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Diabetologia Jun 2024As a result of early loss of the glucagon response, adrenaline is the primary counter-regulatory hormone in type 1 diabetes. Diminished adrenaline responses to...
AIMS/HYPOTHESIS
As a result of early loss of the glucagon response, adrenaline is the primary counter-regulatory hormone in type 1 diabetes. Diminished adrenaline responses to hypoglycaemia due to counter-regulatory failure are common in type 1 diabetes, and are probably induced by exposure to recurrent hypoglycaemia, however, the metabolic effects of adrenaline have received less research attention, and also there is conflicting evidence regarding adrenaline sensitivity in type 1 diabetes. Thus, we aimed to investigate the metabolic response to adrenaline and explore whether it is modified by prior exposure to hypoglycaemia.
METHODS
Eighteen participants with type 1 diabetes and nine healthy participants underwent a three-step ascending adrenaline infusion during a hyperinsulinaemic-euglycaemic clamp. Continuous glucose monitoring data obtained during the week before the study day were used to assess the extent of hypoglycaemia exposure.
RESULTS
While glucose responses during the clamp were similar between people with type 1 diabetes and healthy participants, plasma concentrations of NEFAs and glycerol only increased in the group with type 1 diabetes (p<0.001). Metabolomics revealed an increase in the most common NEFAs (p<0.01). Other metabolic responses were generally similar between participants with type 1 diabetes and healthy participants. Exposure to hypoglycaemia was negatively associated with the NEFA response; however, this was not statistically significant.
CONCLUSIONS/INTERPRETATION
In conclusion, individuals with type 1 diabetes respond with increased lipolysis to adrenaline compared with healthy participants by mobilising the abundant NEFAs in plasma, whereas other metabolic responses were similar. This may suggest that the metabolic sensitivity to adrenaline is altered in a pathway-specific manner in type 1 diabetes.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05095259.
Topics: Adult; Female; Humans; Male; Young Adult; Blood Glucose; Diabetes Mellitus, Type 1; Epinephrine; Fatty Acids, Nonesterified; Glucagon; Glucose Clamp Technique; Glycerol; Hypoglycemia; Insulin; Case-Control Studies
PubMed: 38427076
DOI: 10.1007/s00125-024-06116-5 -
BMC Cardiovascular Disorders Feb 2024This study was aimed to identify the risk factors that influence the mortality risk in patients with acute aortic dissection (AAD) within one year after discharge, and...
Risk factors for one-year mortality following discharge in patients with acute aortic dissection: development and validation of a predictive model in a cross-sectional study.
PURPOSE
This study was aimed to identify the risk factors that influence the mortality risk in patients with acute aortic dissection (AAD) within one year after discharge, and aimed to construct a predictive model for assessing mortality risk.
METHODS
The study involved 320 adult patients obtained from the Medical Information Mart for Intensive Care (MIMIC) database. Logistic regression analysis was conducted to identify potential risk factors associated with mortality in AAD patients within one year after discharge and to develop a predictive model. The performance of the predictive model was assessed using the receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA). To further validate the findings, patient data from the First Affiliated Hospital of Guangxi Medical University (157 patients) were analyzed.
RESULTS
Univariate and multivariate logistic regression analyses revealed that gender, length of hospital stay, highest blood urea nitrogen (BUN_max), use of adrenaline, and use of amiodarone were significant risk factors for mortality within one year after discharge (p < 0.05). The constructed model exhibited a consistency index (C-index) and an area under the ROC curve of 0.738. The calibration curve and DCA demonstrated that these indicators had a good degree of agreement and utility. The external validation results of the model also indicated good predictability (AUC = 0.700, p < 0.05).
CONCLUSION
The personalized scoring prediction model constructed by gender, length of hospital stays, BUN_max levels, as well as the use of adrenaline and amiodarone, can effectively identify AAD patients with high mortality risk within one year after discharge.
Topics: Adult; Humans; Cross-Sectional Studies; Patient Discharge; China; Amiodarone; Aortic Dissection; Epinephrine; Risk Factors; Retrospective Studies
PubMed: 38424525
DOI: 10.1186/s12872-024-03766-6 -
The Journal of Allergy and Clinical... May 2024Because of its favorable safety, sublingual immunotherapy (SLIT) for food allergy has been proposed as an alternative treatment for those in whom oral immunotherapy...
BACKGROUND
Because of its favorable safety, sublingual immunotherapy (SLIT) for food allergy has been proposed as an alternative treatment for those in whom oral immunotherapy (OIT) is of higher risk-older children, adolescents, adults, and those with a history of severe reactions. Although safe, SLIT has been shown to be less effective than OIT.
OBJECTIVE
To describe the safety of multifood SLIT in pediatric patients aged 4 to 18 years and the effectiveness of bypassing OIT buildup with an initial phase of SLIT.
METHODS
Patients aged 4 to 18 years were offered (multi)food SLIT. Patients built up to 2 mg protein SLIT maintenance over the course of 3 to 5 visits under nurse supervision. After 1 to 2 years of daily SLIT maintenance, patients were offered a low-dose oral food challenge (OFC) (cumulative dose, 300 mg protein) with the goal of bypassing OIT buildup.
RESULTS
Between summer 2020 and winter 2023, 188 patients were enrolled in SLIT (median age, 11 years). Four patients (2.10%) received epinephrine during buildup and went to the emergency department, but none experienced grade 4 (severe) reaction. A subset of 20 patients had 50 low-dose OFCs to 300 mg protein and 35 (70%) OFCs were successful, thereby bypassing OIT buildup.
CONCLUSIONS
In combination with very favorable safety of SLIT, with no life-threatening reactions and few reactions requiring epinephrine, we propose that an initial phase of SLIT to bypass supervised OIT buildup be considered for children in whom OIT is considered to be of higher risk.
Topics: Humans; Child; Food Hypersensitivity; Child, Preschool; Adolescent; Sublingual Immunotherapy; Female; Male; Administration, Oral; Allergens; Treatment Outcome; Desensitization, Immunologic; Administration, Sublingual; Epinephrine
PubMed: 38423293
DOI: 10.1016/j.jaip.2024.02.024 -
Pharmacology Research & Perspectives Apr 2024Changes in vascular biomechanics leading to increase in arterial stiffness play a pivotal role in circulatory dysfunction. Our objectives were to examine sex-specific...
Changes in vascular biomechanics leading to increase in arterial stiffness play a pivotal role in circulatory dysfunction. Our objectives were to examine sex-specific pharmacological changes related to the biomechanics and any structural modifications in small resistance arteries of Dahl salt-sensitive male and female rats. The composite Young modulus (CYM) was determined using pressure myograph recordings, and immunohistochemistry was used for the evaluation of any structural changes in the third-order mesenteric arteries (n = 6). Animals on high-salt diet developed hypertension with significant elevation in central and peripheral blood pressures and pulse wave velocity compared to those on regular diet. There were no significant differences observed in the CYM between any of the groups (i.e., males and females) in vehicle-treated time-control studies. The presence of verapamil (0.3 μM) significantly reduced CYM in hypertensive males without changes within females compared to vehicle. This effect was abolished by phenylephrine (0.3 μM). BaCl (100 μM), ouabain (100 μM), and L-NAME (0.3 μM) combined significantly increased CYM in vessels from in normotensive males and females but not in hypertensive males compared to vehicle. The increase in CYM was abolished in the presence of phenylephrine. Sodium nitroprusside (0.3 μM), in the presence of phenylephrine, significantly reduced CYM in male normotensive versus hypertensive, with no differences within females. Significant differences were observed in immunohistochemical assessment of biomechanical markers of arterial stiffness between males and females. Our findings suggest sex possibly due to pressure differences to be responsible for adaptive changes in biomechanics, and varied pharmacological responses in hypertensive state.
Topics: Rats; Male; Female; Animals; Rats, Inbred Dahl; Biomechanical Phenomena; Pulse Wave Analysis; Hypertension; Arteries; Phenylephrine; Sodium Chloride
PubMed: 38421097
DOI: 10.1002/prp2.1180 -
International Journal of Molecular... Feb 2024Anserine, an imidazole dipeptide, is present in the muscles of birds and fish and has various bioactivities, such as anti-inflammatory and anti-fatigue effects. However,...
Anserine, an imidazole dipeptide, is present in the muscles of birds and fish and has various bioactivities, such as anti-inflammatory and anti-fatigue effects. However, the effect of anserine on the development of heart failure remains unknown. We cultured primary cardiomyocytes with 0.03 mM to 10 mM anserine and stimulated them with phenylephrine for 48 h. Anserine significantly suppressed the phenylephrine-induced increases in cardiomyocyte hypertrophy, ANF and BNP mRNA levels, and histone H3K9 acetylation. An in vitro histone acetyltransferase (HAT) assay showed that anserine directly suppressed p300-HAT activity with an IC of 1.87 mM. Subsequently, 8-week-old male C57BL/6J mice were subjected to transverse aortic constriction (TAC) and were randomly assigned to receive daily oral treatment with anserine-containing material, Marine Active (60 or 200 mg/kg anserine) or vehicle for 8 weeks. Echocardiography revealed that anserine 200 mg/kg significantly prevented the TAC-induced increase in left ventricular posterior wall thickness and the decrease in left ventricular fractional shortening. Moreover, anserine significantly suppressed the TAC-induced acetylation of histone H3K9. These results indicate that anserine suppresses TAC-induced systolic dysfunction, at least in part, by inhibiting p300-HAT activity. Anserine may be used as a pharmacological agent for human heart failure therapy.
Topics: Animals; Humans; Male; Mice; Acetylation; Anserine; Cardiomegaly; Cardiomyopathies; Enzyme Inhibitors; Heart Failure; Histones; Mice, Inbred C57BL; Myocytes, Cardiac; Phenylephrine; p300-CBP Transcription Factors
PubMed: 38397020
DOI: 10.3390/ijms25042344 -
Diabetes Care May 2024
Topics: Humans; Diabetes Mellitus, Type 1; Blood Glucose; Blood Glucose Self-Monitoring; Continuous Glucose Monitoring; Hypoglycemia; Epinephrine; Hypoglycemic Agents; Insulin
PubMed: 38394365
DOI: 10.2337/dc23-2501 -
Indian Journal of Ophthalmology Jul 2024To assess the effect of defocus incorporated multiple segments (DIMS) (Miyosmart) lenses on myopic progression in children not responding to low-concentration atropine...
To assess the effect of defocus incorporated multiple segments (DIMS) (Miyosmart) lenses on myopic progression in children not responding to low-concentration atropine (LCA) (0.01%) eye drops. A total of 10 children not responding to LCA (0.01%) eye drops were advised to start using the DIMS lens to halt the progression of myopia. The children were followed for a period of 1 year. Eight out of 10 children showed a reduction in the progression of myopia. Pre DIMS, the progression was -0.68 D ± 0.3 D sph, which reduced to -0.24 ± 0.2 diopter progression post DIMS lens in the eight children. The remaining two children still progressed by -0.57 ± 0.4 D sph over a year. The axial length growth reduced from 0.28 ± 0.3 mm to 0.16 ± 0.2 mm after using the DIMS lens in these non-responders. The DIMS lens shows initial promise in reducing the progression of myopia even in children not responding to LCA 0.01% eye drops.
Topics: Humans; Atropine; Child; Disease Progression; Ophthalmic Solutions; Mydriatics; Male; Refraction, Ocular; Female; Myopia; Eyeglasses; Follow-Up Studies; Adolescent; Dose-Response Relationship, Drug
PubMed: 38389263
DOI: 10.4103/IJO.IJO_2378_23 -
Acta Diabetologica May 2024The sympathetic nervous and hormonal counterregulatory responses to hypoglycaemia differ between people with type 1 and type 2 diabetes and may change along the course...
Counterregulatory hormone and symptom responses to hypoglycaemia in people with type 1 diabetes, insulin-treated type 2 diabetes or without diabetes: the Hypo-RESOLVE hypoglycaemic clamp study.
AIM
The sympathetic nervous and hormonal counterregulatory responses to hypoglycaemia differ between people with type 1 and type 2 diabetes and may change along the course of diabetes, but have not been directly compared. We aimed to compare counterregulatory hormone and symptom responses to hypoglycaemia between people with type 1 diabetes, insulin-treated type 2 diabetes and controls without diabetes, using a standardised hyperinsulinaemic-hypoglycaemic clamp.
MATERIALS
We included 47 people with type 1 diabetes, 15 with insulin-treated type 2 diabetes, and 32 controls without diabetes. Controls were matched according to age and sex to the people with type 1 diabetes or with type 2 diabetes. All participants underwent a hyperinsulinaemic-euglycaemic-(5.2 ± 0.4 mmol/L)-hypoglycaemic-(2.8 ± 0.13 mmol/L)-clamp.
RESULTS
The glucagon response was lower in people with type 1 diabetes (9.4 ± 0.8 pmol/L, 8.0 [7.0-10.0]) compared to type 2 diabetes (23.7 ± 3.7 pmol/L, 18.0 [12.0-28.0], p < 0.001) and controls (30.6 ± 4.7, 25.5 [17.8-35.8] pmol/L, p < 0.001). The adrenaline response was lower in type 1 diabetes (1.7 ± 0.2, 1.6 [1.3-5.2] nmol/L) compared to type 2 diabetes (3.4 ± 0.7, 2.6 [1.3-5.2] nmol/L, p = 0.001) and controls (2.7 ± 0.4, 2.8 [1.4-3.9] nmol/L, p = 0.012). Growth hormone was lower in people with type 2 diabetes than in type 1 diabetes, at baseline (3.4 ± 1.6 vs 7.7 ± 1.3 mU/L, p = 0.042) and during hypoglycaemia (24.7 ± 7.1 vs 62.4 ± 5.8 mU/L, p = 0.001). People with 1 diabetes had lower overall symptom responses than people with type 2 diabetes (45.3 ± 2.7 vs 58.7 ± 6.4, p = 0.018), driven by a lower neuroglycopenic score (27.4 ± 1.8 vs 36.7 ± 4.2, p = 0.012).
CONCLUSION
Acute counterregulatory hormone and symptom responses to experimental hypoglycaemia are lower in people with type 1 diabetes than in those with long-standing insulin-treated type 2 diabetes and controls.
Topics: Humans; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Male; Female; Hypoglycemia; Glucose Clamp Technique; Middle Aged; Adult; Insulin; Glucagon; Hypoglycemic Agents; Blood Glucose; Epinephrine; Aged; Case-Control Studies
PubMed: 38376580
DOI: 10.1007/s00592-024-02239-8 -
European Review For Medical and... Feb 2024Recent research suggests that butin may also exert neuroprotective effects. However, its influence on cognitive performance and, specifically, its potential to mitigate...
OBJECTIVE
Recent research suggests that butin may also exert neuroprotective effects. However, its influence on cognitive performance and, specifically, its potential to mitigate scopolamine-induced memory impairment remains unexplored. The aim of the study is to investigate the effects of butin on the cognitive and behavioral performance of rats with scopolamine-induced memory impairment.
MATERIALS AND METHODS
Scopolamine-injected memory-impediment model in rats was used to determine the efficacy of butin in higher and lower doses (10 and 20 mg/kg) for 14 days. Y-maze, along with Morris water, was used to assess the ability to recall spatial and working information. Biochemistry-related functions such as acetylcholinesterase, choline acetyltransferase, superoxide dismutase, glutathione transferase, malonaldehyde, catalase, nitric oxide, and neurotransmitters levels were estimated as indicators of free radical damage. Furthermore, we evaluated neuro-inflammatory responses by assessing tumor necrosis factor-alpha (TNF-α), interleukin 1 beta (IL-1β), interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF) and caspase-3 immuno-reactive proteins.
RESULTS
When assessed through behavioral paradigms, the butin-treated group enhanced the spatial and working memory of rodents. Scopolamine caused a substantial alteration in biochemical-related parameters, neuronal enzymatic, inflammation responses and apoptosis markers prominently restored by butin.
CONCLUSIONS
This study concludes that butin protects scopolamine-injected rats from behavioral impairments and neuronal damage by reducing apoptosis and neuroinflammation.
Topics: Animals; Rats; Acetylcholinesterase; Benzopyrans; Brain-Derived Neurotrophic Factor; Caspase 3; Hippocampus; Maze Learning; Memory Disorders; Oxidative Stress; Scopolamine
PubMed: 38375702
DOI: 10.26355/eurrev_202402_35334 -
JAMA Network Open Feb 2024While epinephrine and advanced airway management (AAM) (supraglottic airway insertion and endotracheal intubation) are commonly used for out-of-hospital cardiac arrest...
IMPORTANCE
While epinephrine and advanced airway management (AAM) (supraglottic airway insertion and endotracheal intubation) are commonly used for out-of-hospital cardiac arrest (OHCA), the optimal sequence of these interventions remains unclear.
OBJECTIVE
To evaluate the association of the sequence of epinephrine administration and AAM with patient outcomes after OHCA.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study analyzed the nationwide, population-based OHCA registry in Japan and included adults (aged ≥18 years) with OHCA for whom emergency medical services personnel administered epinephrine and/or placed an advanced airway between January 1, 2014, and December 31, 2019. The data analysis was performed between October 1, 2022, and May 12, 2023.
EXPOSURE
The sequence of intravenous epinephrine administration and AAM.
MAIN OUTCOMES AND MEASURES
The primary outcome was 1-month survival. Secondary outcomes were 1-month survival with favorable functional status and prehospital return of spontaneous circulation. To control imbalances in measured patient demographics, cardiac arrest characteristics, and bystander and prehospital interventions, propensity scores and inverse probability of treatment weighting (IPTW) were performed for shockable and nonshockable initial rhythm subcohorts.
RESULTS
Of 259 237 eligible patients (median [IQR] age, 79 [69-86] years), 152 289 (58.7%) were male. A total of 21 592 patients (8.3%) had an initial shockable rhythm, and 237 645 (91.7%) had an initial nonshockable rhythm. Using IPTW, all covariates between the epinephrine-first and AAM-first groups were well balanced, with all standardized mean differences less than 0.100. After IPTW, the epinephrine-first group had a higher likelihood of 1-month survival for both shockable (odds ratio [OR], 1.19; 95% CI, 1.09-1.30) and nonshockable (OR, 1.28; 95% CI, 1.19-1.37) rhythms compared with the AAM-first group. For the secondary outcomes, the epinephrine-first group experienced an increased likelihood of favorable functional status and prehospital return of spontaneous circulation for both shockable and nonshockable rhythms compared with the AAM-first group.
CONCLUSIONS AND RELEVANCE
These findings suggest that for patients with OHCA, administration of epinephrine before placement of an advanced airway may be the optimal treatment sequence for improved patient outcomes.
Topics: Adult; Humans; Male; Adolescent; Aged; Female; Out-of-Hospital Cardiac Arrest; Cohort Studies; Epinephrine; Intubation, Intratracheal; Odds Ratio
PubMed: 38372996
DOI: 10.1001/jamanetworkopen.2023.56863