Relationship of muscle sympathetic nerve activity to insulin sensitivity

Purpose

An association between insulin resistance and activation of the sympathetic nervous system has been reported in previous studies. However, potential interactions between insulin sensitivity and sympathetic neural mechanisms in healthy people remain poorly understood. We conducted a study to determine the relationship between sympathetic activity and insulin resistance in young, healthy humans.

Methods

Thirty-seven healthy adults (18–35 years, BMI <28 kg m^?2) were studied. Resting muscle sympathetic nerve activity (MSNA) was measured with microneurography and insulin sensitivity of glucose and free fatty acid metabolism was measured during a hyperinsulinemic-euglycemic clamp with two levels of insulin.

Results

During lower doses of insulin, we found a small association between lower insulin sensitivity and higher MSNA (P < 0.05) but age was a cofactor in this relationship. Overall, we found no difference in insulin sensitivity between groups of low and high MSNA, but when women were analyzed separately, insulin sensitivity was lower in the high MSNA group compared with the low MSNA group of women.

Conclusions

These data suggest that MSNA and insulin sensitivity are only weakly associated with young healthy individuals and that age and sex may be important modifiers of this relationship.     

Do current therapeutic anti-Aβ antibodies for Alzheimer’s disease engage the target?

Reducing amyloid-β peptide (Aβ) burden at the pre-symptomatic stages of Alzheimer’s disease (AD) is currently the advocated clinical strategy for treating this disease. The most developed method for targeting Aβ is the use of monoclonal antibodies including bapineuzumab, solanezumab and crenezumab. We have synthesized these antibodies and used surface plasmon resonance (SPR) and mass spectrometry to characterize and compare the ability of these antibodies to target Aβ in transgenic mouse tissue as well as human AD tissue. SPR analysis showed that the antibodies were able to bind Aβ with high affinity. All of the antibodies were able to bind Aβ in mouse tissue. However, significant differences were observed in human brain tissue. While bapineuzumab was able to capture a variety of N-terminally truncated Aβ species, the Aβ detected using solanezumab was barely above detection limits while crenezumab did not detect any Aβ. None of the antibodies were able to detect any Aβ species in human blood. Immunoprecipitation experiments using plasma from AD subjects showed that both solanezumab and crenezumab have extensive cross-reactivity with non-Aβ related proteins. Bapineuzumab demonstrated target engagement with brain Aβ, consistent with published clinical data. Solanezumab and crenezumab did not, most likely as a result of a lack of specificity due to cross-reactivity with other proteins containing epitope overlap. This lack of target engagement raises questions as to whether solanezumab and crenezumab are suitable drug candidates for the preventative clinical trials for AD.     

Screening for Depression and High Utilization of Health Care Resources Among Patients in Primary Care

The study aims to evaluate the prevalence of depression and the severity of depressive symptoms among primary care patients, who are high utilizers (HU) of health care resources. A cross-sectional, two-stage design was applied to screen for depression using the Brief Psychiatric Health Questionnaire and the Diagnostic Expert System for Psychiatric Disorders. A total of 38 primary care physicians accredited to practice in Berlin and Potsdam in Germany participated in the study. A total of 1,775 patients participated, 507 were identified as HU, 182 (36 %) of these were depressed compared to 81 (11 %) of the typical utilizers (p < 0.001). The depression score was higher and acute suicidality was more prevalent in HU than in typical utilizers (p < 0.001). Our results suggest that HU represent a population with a high prevalence of depression in primary care and should be considered for routine depression screening.     

Emotion dysregulation as a maintenance factor of borderline personality disorder features

We examined within-individual changes in emotion dysregulation over the course of one year as a maintenance factor of borderline personality disorder (BPD) features. We evaluated the extent to which (1) BPD symptom severity at baseline predicted within-individual changes in emotion dysregulation and (2) within-individual changes in emotion dysregulation predicted four BPD features at 12-month follow-up: affective instability, identity disturbances, negative relationships, and impulsivity. The specificity of emotion dysregulation as a maintaining mechanism of BPD features was examined by controlling for a competing intervening variable, interpersonal conflict. BPD symptoms at baseline predicted overall level and increasing emotion dysregulation. Additionally, increasing emotion dysregulation predicted all four BPD features at 12-month follow-up after controlling for BPD symptoms at baseline. Further, overall level of emotion dysregulation mediated the association between BPD symptom severity at baseline and both affective instability and identity disturbance at 12-month follow-up, consistent with the notion of emotion dysregulation as a maintenance factor. Future research on the malleability of emotion dysregulation in laboratory paradigms and its effects on short-term changes in BPD features is needed to inform interventions.