The impact of hypoglycaemia awareness status on regional brain responses to acute hypoglycaemia in men with type 1 diabetes

Aims/hypothesis

Impaired awareness of hypoglycaemia (IAH) in type 1 diabetes increases the risk of severe hypoglycaemia sixfold and can be resistant to intervention. We explored the impact of IAH on central responses to hypoglycaemia to investigate the mechanisms underlying barriers to therapeutic intervention.

Methods

We conducted [¹⁵O]water positron emission tomography studies of regional brain perfusion during euglycaemia (target 5 mmol/l), hypoglycaemia (achieved level, 2.4 mmol/l) and recovery (target 5 mmol/l) in 17 men with type 1 diabetes: eight with IAH, and nine with intact hypoglycaemia awareness (HA).

Results

Hypoglycaemia with HA was associated with increased activation in brain regions including the thalamus, insula, globus pallidus (GP), anterior cingulate cortex (ACC), orbital cortex, dorsolateral frontal (DLF) cortex, angular gyrus and amygdala; deactivation occurred in the temporal and parahippocampal regions. IAH was associated with reduced catecholamine and symptom responses to hypoglycaemia vs HA (incremental AUC: autonomic scores, 26.2?±?35.5 vs 422.7?±?237.1; neuroglycopenic scores, 34.8?±?88.8 vs 478.9?±?311.1; both p?<?0.002). There were subtle differences (p?<?0.005, k?≥?50 voxels) in brain activation at hypoglycaemia, including early differences in the right central operculum, bilateral medial orbital (MO) cortex, and left posterior DLF cortex, with additional differences in the ACC, right GP and post- and pre-central gyri in established hypoglycaemia, and lack of deactivation in temporal regions in established hypoglycaemia.

Conclusions/interpretation

Differences in activation in the post- and pre-central gyri may be expected in people with reduced subjective responses to hypoglycaemia. Alterations in the activity of regions involved in the drive to eat (operculum), emotional salience (MO cortex), aversion (GP) and recall (temporal) suggest differences in the perceived importance and urgency of responses to hypoglycaemia in IAH compared with HA, which may be key to the persistence of the condition.

     

Mental Well‐Being Mediates the Relationship between Perceived Stress and Perceived Health

The association between stress and health has been well researched in the past; however, comparatively few mediators have been tested to understand the underlying mechanism. With increasing awareness on mental well‐being, this study evaluated the relationship between perceived stress and perceived health and examined mental well‐being as a mediator. Two‐hundred undergraduates aged 21 to 26 years completed the English Perceived Stress Scale, Health Status Questionnaire and Asian Mental Well‐Being Scale that assess perceived stress, perceived health and mental well‐being, respectively. Factor analysis and structural equation modelling on the Perceived Stress Scale replicated the reported two‐factor structure after excluding an insignificant item. Linear multiple regression analyses indicated that perceived stress was negatively associated with perceived health. Results showed that mental well‐being partially mediated the relationship between perceived stress and perceived health, although it is acknowledged that this association could be bidirectional. Findings from the present study suggest that future research could focus on reducing stress and improving mental well‐being to alleviate the effect of stress on health. Copyright © 2013 John Wiley & Sons, Ltd.     

Modified positioning of a smartphone based single-lead electrocardiogram device improves detection of atrial flutter

Introduction

The AliveCor Kardia Mobile (AKM) is a handheld, smartphone based cardiac rhythm monitor that records a lead-I electrocardiogram (ECG). Despite being efficacious for detection of atrial fibrillation (AF), it is unclear whether atrial flutter (AFL) may be misdiagnosed as sinus rhythm due to regular R-R intervals. We hypothesised that generating lead-II tracings through repositioning of the AKM may improve visualisation of flutter waves and clinician diagnosis of AFL compared to traditional lead-I tracings.

Can you rely on Treg cells on the rebound?

FoxP3⁺ regulatory T (Treg) cells comprise a highly dynamic population that restrains autoreactivity. Although complete or long‐term depletion of Foxp3⁺CD4⁺ Treg cells in adult mice has been shown to result in chronic inflammation and autoimmune disease, the impact of transient Treg‐cell depletion on self‐reactive responses is poorly defined. A new study published in this issue of the European Journal of Immunology [Eur. J. Immunol. 2014. 44: 3621–3631] shows that, although transient depletion of Treg cells in mice is swiftly followed by recovery of Treg‐cell numbers, the “rebounded” population fails to maintain tolerance, culminating in severe autoimmune gastritis. This commentary explores new questions about the quantitative and qualitative aspects of Treg‐cell function in immunological tolerance raised by this study and others.     

Specialized pro‐resolving lipid mediators in experimental periodontitis: A systematic review

Recently, several studies demonstrated the potential of using specialized pro‐resolving lipid mediators (SPMs), as a novel approach, in treating periodontitis in pre‐clinical models. This review aimed to systematically evaluate the biological actions of SPMs on periodontal tissues in animals with experimentally induced periodontitis. This systematic review was performed by following the Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Studies were searched in three databases. Meta‐analysis was not performed because of the data heterogeneity. Study quality was assessed using Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) Risk of Bias tool. Six studies using an experimental periodontitis model to test the efficacy of SPMs were selected. Resolvin E1 and lipoxins were topically applied to treat experimental periodontitis. Alveolar bone loss could be significantly prevented and regenerated by applying SPMs, when compared to the control group. The dosages of SPMs and the periods of disease induction varied based on the pre‐clinical model employed. Two studies further demonstrated the positive shift in microbial composition, in line with positive shift in inflammatory status, that are regulated by SPMs. Clinical studies are needed to optimize the application of SPMs in treating periodontal diseases in humans.     

Quantifying circulating hypoxia-induced RNA transcripts in maternal blood to determine in uterofetal hypoxic status

Background

Hypoxia in utero can lead to stillbirth and severe perinatal injury. While current prenatal tests can identify fetuses that are hypoxic, none can determine the severity of hypoxia/acidemia. We hypothesized a hypoxic/acidemic fetus would up-regulate and release hypoxia-induced mRNA from the fetoplacental unit into the maternal circulation, where they can be sampled and quantified. Furthermore, we hypothesized the abundance of hypoxia induced mRNA in the maternal circulation would correlate with severity of fetal hypoxia/acidemia in utero. We therefore examined whether abundance of hypoxia-induced mRNA in the maternal circulation correlates with the degree of fetal hypoxia in utero.

Methods

We performed a prospective study of two cohorts: 1) longitudinal study of pregnant women undergoing an induction of labor (labor induces acute fetal hypoxia) and 2) pregnancies complicated by severe preterm growth restriction (chronic fetal hypoxia). For each cohort, we correlated hypoxia induced mRNA in the maternal blood with degree of fetal hypoxia during its final moments in utero, evidenced by umbilical artery pH or lactate levels obtained at birth. Gestational tissues and maternal bloods were sampled and mRNAs quantified by microarray and RT-PCR.

Results

Hypoxia-induced mRNAs in maternal blood rose across labor, an event that induces acute fetal hypoxia. They exhibited a precipitous increase across the second stage of labor, a particularly hypoxic event. Importantly, a hypoxia gene score (sum of the relative expression of four hypoxia-induced genes) strongly correlated with fetal acidemia at birth. Hypoxia-induced mRNAs were also increased in the blood of women carrying severely growth restricted preterm fetuses, a condition of chronic fetal hypoxia. The hypoxia gene score correlated with the severity of ultrasound Doppler velocimetry abnormalities in fetal vessels. Importantly, the hypoxia gene score (derived from mRNA abundance in maternal blood) was significantly correlated with the degree of fetal acidemia at birth in this growth restriction cohort.

Conclusions

Abundance of mRNAs coding hypoxia-induced genes circulating in maternal blood strongly correlates with degree of fetal hypoxia/acidemia. Measuring hypoxia-induced mRNA in maternal blood may form the basis of a novel non-invasive test to clinically determine the degree of fetal hypoxia/acidemia while in utero.