnormalities of blood pressure, blood glucose levels, and temperature are prevalent in children with arterial ischemic stroke. Infarct volume and hyperglycemia were associated with poor neurological outcome but hypertension and fever were not. Prospective studies that systematically record blood pressure, blood glucose, and temperature data are required to further assess the associations between these potentially modifiable physiological parameters and pediatric stroke outcome.
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Central injection of fibroblast growth factor 1 induces sustained remission of diabetic hyperglycemia in rodents.
Scarlett JM, Rojas JM, Matsen ME, Kaiyala KJ, Stefanovski D, Bergman RN, Nguyen HT, Dorfman MD, Lantier L, Wasserman DH, Mirzadeh Z, Unterman TG, Morton GJ, Schwartz MW
(2016) Nat Med 22: 800-6
MeSH Terms: Adipose Tissue, Animals, Blood Glucose, Blotting, Western, Body Composition, Brain, Carbon Radioisotopes, Deoxyglucose, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Diet, High-Fat, Disease Models, Animal, Ependymoglial Cells, Fibroblast Growth Factor 1, Forkhead Box Protein O1, Glucose Tolerance Test, Heart, Heat-Shock Proteins, Hyperglycemia, Hypothalamus, Injections, Intraventricular, Liver, Male, Mice, Mice, Knockout, Mice, Obese, Molecular Chaperones, Muscle, Skeletal, Myocardium, Neoplasm Proteins, Proto-Oncogene Proteins c-fos, Rats, Rats, Zucker, Real-Time Polymerase Chain Reaction, Receptor, Insulin, Remission Induction
Show Abstract · Added May 16, 2019
Type 2 diabetes (T2D) is among the most common and costly disorders worldwide. The goal of current medical management for T2D is to transiently ameliorate hyperglycemia through daily dosing of one or more antidiabetic drugs. Hypoglycemia and weight gain are common side effects of therapy, and sustained disease remission is not obtainable with nonsurgical approaches. On the basis of the potent glucose-lowering response elicited by activation of brain fibroblast growth factor (FGF) receptors, we explored the antidiabetic efficacy of centrally administered FGF1, which, unlike other FGF peptides, activates all FGF receptor subtypes. We report that a single intracerebroventricular injection of FGF1 at a dose one-tenth of that needed for antidiabetic efficacy following peripheral injection induces sustained diabetes remission in both mouse and rat models of T2D. This antidiabetic effect is not secondary to weight loss, does not increase the risk of hypoglycemia, and involves a novel and incompletely understood mechanism for increasing glucose clearance from the bloodstream. We conclude that the brain has an inherent potential to induce diabetes remission and that brain FGF receptors are potential pharmacological targets for achieving this goal.
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36 MeSH Terms