Use of Diabetes Technologies and Retinopathy in Adults With Type 1 Diabetes.

Importance: Diabetic retinopathy (DR) is a complication of diabetes that can lead to vision loss. Outcomes of continuous glucose monitoring (CGM) and insulin pump use in DR are not well understood. Objective: To assess the use of CGM, insulin pump, or both, and DR and proliferative diabetic retinopathy (PDR) in adults with type 1 diabetes (T1D). Design, Setting, and Participants: A retrospective cohort study of adults with T1D in a tertiary diabetes center and ophthalmology center was conducted from 2013 to 2021, with data analysis performed from June 2022 to April 2023. Exposure: Use of diabetes technologies, including insulin pump, CGM, and both CGM and insulin pump. Main Outcomes and Measures: The primary outcome was development of DR or PDR. A secondary outcome was the progression of DR for patients in the longitudinal cohort. Multivariable logistic regression models assessed for development of DR and PDR and association with CGM and insulin pump use. Results: A total of 550 adults with T1D were included (median age, 40 [IQR, 28-54] years; 54.4% female; 24.5% Black or African American; and 68.4% White), with a median duration of diabetes of 20 (IQR, 10-30) years, and median hemoglobin A1c (HbA1c) of 7.8% (IQR, 7.0%-8.9%). Overall, 62.7% patients used CGM, 58.2% used an insulin pump, and 47.5% used both; 44% (244 of 550) of the participants had DR at any point during the study. On univariate analysis, CGM use was associated with lower odds of DR and PDR, and CGM with pump was associated with lower odds of PDR (all P < .05), compared with no CGM use. Multivariable logistic regression adjusting for age, sex, race and ethnicity, diabetes duration, microvascular and macrovascular complications, insurance type, and mean HbA1c, showed that CGM was associated with lower odds of DR (odds ratio [OR], 0.52; 95% CI, 0.32-0.84; P = .008) and PDR (OR, 0.42; 95% CI, 0.23-0.75; P = .004), compared with no CGM use. In the longitudinal analysis of participants without baseline PDR, 79 of 363 patients (21.8%) had progression of DR during the study. Conclusions and Relevance: In this cohort study of adults with T1D, CGM use was associated with lower odds of developing DR and PDR, even after adjusting for HbA1c. These findings suggest that CGM may be useful for diabetes management to mitigate risk for DR and PDR.

Racial Disparities in Access and Use of Diabetes Technology Among Adult Patients With Type 1 Diabetes in a U.S. Academic Medical Center.

OBJECTIVE: Recent studies highlight racial disparities in insulin pump (PUMP) and continuous glucose monitor (CGM) use in children and adolescents with type 1 diabetes (T1D). This study explored racial disparities in diabetes technology among adult patients with T1D. RESEARCH DESIGN AND METHODS: This was a retrospective clinic-based cohort study of adult patients with T1D seen consecutively from April 2013 to January 2020. Race was categorized into non-Black (reference group) and Black. The primary outcomes were baseline and prevalent technology use, rates of diabetes technology discussions (CGMdiscn, PUMPdiscn), and prescribing (CGMrx, PUMPrx). Multivariable logistic regression analysis evaluated the association of technology discussions and prescribing with race, adjusting for social determinants of health and diabetes outcomes. RESULTS: Among 1,258 adults with T1D, baseline technology use was significantly lower for Black compared with non-Black patients (7.9% vs. 30.3% for CGM; 18.7% vs. 49.6% for PUMP), as was prevalent use (43.6% vs. 72.1% for CGM; 30.7% vs. 64.2% for PUMP). Black patients had adjusted odds ratios (aORs) of 0.51 (95% CI 0.29, 0.90) for CGMdiscn and 0.61 (95% CI 0.41, 0.93) for CGMrx. Black patients had aORs of 0.74 (95% CI 0.44, 1.25) for PUMPdiscn and 0.40 (95% CI, 0.22, 0.70) for PUMPrx. Neighborhood context, insurance, marital and employment status, and number of clinic visits were also associated with the outcomes. CONCLUSIONS: Significant racial disparities were observed in discussions, prescribing, and use of diabetes technology. Further research is needed to identify the causes behind these disparities and develop and evaluate strategies to reduce them.

Effects of Alcohol Withdrawal on Sleep Macroarchitecture and Microarchitecture in Female and Male Rats.

The prevalence of sleep disruptions is higher among people with alcohol use disorder (AUD), particularly during alcohol withdrawal, compared to non-AUD individuals. Although women generally have a higher risk of developing sleep disorders, few studies have investigated sex differences in sleep disruptions following chronic alcohol exposure. The present study examined sleep macroarchitecture (time spent asleep or awake and sleep onset latency) and microarchitecture (bout rate and duration and sleep spindle characterization) prior to alcohol vapor exposure (baseline), during acute withdrawal, and through protracted abstinence in female and male rats. Females and males showed reduced time in rapid eye movement (REM) sleep during acute withdrawal, which returned to baseline levels during protracted abstinence. REM sleep onset latency was decreased during protracted abstinence in females only. Furthermore, there was a sex difference observed in overall REM sleep bout rate. Although there were no changes in non-REM sleep time, or to non-REM sleep bout rate or duration, there was an increase in non-REM sleep intra-spindle frequency during acute withdrawal in both females and males. Finally, there was increased wakefulness time and bout duration during acute withdrawal in both females and males. The results demonstrate both macroarchitectural and microarchitectural changes in sleep following chronic alcohol exposure, particularly during acute withdrawal, suggesting the need for therapeutic interventions for sleep disturbances during withdrawal in individuals with AUD. Furthermore, sex differences were observed in REM sleep, highlighting the importance of including both sexes in future alcohol-related sleep studies.

Impact of Effortful Word Recognition on Supportive Neural Systems Measured by Alpha and Theta Power.

OBJECTIVES: The goal of this study was to use theta and alpha electroencephalography (EEG) frequency power and self-report measures to examine performance monitoring, cognitive inhibition, and perceived effort required for speech understanding in noise. It was hypothesized that with a linear increase in word recognition task difficulty, there would be a linear increase in listening effort and word recognition performance would decrease in the challenging conditions. In addition, theta and alpha power would have an inverted U-shape across easy to challenging listening conditions. The inverted U-shape would reflect the neural underpinnings of listening effort that cannot be measured by task performance alone. DESIGN: EEG data were collected in 34 normal-hearing adults (18 to 33 years old) during the Words-In-Noise (WIN) test, which was presented in sound field. EEG frequency data were averaged and analyzed at three frontal channels for theta power (4 to 8 Hz), which is thought to reflect performance monitoring, and three parietal channels for alpha power (8 to 12 Hz), which is thought to reflect cognitive inhibition. A ten-point visual analog scale was administered after each WIN signal-to-noise ratio (SNR) condition to capture self-reported required and invested listening effort (RLE and ILE, respectively). The WIN SNR conditions were presented in descending and random order. RESULTS: The SNR presentation (descending or random SNR) had a null effect on word recognition performance; however, presentation did have an effect on theta power, alpha power, and ILE. When controlling for presentation, there were significant effects of SNR and presentation on both theta and alpha frequency power. Theta and alpha power had an inverted U-shape as a function of SNR from easy to challenging, with peak power in the moderate SNR conditions. RLE and ILE both significantly increased as task difficulty increased as expected; however, RLE showed a stronger relation to task performance than ILE. Alpha power was a significant predictor of RLE, ILE, and WIN performance when controlling for SNR. CONCLUSIONS: The elevated theta and alpha power in the easy to moderate SNRs and alpha power predicting self-reported listening effort suggest the activation of supportive neural systems during word recognition that could be considered a marker of listening effort. Moreover, the measures of neural support systems and listening effort were independent from task performance, which is a key element to further understanding the neural bases for listening effort. In the context of the broader literature, these results are consistent with (1) a parietal alpha role in supporting inhibitory control to suppress irrelevant information and (2) a frontal theta role in supporting performance monitoring in difficult listening conditions where speech recognition is feasible.

Accumulation of long-chain fatty acids in the tumor microenvironment drives dysfunction in intrapancreatic CD8+ T cells.

CD8+ T cells are master effectors of antitumor immunity, and their presence at tumor sites correlates with favorable outcomes. However, metabolic constraints imposed by the tumor microenvironment (TME) can dampen their ability to control tumor progression. We describe lipid accumulation in the TME areas of pancreatic ductal adenocarcinoma (PDA) populated by CD8+ T cells infiltrating both murine and human tumors. In this lipid-rich but otherwise nutrient-poor TME, access to using lipid metabolism becomes particularly valuable for sustaining cell functions. Here, we found that intrapancreatic CD8+ T cells progressively accumulate specific long-chain fatty acids (LCFAs), which, rather than provide a fuel source, impair their mitochondrial function and trigger major transcriptional reprogramming of pathways involved in lipid metabolism, with the subsequent reduction of fatty acid catabolism. In particular, intrapancreatic CD8+ T cells specifically exhibit down-regulation of the very-long-chain acyl-CoA dehydrogenase (VLCAD) enzyme, which exacerbates accumulation of LCFAs and very-long-chain fatty acids (VLCFAs) that mediate lipotoxicity. Metabolic reprogramming of tumor-specific T cells through enforced expression of ACADVL enabled enhanced intratumoral T cell survival and persistence in an engineered mouse model of PDA, overcoming one of the major hurdles to immunotherapy for PDA.

Discovering New Lipidomic Features Using Cell Type Specific Fluorophore Expression to Provide Spatial and Biological Specificity in a Multimodal Workflow with MALDI Imaging Mass Spectrometry.

Identifying the spatial distributions of biomolecules in tissue is crucial for understanding integrated function. Imaging mass spectrometry (IMS) allows simultaneous mapping of thousands of biosynthetic products such as lipids but has needed a means of identifying specific cell-types or functional states to correlate with molecular localization. We report, here, advances starting from identity marking with a genetically encoded fluorophore. The fluorescence emission data were integrated with IMS data through multimodal image processing with advanced registration techniques and data-driven image fusion. In an unbiased analysis of spleens, this integrated technology enabled identification of ether lipid species preferentially enriched in germinal centers. We propose that this use of genetic marking for microanatomical regions of interest can be paired with molecular information from IMS for any tissue, cell-type, or activity state for which fluorescence is driven by a gene-tracking allele and ultimately with outputs of other means of spatial mapping.

A Path From Childhood Sensory Processing Disorder to Anxiety Disorders: The Mediating Role of Emotion Dysregulation and Adult Sensory Processing Disorder Symptoms.

Although maladaptive sensory processing has been observed among individuals with persistent heightened anxiety, it is unclear if difficulties processing sensory input early in life lead to anxiety disorders in adulthood and what mechanisms would drive this progression. In a transdiagnostic clinical sample of 231 adults characterized by heightened difficulties with emotion regulation, the present study sought to examine whether: (a) childhood sensory processing disorder (SPD) symptoms predict an increased probability of an anxiety disorder diagnosis in adulthood; and (b) difficulties with emotion regulation and adult SPD symptoms mediate this relationship. Participants were administered the Structured Clinical Interview for Axis-I disorders and self-reported symptoms of SPD experienced in childhood and adulthood. Results suggested that childhood SPD symptoms were significantly associated with a higher likelihood of a lifetime anxiety disorder diagnosis. Difficulties with emotion regulation fully mediated the relationship between childhood SPD and (a) any anxiety disorder in adulthood and, specifically (b) current generalized anxiety disorder (GAD). Further, we found evidence for a candidate model accounting for the relationship among childhood SPD, adulthood SPD, difficulties with emotion regulation, and anxiety disorders in adulthood. Specifically, our data indicated that high symptoms of SPD in childhood may lead to high SPD symptoms in adulthood, which then lead to high emotion dysregulation, ultimately conferring vulnerability for an anxiety disorder diagnosis. Taken together, these findings provide preliminary evidence for how sensory processing impairments in childhood may relate to anxiety through difficulties regulating emotion regulation.

Community member and faith leader perspectives on the process of building trusting relationships between communities and researchers.

In the first phase of this research, we conducted, audio-recorded, and transcribed seven focus groups with more than 50 English- or Spanish-speaking women of childbearing age. Qualitative analysis revealed the following themes: (1) expectation that participation would involve relationships based on trust that is built over time and impacted by cultural factors; (2) perceived characteristics of research staff that would help facilitate the development of trusting relationships; (3) perceptions about the location of the visits that may affect trust; (4) perceptions of a research study and trust for the institution conducting the study may affect trust; (5) connecting the study to larger communities, including faith communities, could affect trust and willingness to participate. In the second phase of this research, we conducted, recorded, transcribed, and analyzed interviews with leaders from diverse faith communities to explore the potential for research partnerships between researchers and faith communities. In addition to confirming themes identified in focus groups, faith leaders described an openness to research partnerships between the university and faith communities and considerations for the formation of these partnerships. Faith leaders noted the importance of finding common ground with researchers, establishing and maintaining trusting relationships, and committing to open, bidirectional communication.

Maternal perspectives on the return of genetic results: context matters.

The objectives of this study were to study maternal preferences for the return of their child's genetic results and to describe the experiences, perceptions, attitudes, and values that are brought to bear when individuals from different racial and cultural backgrounds consider participating in genetic research. We recruited women with diverse sociodemographic profiles to participate in seven focus groups. Twenty-eight percent of participants self-identified as Hispanic; 49% as White, non-Hispanic; and 21% as Asian or Asian American. Focus groups were conducted in English or Spanish and were audio-recorded and transcribed verbatim. Transcripts were analyzed using qualitative thematic methods. Results indicated that preferences and decisions regarding the return of results may depend on both research and individual contextual factors. Participants understood the return of results as a complex issue, where individual and cultural differences in preferences are certain to arise. Another key finding was that participants desired an interpersonal, dynamic, flexible process that accommodated individual preferences and contextual differences for returning results. Our findings indicate a need to have well-developed systems for allowing participants to make and change over time their choices regarding the return of their child's genetic results.

Diverse perceptions of the informed consent process: implications for the recruitment and participation of diverse communities in the National Children's Study.

We examined the experiences, perceptions, and values that are brought to bear when individuals from different ethnic and cultural backgrounds consider participating in health research. Fifty-three women from Latino, Asian American, Middle Eastern, or Non-Latino, White backgrounds participated in seven English or Spanish focus groups facilitated by trained investigators using a standard protocol. Investigators described the National Children's Study (NCS) and then asked questions to elicit potential concerns, expectations, and informational needs. Group sessions were audio-recorded, transcribed verbatim, and analyzed using qualitative thematic methods. A major theme that emerged during focus groups was participant self-identification as a member of a cultural group or community when raising issues that would influence their decision to participate in research. A related theme was the belief by some that communities may differ in the ease of participation in the NCS. Identified themes related to the informed consent process included perceived risks, anticipated burden, perceived benefits, informational needs, and decision-making strategies. Although themes were shared across groups, there were cultural differences within themes. Findings indicated that individuals from diverse backgrounds may have different perspectives on and expectations for the research process. To effectively recruit representative samples, it will be important to address a range of issues relevant for informed consent and to consider the impact of participation on both individuals and communities.