Increased systemic Th17 cytokines are associated with diastolic dysfunction in children and adolescents with diabetic ketoacidosis.
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SUBMITTER: Hoffman WH
PROVIDER: S-EPMC3754936 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ObjectivesTo examine the temporal patterns of hospitalizations with diabetic ketoacidosis (DKA) in the pediatric population and their associated fiscal impact.MethodsThe Texas Inpatient Public Use Data File was used to identify hospitalizations of state residents aged 1month-19 years with a primary diagnosis of DKA during 2005-2014. Temporal changes of population-adjusted hospitalization rates and hospitalization volumes were examined for the whole cohort and on stratified analyses of sociodemographic attributes. Changes in the aggregate and per-hospitalization charges were assessed overall and on stratified analyses.ResultsThere were 24,072 DKA hospitalizations during the study period. The population-adjusted hospitalization rate for the whole cohort increased from 31.3 to 35.9 per 100,000 between 2005-2006 and 2013-2014. Hospitalization volume increased by 30.2% over the same period, driven mainly by males, ethnic minorities, those with Medicaid insurance and uninsured patients. The aggregate hospital charges increased from approximately $69 million to $130 million between 2005-2006 and 2013-2014, with 66% of the rise being due to increased per-hospitalization charges.ConclusionsThere was progressive rise in pediatric DKA hospitalizations over the last decade, with concurrent near-doubling of the associated fiscal footprint. Marked disparities were noted in the increasing hospitalization burden of DKA, born predominantly by racial and ethnic minorities, as well as by the underinsured and the uninsured. Further studies are needed to identify scalable preventive measures to achieve an equitable reduction of pediatric DKA events.
| S-EPMC7790255 | biostudies-literature
Project description:ObjectivesTo characterize hemodynamic alterations occurring during diabetic ketoacidosis (DKA) in a large cohort of children and to identify clinical and biochemical factors associated with hypertension.Study designThis was a planned secondary analysis of data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in DKA Study, a randomized clinical trial of fluid resuscitation protocols for children in DKA. Hemodynamic data (heart rate, blood pressure) from children with DKA were assessed in comparison with normal values for age and sex. Multivariable statistical modeling was used to explore clinical and laboratory predictors of hypertension.ResultsAmong 1258 DKA episodes, hypertension was documented at presentation in 154 (12.2%) and developed during DKA treatment in an additional 196 (15.6%), resulting in a total of 350 DKA episodes (27.8%) in which hypertension occurred at some time. Factors associated with hypertension at presentation included more severe acidosis, (lower pH and lower pCO2), and stage 2 or 3 acute kidney injury. More severe acidosis and lower Glasgow Coma Scale scores were associated with hypertension occurring at any time during DKA treatment.ConclusionsDespite dehydration, hypertension occurs in a substantial number of children with DKA. Factors associated with hypertension include greater severity of acidosis, lower pCO2, and lower Glasgow Coma Scale scores during DKA treatment, suggesting that hypertension might be centrally mediated.
| S-EPMC7414786 | biostudies-literature
Project description:Childhood obesity continues to escalate worldwide and may affect left ventricular (LV) geometry and function. The aim of this study was to investigate the impact of obesity on prevalence of left ventricular hypertrophy (LVH) and diastolic dysfunction in children. In this analysis of prospectively collected cross-sectional data of children between 5 and 16 years of age from randomly selected schools in Peru, parameters of LV geometry and function were compared according to presence or absence of obesity (body mass index z-score > 2). LVH was based on left ventricular mass index (LVMI) adjusted for age and sex and defined by a z-score of > 2. LV diastolic function was assessed using mitral inflow early-to-late diastolic flow (E/A) ratio, peak early diastolic tissue velocities of the lateral mitral annulus (E'), early diastolic transmitral flow velocity to tissue Doppler mitral annular early diastolic velocity (E/E') ratio, and left atrial volume index (LAVI). Among 1023 children, 681 children (mean age 12.2 ± 3.1 years, 341 male (50.1%)) were available for the present analysis, of which 150 (22.0%) were obese. LVH was found in 21 (14.0%) obese and in 19 (3.6%) non-obese children (padjusted < 0.001). LVMI was greater in obese than that in non-obese children (36.1 ± 8.6 versus 28.7 ± 6.9 g/m2.7, p < 0.001). The mean mitral E/E' ratio and LAVI were significantly higher in obese than those in non-obese individuals (E/E': 5.2 ± 1.1 versus 4.9 ± 0.8, padjusted = 0.043; LAVI 11.0 ± 3.2 versus 9.6 ± 2.9, padjusted = 0.001), whereas E' and E/A ratio were comparable. Childhood obesity was associated with left ventricular hypertrophy and determinants of diastolic dysfunction.ClinicalTrials.gov Identifier: NCT02353663.
| S-EPMC8219764 | biostudies-literature
Project description:The objective of this study was to evaluate the effectiveness of a brief, office-based educational intervention to increase parent or patient recognition of the early warning signs and symptoms of diabetic ketoacidosis (DKA). Forty-two patients aged > 13 years and 34 parents of children aged ≤ 13 years were given a pretest questionnaire about their knowledge of signs and symptoms of DKA and sick day management practices. They received a brief refresher course on sick day management specific to their treatment modality (pump vs. injection) and were given a take-home flow sheet of guidelines for diabetes sick day management. Subjects were retested with the same knowledge questionnaire after 6 to 12 months. Patients or parents scored higher on the posttest than the pretest and called the emergency line for assistance more frequently (p = .032) following the intervention. Emergency department visits were significantly reduced in adolescents (p = .024). A short educational intervention and printed management tool is effective in improving sick day and DKA knowledge and appears to be effective in reducing emergency department visits by increasing utilization of a diabetes emergency line for early outpatient intervention.
| S-EPMC7774356 | biostudies-literature
Project description:BackgroundDiabetes is a leading cause of mortality and morbidity across the world. Over 50% of deaths among diabetic patients are caused by cardiovascular diseases. Cardiac diastolic dysfunction is one of the key early signs of diabetic cardiomyopathy, which often occurs before systolic dysfunction. However, no drug is currently licensed for its treatment.MethodsType 9 adeno-associated virus combined with cardiac Troponin T promoter were employed to manipulate miR-21 expression in the leptin receptor-deficient (db/db) mice. Cardiac structure and functions were measured by echocardiography and hemodynamic examinations. Primary cardiomyocytes and cardiomyocyte cell lines were used to perform gain/loss-of-function assays in vitro.ResultsWe observed a significant reduction of miR-21 in the diastolic dysfunctional heart of db/db mice. Remarkably, delivery of miR-21 efficiently protected against the early impairment in cardiac diastolic dysfunction, represented by decreased ROS production, increased bioavailable NO and relieved diabetes-induced cardiomyocyte hypertrophy in db/db mice. Through bioinformatic analysis and Ago2 co-immunoprecipitation, we identified that miR-21 directly targeted gelsolin, a member of the actin-binding proteins, which acted as a transcriptional cofactor in signal transduction. Moreover, down-regulation of gelsolin by siRNA also attenuated the early phase of diabetic cardiomyopathy.ConclusionOur findings reveal a new role of miR-21 in attenuating diabetic cardiomyopathy by targeting gelsolin, and provide a molecular basis for developing a miRNA-based therapy against diabetic cardiomyopathy.
| S-EPMC6122727 | biostudies-literature
Project description:Diabetic cardiomyopathy (DCM) is one of the most essential cardiovascular complications in diabetic patients associated with glucose and lipid metabolism disorder, fibrosis, oxidative stress, and inflammation in cardiomyocytes. Despite increasing research on the molecular pathogenesis of DCM, it is still unclear whether metabolic pathways and alterations are probably involved in the development of DCM. This study aims to characterize the metabolites of DCM and to identify the relationship between metabolites and their biological processes or biological states through untargeted metabolic profiling. UPLC-MS/MS was applied to profile plasma metabolites from 78 patients with diabetes (39 diabetes with DCM and 39 diabetes without DCM as controls). A total of 2,806 biochemical were detected. Compared to those of DM patients, 78 differential metabolites in the positive-ion mode were identified in DCM patients, including 33 up-regulated and 45 down-regulated metabolites; however, there were only six differential metabolites identified in the negative mode including four up-regulated and two down-regulated metabolites. Alterations of several serum metabolites, including lipids and lipid-like molecules, organic acids and derivatives, organic oxygen compounds, benzenoids, phenylpropanoids and polyketides, and organoheterocyclic compounds, were associated with the development of DCM. KEGG enrichment analysis showed that there were three signaling pathways (metabolic pathways, porphyrin, chlorophyll metabolism, and lysine degradation) that were changed in both negative- and positive-ion modes. Our results demonstrated that differential metabolites and lipids have specific effects on DCM. These results expanded our understanding of the metabolic characteristics of DCM and may provide a clue in the future investigation of reducing the incidence of DCM. Furthermore, the metabolites identified here may provide clues for clinical management and the development of effective drugs.
| S-EPMC9150260 | biostudies-literature
Project description:Cardiac fibroblast (CF) proliferation and activation play important roles in cardiac fibrosis and diastolic dysfunction (DD), which are involved in fibrosis-associated cardiovascular diseases. A previous study showed that ivabradine, a specific heart rate (HR)-lowering agent, significantly ameliorated DD in diabetic db/db mice by reducing HR. Herein, we attempted to determine whether ivabradine has antifibrotic and cardioprotective effects in diabetic mice by directly suppressing CF proliferation and activation, independent of a reduction in HR. We found that knockdown of c-Jun N-terminal kinase (JNK) or p38 mitogen-activated protein kinase (MAPK), or treatment with ivabradine, reduced JNK and p38 MAPK phosphorylation and the protein expression of proliferating cell nuclear antigen, collagen I, collagen III, tissue inhibitor of matrix metalloproteinase 2, and α-smooth muscle actin, accompanied with upregulation of matrix metalloproteinase 2 both in high glucose-treated neonatal rat CFs and left ventricular CFs isolated from db/db mice. However, zatebradine (a HR-lowering agent) did not have these effects in vitro or in vivo. In addition, cardiac fibrosis and DD were ameliorated in db/db mice that were intravenously administered lentiviruses carrying short hairpin RNAs targeting JNK and p38 MAPK or administered ivabradine. Taken together, these findings demonstrate that the ivabradine-induced amelioration of cardiac fibrosis, and DD in db/db mice may be at least in part attributable to the suppression of CF proliferation and activation, through the inhibition of JNK and p38 MAPK.
| S-EPMC8259788 | biostudies-literature
Project description:ObjectivePrevious studies show that vasogenic cerebral edema (CE) occurs during diabetic ketoacidosis (DKA) treatment in children, but the role of intravenous fluids in contributing to CE is unclear. We used magnetic resonance diffusion weighted imaging to quantify subclinical CE in children with DKA randomized to 2 intravenous fluid regimens.MethodsChildren with DKA were randomized to receive fluids at a more rapid rate (n = 8) or a slower rate (n = 10), with all other aspects of DKA treatment kept identical. Children underwent diffusion weighted imaging 3 to 6 hours and 9 to 12 hours after beginning DKA treatment and after recovery from DKA (≥ 72 hours after beginning treatment). We calculated brain apparent diffusion coefficient (ADC) values as the average of measurements in the basal ganglia, thalamus, frontal white matter, and hippocampus and determined the mean brain ADC value during DKA treatment by averaging data from the 3- to 6-hour and 9- to 12-hour measurements. The difference in mean brain ADC between DKA treatment and postrecovery was used as an index of the severity of CE during DKA treatment.ResultsMean brain ADC values during DKA treatment were significantly higher than postrecovery values, consistent with vasogenic CE (842 ± 38 vs 800 ± 41 × 10(-6) mm(2)/second, P = .002). We did not detect significant differences in ADC elevation in children treated with more rapid versus slower rehydration (β coefficient 0.11 for 1 SD change in ADC, 95% confidence interval: -0.91 to 1.13).ConclusionsADC changes during DKA treatment (reflective of vasogenic CE) do not appear to be substantially affected by the rate of intravenous fluid administration.
| S-EPMC3529948 | biostudies-literature
Project description:Alpelisib is a phosphoinositol-3-kinase alpha catalytic subunit (PIK3CA) inhibitor used in patients with PIK3CA mutated breast cancer. The phosphatidylinositol 3-kinase (PI3K) pathway is responsible for activating protein kinase-B (AKT), and activated AKT promotes translation of glucose transporter 4 and glycogen synthesis in insulin-responsive tissues. Therefore, it is perhaps not surprising that hyperglycemia is the most common side effect of alpelisib, though diabetic ketoacidosis (DKA) appears to be a rare complication. This case describes the unique presentation of a patient with no prior history of diabetes who presented with DKA after starting alpelisib, and returned to euglycemia off of insulin just three days after stopping the drug suggesting that alpelisib can cause DKA in patients who did not previously have diabetes, and that the hyperglycemia is completely reversible upon discontinuation of the PIK3CA inhibitor and consequent restoration of the PI3K/AKT pathway.
| S-EPMC8648282 | biostudies-literature
Project description:Background/objectiveThe prevalence of diabetic ketoacidosis (DKA) in gestational diabetes mellitus (GDM) is very low. We describe a patient with GDM in whom severe DKA with intrauterine fetal demise developed in the setting of nonadherence to therapy.Case reportA 33-year-old woman, G2P0010, with no preexisting diabetes mellitus (DM) presented at 30 weeks of gestation with acute-onset altered sensorium, nausea, and emesis. GDM was diagnosed at 15 weeks of gestation with a serum glucose level of 266 mg/dL (70-134 mg/dL) after 1-hour 50-gram glucose challenge test. Glycated hemoglobin (HbA1C) was 5.9% (41 mmol/mol) at the time of GMD diagnosis. Insulin was initiated at week 20 of gestation. On presentation, serum glucose level of 920 mg/dL (70-110 mg/dL), pH of 7.02 (7.32-7.43), anion gap level of 38 mmol (5-17 mmol), bicarbonate level of 5.0 mEq/L (22-29 mEq/L), and large serum ketones were found. Ultrasound showed intrauterine fetal demise. She received intravenous fluids and continuous insulin. Following the spontaneous delivery of a nonviable fetus, DKA was resolved. Negative antiglutamic acid decarboxylase, islet cell, and zinc transporter 8 antibodies, C-peptide level of 2.4 ng/dL (1.1-4.4 ng/dL), and HbA1C level of 9% (75 mmol/mol) were found. Inpatient management included basal-bolus and sliding scale insulin therapies. Metformin was added upon discharge 7 days after admission. The HbA1C levels were 5.3% (34 mmol/mol) and 5% (31 mmol/mol) at the 3- and 6-month follow-ups, respectively. Insulin was discontinued. Currently, the patient is on metformin and glucagon-like peptide 1 receptor agonist.DiscussionThe development of insulin resistance during pregnancy is driven by multiple factors. Approximately 1% to 2% of pregnant women with impaired glucose tolerance develop DKA; most cases occur in women with type 1 DM. The approximate incidence of DKA in GDM is 0.02%.ConclusionDKA complicating GDM is extremely infrequent, but it cannot be dismissed. Early recognition along with prompt and appropriate medical and obstetrical management is critical.
| S-EPMC9508574 | biostudies-literature