Decreased VMAT2 in the pancreas of humans with type 2 diabetes mellitus measured in vivo by PET imaging

Aims/hypothesis

The progressive loss of beta cell function is part of the natural history of type 2 diabetes. Autopsy studies suggest that this is, in part, due to loss of beta cell mass (BCM), but this has not been confirmed in vivo. Non-invasive methods to quantify BCM may contribute to a better understanding of type 2 diabetes pathophysiology and the development of therapeutic strategies. In humans, the localisation of vesicular monoamine transporter type 2 (VMAT2) in beta cells and pancreatic polypeptide cells, with minimal expression in other exocrine or endocrine pancreatic cells, has led to its development as a measure of BCM. We used the VMAT2 tracer [¹⁸F]fluoropropyl-(+)-dihydrotetrabenazine to quantify BCM in humans with impaired glucose tolerance (prediabetes) or type 2 diabetes, and in healthy obese volunteers (HOV).

Methods

Dynamic positron emission tomography (PET) data were obtained for 4 h with metabolite-corrected arterial blood measurement in 16 HOV, five prediabetic and 17 type 2 diabetic participants. Eleven participants (six HOV and five with type 2 diabetes) underwent two abdominal PET/computed tomography (CT) scans for the assessment of test–retest variability. Standardised uptake value ratio (SUVR) was calculated in pancreatic subregions (head, body and tail), with the spleen as a reference region to determine non-specific tracer uptake at 3–4 h. The outcome measure SUVR minus 1 (SUVR-1) accounts for non-specific tracer uptake. Functional beta cell capacity was assessed by C-peptide release following standard (arginine stimulus test [AST]) and acute insulin response to the glucose-enhanced AST (AIRargMAX). Pearson correlation analysis was performed between the binding variables and the C-peptide AUC post-AST and post-AIRargMAX.

Results

Absolute test–retest variability (aTRV) was ≤15% for all regions. Variability and overlap of SUVR-1 was measured in all groups; HOV and participants with prediabetes and with type 2 diabetes. SUVR-1 showed significant positive correlations with AIRargMAX (all groups) in all pancreas subregions (whole pancreas p?=?0.009 and pancreas head p?=?0.009; body p?=?0.019 and tail p?=?0.023). SUVR-1 inversely correlated with HbA_1c (all groups) in the whole pancreas (p?=?0.033) and pancreas head (p?=?0.008). SUVR-1 also inversely correlated with years since diagnosis of type 2 diabetes in the pancreas head (p?=?0.049) and pancreas tail (p?=?0.035).

Conclusions/interpretation

The observed correlations of VMAT2 density in the pancreas and pancreas regions with years since diagnosis of type 2 diabetes, glycaemic control and beta cell function suggest that loss of BCM contributes to deficient insulin secretion in humans with type 2 diabetes.

     

Effects of intranasal oxytocin on pupil dilation indicate increased salience of socioaffective stimuli

To investigate the mechanisms by which oxytocin improves socioaffective processing, we measured behavioral and pupillometric data during a dynamic facial emotion recognition task. In a double‐blind between‐subjects design, 47 men received either 24 IU intranasal oxytocin (OXT) or a placebo (PLC). Participants in the OXT group recognized all facial expressions at lower intensity levels than did participants in the PLC group. Improved performance was accompanied by increased task‐related pupil dilation, indicating an increased recruitment of attentional resources. We also found increased pupil dilation during the processing of female compared with male faces. This gender‐specific stimulus effect diminished in the OXT group, in which pupil size specifically increased for male faces. Results suggest that improved emotion recognition after OXT treatment might be due to an intensified processing of stimuli that usually do not recruit much attention.     

The role of weight bias and role-modeling in medical students’ patient-centered communication with higher weight standardized patients

ObjectivePatients with obesity may experience less patient-centered care. We assessed whether medical students’ implicit/explicit weight-related attitudes and perceptions of normative attitudes are associated with patient-centered care for patients with obesity.MethodsThird and fourth year medical students (N = 111) at one medical school completed a survey and participated in a patient care scenario with a standardized patient with obesity. Encounters were coded for patient-centered behavior. Predictors of patient-centered behaviors were assessed.ResultsStudent perceptions that negative attitudes about patients with obesity are normative in medical school were significantly associated with poorer patient-centered behaviors, including lower attentiveness (b=?0.19, p = 0.01), friendliness (b=?0.28, p < 0.001), responsiveness (b=?0.21, p = 0.002), respectfulness (b=?0.17, p = 0.003), interactivity (b=?0.22, p = 0.003), likelihood of being recommended by observers (b=?0.34, p < 0.001), and patient-centeredness index scores (b=?0.16, p = 0.002). Student reported faculty role-modeling of discrimination against patients with obesity predicted lower friendliness (b=?0.16, p = 0.03), recommendation likelihood (b=?0.22, p = 0.04), and patient-centeredness index score (b=?0.12, p = 0.03).ConclusionsNegative normative attitudes and behaviors regarding obesity in the medical school environment may adversely influence the quality of patient-centered behaviors provided to patients with obesity.Practice implicationsEfforts to improve patient-centered communication quality among medical trainees may benefit from intervention to improve group normative attitudes about patients with obesity.     

Processes of knowing in the translation of a health communication intervention for dialysis patients awaiting kidney transplantation

ObjectiveTo strengthen patients’ health literacy and their role as active knowledge actors, we developed a health communication intervention including a film-viewing and counselling session for patients awaiting kidney transplantation. We aimed to explore processes of knowing in the translation of the intervention.MethodsWe applied an ethnographic research approach, observing nine intervention sessions with patients and dialysis nurses. Afterwards, the patients and the nurses were interviewed in-depth. Data were analysed using Engebretsen’s modified version of Lonergans’ four-step model of knowing.ResultsThe following knowing processes were identified: i) Knowing as meaning-making; ii) Knowing as acquiring confidence; and iii) Accessing professionals’ and peer experts’ knowledge. Divergent considerations were taken by the different knowledge actors, which had a direct influence on the knowing processes and knowledge translation.ConclusionsThe findings support active interactions between patients and healthcare providers in processes of knowing. These include self-conscious approaches and critical questioning in both parties.Practice implicationsFor transplant professionals, this study demonstrates knowing processes in a real-life context. It also spotlights professional skills and attitudes regarding the importance of self-conscious questioning and a critical interrogating position (for both patients and providers).     

Proton pump inhibitor use and risk for recurrent Clostridioides difficile infection: a systematic review and meta-analysis

ObjectivesProton pump inhibitor (PPI) therapy is a potentially modifiable risk factor for recurrent Clostridioides difficile infection (CDI). Citing an absence of clinical trials, many guidelines do not provide recommendations for addressing PPI management. Our aim was to perform an updated systematic review and meta-analysis evaluating the association between PPI use and recurrent CDI addressing prior methodological limitations.MethodsData sources were MEDLINE and EMBASE. Eligible studies were cohort and case–control studies; there were no restrictions on study setting or duration of follow-up. Participants were adults with prior CDI who did or did not receive PPI therapy and were assessed for recurrent CDI. Summary (unadjusted) odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random effects model. Prespecified subgroup analyses were performed to explore heterogeneity including study design, study quality, duration of follow-up, adjustment for confounders, and outcome definition.ResultsSixteen studies were included in the meta-analysis, comprising 57 477 patients with CDI, of whom 6870 (12%) received PPIs. The rate of recurrent CDI was 24% in patients treated with PPIs versus 18% in those who were not. A meta-analysis that pooled unadjusted odds ratios demonstrated higher odds of recurrent CDI in patients who received PPIs (OR 1.69, 95%CI 1.46–1.96) versus those who did not. There was moderate heterogeneity between studies (I² 56%); however, a sensitivity analysis restricted to studies with 56 days of follow-up substantially reduced the heterogeneity (OR 1.59, 95%CI 1.36–1.85; I² 12%). An analysis restricted to multivariate studies that combined adjusted ORs also demonstrated higher odds of recurrent CDI in patients who received PPIs (OR 1.49, 95%CI 1.12–2.00). No publication bias was identified.ConclusionsWe found significantly higher odds of recurrent CDI among users of PPIs that persisted across multiple sensitivity analyses. These results support stronger recommendations for PPI stewardship at CDI diagnosis.