Three linked variants have opposing regulatory effects on isovaleryl-CoA dehydrogenase gene expression.

While genome-wide association studies (GWAS) and positive selection scans identify genomic loci driving human phenotypic diversity, functional validation is required to discover the variant(s) responsible. We dissected the IVD gene locus-which encodes the isovaleryl-CoA dehydrogenase enzyme-implicated by selection statistics, multiple GWAS, and clinical genetics as important to function and fitness. We combined luciferase assays, CRISPR/Cas9 genome-editing, massively parallel reporter assays (MPRA), and a deletion tiling MPRA strategy across regulatory loci. We identified three regulatory variants, including an indel, that may underpin GWAS signals for pulmonary fibrosis and testosterone, and that are linked on a positively selected haplotype in the Japanese population. These regulatory variants exhibit synergistic and opposing effects on IVD expression experimentally. Alleles at these variants lie on a haplotype tagged by the variant most strongly associated with IVD expression and metabolites, but with no functional evidence itself. This work demonstrates how comprehensive functional investigation and multiple technologies are needed to discover the true genetic drivers of phenotypic diversity.

Real-world use of glucagon-like peptide-1 receptor agonists in youth with type 2 diabetes is associated with short-term improvements in HbA1c.

AIM: To assess the short-term, real-world use and effectiveness of glucagon-like peptide-1 receptor agonist (GLP-1RA) medications in the management of type 2 diabetes (T2D) in a diverse cohort of youth. METHODS: This multicentre retrospective study analysed youth prescribed a GLP-1RA for the management of T2D at two academic paediatric diabetes centres prior to June 2022. Change in HbA1c and insulin use from baseline to first (median 91 days) and second (median 190 days) follow-up were evaluated for those taking a GLP-1RA. Multivariable linear mixed effects models adjusting for baseline sex, age, race/ethnicity, insurance, insulin regimen, metformin regimen, GLP-1RA dosing frequency and the body mass index Z-score (BMI-Z) examined the change in HbA1c for participants for up to 6 months after baseline. RESULTS: A total of 136 patients with T2D (median age 16.1 [interquartile range 13.9-18.0] years, 54% female, 56% non-Hispanic Black, 24% Hispanic, 77% with public insurance) were prescribed GLP-1RAs and taking them at first or second follow-up. Median HbA1c decreased from 7.9% to 7.6% (P < .001) at a median follow-up of 91 days (n = 109) and, among those with HbA1c available at baseline and second follow-up (n = 83), from 8.4% to 7.4%. The proportion of patients prescribed insulin decreased from baseline to the first follow-up visit (basal 69% to 60% [P = .008], prandial 46% to 38% [P = .03]). In multivariable analysis, there was a mean decrease in HbA1c by 0.09 percentage points per month (P = .005, 95% confidence interval -0.15, -0.03). CONCLUSIONS: Real-world use of GLP-1RAs in youth with T2D is associated with decreased HbA1c levels, despite challenges with access and adherence. GLP-1RA treatment may reduce insulin doses for youth with T2D.

Discussing systemic racism and racial privilege at a large, academic health center using a modified privilege walk.

BACKGROUND: There is a motivation for organizations to understand race and racism from the perspective of minoritized individuals. Academic health centers (AHC) are ideal organizations to have these conversations as they educate healthcare providers, support research in health disparities, and care for diverse patients. METHODS: We piloted and evaluated a virtual Modified Privilege Walk (MPW) with faculty, staff, and students at an AHC in July 2020 to promote difficult conversations about race/racism, social class, and privilege. Each MPW session was voluntary, held virtually over Zoom, and lasted one hour and thirty minutes. Before attending, participants answered questions based on their race/ethnicity and social class to calculate a "privilege score." After each session, attendees were asked to complete an evaluation survey. RESULTS: There were five virtual MPWs with 132 attendees, and 74 participants completed an evaluation survey (56% response rate). Many respondents were students (n = 29, 39.2%). Most respondents either agreed (n = 36, 48.6%) or strongly agreed (n = 32, 43.2%) that the virtual MPW positively impacted how they will interact with those of a different race/ethnicity. Attendees requested having more virtual MPWs with leadership, incorporating virtual MPWs in various program curricula, and requiring new employees to participate. CONCLUSIONS: American organizations, particularly AHCs, should provide safe spaces and support these discussions surrounding race and racism as many were founded, built, or operated during a time of free labor and segregation that exerted power and control over minoritized individuals. Authors provide recommendations to dismantle organizational racism and support minoritized employees, patients, and students.

Brief Pictorial Quizzes to Assess Carbohydrate Counting and Nutrition Knowledge in Youth With Type 1 Diabetes.

Available assessments of patient nutrition knowledge and carbohydrate counting ability are lengthy. This article reports on a study to implement and validate a series of brief nutrition quizzes of varying difficulty for use in pediatric type 1 diabetes. Among 129 youth with type 1 diabetes, participants completed an average of 2.4 ± 1 of the six quizzes, with a median score of 4.7 of 5. Higher quiz scores were associated with lower A1C (P <0.001), higher parental education (P = 0.02), and higher income (P = 0.01). Such quizzes can help to identify knowledge gaps and provide opportunities for education, which may improve glycemic outcomes in youth with type 1 diabetes.

African-Lineage Zika Virus Replication Dynamics and Maternal-Fetal Interface Infection in Pregnant Rhesus Macaques.

Following the Zika virus (ZIKV) outbreak in the Americas, ZIKV was causally associated with microcephaly and a range of neurological and developmental symptoms, termed congenital Zika syndrome (CZS). The viruses responsible for this outbreak belonged to the Asian lineage of ZIKV. However, in vitro and in vivo studies assessing the pathogenesis of African-lineage ZIKV demonstrated that African-lineage isolates often replicated to high titers and caused more-severe pathology than Asian-lineage isolates. To date, the pathogenesis of African-lineage ZIKV in a translational model, particularly during pregnancy, has not been rigorously characterized. Here, we infected four pregnant rhesus macaques with a low-passage-number strain of African-lineage ZIKV and compared its pathogenesis to those for a cohort of four pregnant rhesus macaques infected with an Asian-lineage isolate and a cohort of mock-inoculated controls. The viral replication kinetics for the two experimental groups were not significantly different, and both groups developed robust neutralizing antibody titers above levels considered to be protective. There was no evidence of significant fetal head growth restriction or gross fetal harm at delivery (1 to 1.5 weeks prior to full term) in either group. However, a significantly higher burden of ZIKV viral RNA (vRNA) was found in the maternal-fetal interface tissues of the macaques exposed to an African-lineage isolate. Our findings suggest that ZIKV of any genetic lineage poses a threat to pregnant individuals and their infants. IMPORTANCE ZIKV was first identified in 1947 in Africa, but most of our knowledge of ZIKV is based on studies of the distinct Asian genetic lineage, which caused the outbreak in the Americas in 2015 to 2016. In its most recent update, the WHO stated that improved understanding of African-lineage ZIKV pathogenesis during pregnancy must be a priority. The recent detection of African-lineage isolates in Brazil underscores the need to understand the impact of these viruses. Here, we provide the first comprehensive assessment of African-lineage ZIKV infection during pregnancy in a translational nonhuman primate model. We show that African-lineage isolates replicate with kinetics similar to those of Asian-lineage isolates and can infect the placenta. However, there was no evidence of more-severe outcomes with African-lineage isolates. Our results highlight both the threat that African-lineage ZIKV poses to pregnant individuals and their infants and the need for epidemiological and translational in vivo studies with African-lineage ZIKV.

The Coronavirus Disease 2019 Pandemic is Associated with a Substantial Rise in Frequency and Severity of Presentation of Youth-Onset Type 2 Diabetes.

OBJECTIVES: To evaluate the frequency and severity of new cases of youth-onset type 2 diabetes in the US during the first year of the pandemic compared with the mean of the previous 2 years. STUDY DESIGN: Multicenter (n = 24 centers), hospital-based, retrospective chart review. Youth aged ≤21 years with newly diagnosed type 2 diabetes between March 2018 and February 2021, body mass index ≥85th percentile, and negative pancreatic autoantibodies were included. Demographic and clinical data, including case numbers and frequency of metabolic decompensation, were compared between groups. RESULTS: A total of 3113 youth (mean [SD] 14.4 [2.4] years, 50.5% female, 40.4% Hispanic, 32.7% Black, 14.5% non-Hispanic White) were assessed. New cases of type 2 diabetes increased by 77.2% in the year during the pandemic (n = 1463) compared with the mean of the previous 2 years, 2019 (n = 886) and 2018 (n = 765). The likelihood of presenting with metabolic decompensation and severe diabetic ketoacidosis also increased significantly during the pandemic. CONCLUSIONS: The burden of newly diagnosed youth-onset type 2 diabetes increased significantly during the coronavirus disease 2019 pandemic, resulting in enormous strain on pediatric diabetes health care providers, patients, and families. Whether the increase was caused by coronavirus disease 2019 infection, or just associated with environmental changes and stressors during the pandemic is unclear. Further studies are needed to determine whether this rise is limited to the US and whether it will persist over time.

Measuring the impact of the Affordable Care Act Medicaid expansion on access to primary care using an interrupted time series approach.

BACKGROUND: The Patient Protection and Affordable Care Act of 2010, commonly referred to as the Affordable Care Act (ACA), was created to increase access to primary care, improve quality of care, and decrease healthcare costs. A key provision in the law that mandated expansion of state Medicaid programme changed when states were given the option to voluntarily expand Medicaid. Our study sought to measure the impact of ACA Medicaid expansion on preventable hospitalization (PH) rates, a measure of access to primary care. METHODS: We performed an interrupted time series analysis of quarterly hospitalization rates across eight states from 2012 to 2015. Segmented regression analysis was utilized to determine the impact of policy reform on PH rates. RESULTS: The Affordable Care Act's Medicaid expansion led to decreased rates of PH (improved access to care); however, the finding was not significant (coefficient estimate: -0.0059, CI -0.0225, 0.0107, p = 0.4856). Healthcare system characteristics, such as Medicaid spending per enrollee and Medicaid income eligibility, were associated with a significant decrease in rates of PH (improved access to care). However, the Medicaid-to-Medicare fee index (physician reimbursement) and states with a Democratic state legislature had a significant increase in rates of PH (poor access to care). CONCLUSION: Health policy reform and healthcare delivery characteristics impact access to care. Researchers should continue evaluating such policy changes across more states over longer periods of time. Researchers should translate these findings into cost analysis for state policy-makers to make better-informed decisions for their constituents. CONTRIBUTION TO KNOWLEDGE: Ambulatory care-sensitive conditions are a feasible method for evaluating policy and measuring access to primary care. Policy alone cannot improve access to care. Other factors (trust, communication, policy-makers' motivations and objectives, etc.) must be addressed to improve access.

Many ways to die, one way to arrive: how selection acts through pregnancy.

When considering selective forces shaping human evolution, the importance of pregnancy to fitness should not be underestimated. Although specific mortality factors may only impact upon a fraction of the population, birth is a funnel through which all individuals must pass. Human pregnancy places exceptional energetic, physical, and immunological demands on the mother to accommodate the needs of the fetus, making the woman more vulnerable during this time-period. Here, we examine how metabolic imbalances, infectious diseases, oxygen deficiency, and nutrient levels in pregnancy can exert selective pressures on women and their unborn offspring. Numerous candidate genes under selection are being revealed by next-generation sequencing, providing the opportunity to study further the relationship between selection and pregnancy. This relationship is important to consider to gain insight into recent human adaptations to unique diets and environments worldwide.

The Fitbit Fault Line: Two Proposals to Protect Health and Fitness Data at Work.

Employers are collecting and using their employees' health data, mined from wearable fitness devices and health apps, in new, profitable, and barely regulated ways. The importance of protecting employee health and fitness data will grow exponentially in the future. This is the moment for a robust discussion of how law can better protect employees from the potential misuse of their health data. While scholars have just begun to examine the problem of health data privacy, this Article contributes to the academic literature in three important ways. First, it analyzes the convergence of three trends resulting in an unprecedented growth of health-related data: the Internet of Things, the Quantified Self movement, and the Rise of Health Platforms. Second, it describes the insufficiencies of specific data privacy laws and federal agency actions in the context of protecting employee health data from employer misuse. Finally, it provides two detailed and workable solutions for remedying the current lack of protection of employee health data that will realign employer use with reasonable expectations of health and fitness privacy. The Article proceeds in four Parts. Part I describes the growth of self-monitoring apps, devices, and other sensor-enabled technology that can monitor a wide range of data related to an employee's health and fitness and the relationship of this growth to both the Quantified Self movement and the Internet of Things. Part II explains the increasing use of employee monitoring through a wide range of sensors, including wearable devices, and the potential uses of that health and fitness data. Part III explores the various regulations and agency actions that might protect employees from the potential misuse of their health and fitness data and the shortcomings of each. Part IV proposes two specific measures that would help ameliorate the ineffective legal protections that currently exist in this context. In order to improve employee notice of and control over the disclosure of their health data, I recommend the adoption of a mandatory privacy labeling law for health-related devices and apps to be enacted and enforced by the Federal Trade Commission (FTC). As a complementary measure, I also recommend that be amended so that its protections extend to the health-related data that employers may acquire about their employees. The Article concludes with suggestions for additional scholarly discussion.

The effects of supplemental dietary chitosan on broiler performance and myopathic features of white striping.

White striping (WS) is a common myopathy seen in fast-growing broilers. Studies have demonstrated that chitosan is effective as an antioxidant and has antiobesity and fat-absorption reduction properties. We hypothesized that the dietary supplementation of chitosan would have similar effects when fed to fast-growing broilers and would thus lower WS incidence and improve meat quality. One hundred twenty-six broilers were fed corn-soy diets. The grower and finisher diets contained either 0, 0.2, or 0.4% chitosan. After a 6 wk growth period, birds were euthanized, and then WS and gross pathology scores were assessed. Pectoralis major tissues were collected to evaluate cook loss, drip loss, histopathology scores, and the gene expression of CCR7, LECT2, CD36, PPARG, and PTGS2. There were no significant differences between the broiler weights, thus chitosan did not appear to compromise the overall growth of the broilers. Female broilers fed 0.4% chitosan had the lowest WS incidence, while male broiler fed 0.4% chitosan had the least cook loss. However, gene expression analyses did not offer insight into any grossly or histologically visualized differences in the muscles. Thus, while we can postulate that chitosan could have some positive effect in reducing WS incidence and improving meat quality, further studies are required to better scrutinize the mechanisms by which chitosan affects WS and other such myopathies in fast-growing broilers.

Patient Perceptions of Audio-Only Versus Video Telehealth Visits: A Qualitative Study Among Patients in an Academic Medical Center Setting.

Introduction: Telehealth utilization surged during the COVID-19 pandemic, offering expanded health care access. Audio-only visits emerged as a crucial tool for patients facing technology or connectivity barriers to still use telehealth. This qualitative study aims to better understand patient perceptions of audio-only versus video telehealth visits during the COVID-19 pandemic, and how patients perceive the role of each in their overall health care. Methods: Semi-structured interviews were conducted with 14 adult patients seeking care at an academic medical center located in the Southeast region of the United States. Patients had experienced both an audio-only and video telehealth visit within the past 6 months. Topics covered in the interview included comfort, preference, quality, and communication during each type of visit. Interviews were transcribed verbatim, coded, and analyzed using a general inductive approach. Results: Participants valued having both modalities available largely due to convenience and saw these visits as supplemental or supporting their in-person care. Preferences for visit types were varied among participants and were context-specific, influenced by visit purpose and provider rapport. Patients viewed audio-only visits favorably for informational follow-ups and highlighted their convenience, particularly for multitasking and caregiving duties. In contrast, video visits were seen as more effective for communication due to visual cues and better suited for demonstrating health conditions. Audio-only visits were also seen as less technology-dependent and served as a vital back-up to failed video encounters. Discussion: Despite varied preferences, patients perceived both modalities as complementary to in-person care. Concerns around the quality of care were mitigated by patients' and providers' judicious use of visit types based on clinical appropriateness and existing rapport. The results emphasize the necessity and flexibility of audio-only visits in ensuring equitable access to telehealth, especially for those with technology limitations or demanding responsibilities. To maintain the access and convenience afforded by telehealth and ensure these benefits are offered equitably, policy makers and health care organizations must continue to provide flexible telehealth options, including audio-only visits.

Dermal injury drives a skin to gut axis that disrupts the intestinal microbiome and intestinal immune homeostasis in mice.

The composition of the microbial community in the intestine may influence the functions of distant organs such as the brain, lung, and skin. These microbes can promote disease or have beneficial functions, leading to the hypothesis that microbes in the gut explain the co-occurrence of intestinal and skin diseases. Here, we show that the reverse can occur, and that skin directly alters the gut microbiome. Disruption of the dermis by skin wounding or the digestion of dermal hyaluronan results in increased expression in the colon of the host defense genes Reg3 and Muc2, and skin wounding changes the composition and behavior of intestinal bacteria. Enhanced expression Reg3 and Muc2 is induced in vitro by exposure to hyaluronan released by these skin interventions. The change in the colon microbiome after skin wounding is functionally important as these bacteria penetrate the intestinal epithelium and enhance colitis from dextran sodium sulfate (DSS) as seen by the ability to rescue skin associated DSS colitis with oral antibiotics, in germ-free mice, and fecal microbiome transplantation to unwounded mice from mice with skin wounds. These observations provide direct evidence of a skin-gut axis by demonstrating that damage to the skin disrupts homeostasis in intestinal host defense and alters the gut microbiome.

Autonomous artificial intelligence increases screening and follow-up for diabetic retinopathy in youth: the ACCESS randomized control trial.

Diabetic retinopathy can be prevented with screening and early detection. We hypothesized that autonomous artificial intelligence (AI) diabetic eye exams at the point-of-care would increase diabetic eye exam completion rates in a racially and ethnically diverse youth population. AI for Children's diabetiC Eye ExamS (NCT05131451) is a parallel randomized controlled trial that randomized youth (ages 8-21 years) with type 1 and type 2 diabetes to intervention (autonomous artificial intelligence diabetic eye exam at the point of care), or control (scripted eye care provider referral and education) in an academic pediatric diabetes center. The primary outcome was diabetic eye exam completion rate within 6 months. The secondary outcome was the proportion of participants who completed follow-through with an eye care provider if deemed appropriate. Diabetic eye exam completion rate was significantly higher (100%, 95%CI: 95.5%, 100%) in the intervention group (n = 81) than the control group (n = 83) (22%, 95%CI: 14.2%, 32.4%)(p < 0.001). In the intervention arm, 25/81 participants had an abnormal result, of whom 64% (16/25) completed follow-through with an eye care provider, compared to 22% in the control arm (p < 0.001). Autonomous AI increases diabetic eye exam completion rates in youth with diabetes.

Cenozoic extinction and recolonization in the New Zealand flora: the case of the fleshy-fruited epacrids (Styphelieae, Styphelioideae, Ericaceae).

The origins and evolutionary history of the New Zealand flora has been the subject of much debate. The recent description of Cyathodophyllum novaezelandieae from early Miocene sediments in New Zealand provides possible evidence for the antiquity of the fleshy fruited epacrids (tribe Styphelieae, Ericaceae) in New Zealand. Yet the extant species in this tribe are thought to be very closely related to or conspecific with Australian taxa, suggesting recent trans-Tasman origins. In order to investigate the origins and evolution of the extant New Zealand Styphelieae we produced molecular phylogenetic trees based on sequences of three plastid regions that include representatives of all the genera of the tribe and eight of the ten New Zealand species. We estimated the range of minimum ages of the New Zealand lineages with Bayesian relaxed-clock analyses using different calibration methods and relative dating. We found strong support for each of the eight extant species of New Zealand Styphelieae being a distinct lineage that is nested within an Australian clade. In all except one case the sister is from Tasmania and/or the east coast of mainland Australia; for Acrothamnus colensoi the sister is in New Guinea. Estimated dates indicate that all of the New Zealand lineages diverged from their non-New Zealand sisters within the last 7 Ma. Time discontinuity between the fossil C.novae-zelandiae (20-23 Ma) and the origins of the extant New Zealand lineages (none older than 5 Ma) indicates that the fossil and extant Styphelieae in New Zealand are not related. The relative dating analysis showed that to accept this relationship, it would be necessary to accept that the Styphelieae arose in the early-mid Mesozoic (210-120 Ma), which is starkly at odds with multiple lines of evidence on the age of Ericales and indeed the angiosperms. Therefore, our results do not support the hypothesis that Styphelieae have been continuously present in New Zealand since the early Miocene. Instead they suggest a historical biogeographical scenario in which the lineage to which C. novae-zelandiae belongs went extinct in New Zealand, and the extant New Zealand Styphelieae are derived from Australian lineages that recolonised (presumably by long distance dispersal) no earlier than the late Miocene to Pliocene.

Using adult learning characteristics and the humanities to teach undergraduate healthcare students about social determinants of health.

Authors used an andragogy framework to help undergraduate allied health students better understand social determinants of health (SDOH) using a photo essay assignment. The study examined students' perceptions of SDOH in various communities, description of health outcomes associated with their chosen SDOH, and lessons learned and suggestions to improve the assignment for future cohorts. Data were extracted from photo essays from 2019-2021 and entered in Microsoft Excel and Word for data analysis after course completion. Conventional qualitative content analysis was used to analyze student evaluation data from open-ended questions. Data were extracted from 53 student essays from 2019 to 2021. Most photo essays described communities in South Carolina (n = 42, 79.2%), urban areas (n = 37, 69.8%), or intermediary SDOH (75.5%). Several themes emerged concerning lessons learned (awareness and empathy are key to addressing SDOH), health equity (collaboration is necessary to provide resources, especially for underserved populations), and constructive feedback for the instructor (more time to discuss SDOH and assignment with peers and instructor). Faculty must work with students to think about more upstream factors like policy and cultural and societal values. Collecting evaluation data, specifically lessons learned and constructive feedback for faculty, can help faculty continuously improve course topics and assignments. Following a transparency framework can support student success and help faculty become effective leaders in the classroom while teaching subjects like SDOH and social justice.

Real-World Glycemic Outcomes with Early Omnipod 5 Use in Youth with Type 1 Diabetes.

Background: Pivotal trials of diabetes technologies have demonstrated glycemic improvements; however, these trials include patients of limited diversity and ranges of glycemic control. We assessed changes in glycemic control during the first 90 days of Omnipod 5 use in a real-world cohort of youth with type 1 diabetes (T1D). Methods: Youth 2-21 years with T1D initiating Omnipod 5 at two pediatric academic centers were included. Fourteen days of baseline (BL) continuous glucose monitoring (CGM) data were compared against data from the first 90 days of Omnipod 5 use. Outcome measures included changes in time in range (TIR), hemoglobin A1c (HbA1c), and CGM and insulin pump metrics based on the duration of Omnipod 5 use. Results: Among 195 youth (78.9% non-Hispanic White, 15.4% publicly insured, age 11.7 years, T1D duration 3.3 years) TIR increased 11%-points, from 49% to 61% (P < 0.001), and HbA1c decreased 0.5%-points, from 7.5% to 6.9% (P < 0.001). TIR improved within the first 9 days of Omnipod 5 use (p < 0.001) and did not change significantly thereafter (P = 0.1) despite decreases in user-initiated boluses (5.1 vs. 5.0, P = 0.01) and carbohydrate entries (4.2 vs. 4.1, P = 0.005) from days 1-9 to days 1-90. TIR improved 15%-points among youth with BL TIR <60% compared to a 5%-point increase for youth with BL TIR ≥60% (P < 0.001). Conclusions: Glycemic control improved within 9 days of Omnipod 5 initiation in this real-world cohort, and improvements were sustained over the first 90 days of use despite concomitant decreases in user-initiated boluses. These improvements were comparable to those observed in the pivotal trial.

Short-term use of CGM in youth onset type 2 diabetes is associated with behavioral modifications.

Background: Continuous glucose monitoring (CGM) is beneficial to glycemic control in youth with type 1 diabetes (T1D) and adults with type 2 diabetes (T2D); however, studies in youth with T2D are limited. Objective: Determine if 10-day trial CGM use in youth with T2D improves glycemic control and behavioral modifications. Methods: Youth with T2D > 3 months, on insulin, with no prior CGM use were enrolled. Staff placed CGM and provided education. Participants received 5-day and 10-day follow-up phone calls to review CGM data, behavioral modifications, and adjust insulin doses as needed. We compared 5-day to 10-day TIR, and baseline to 3-6 month HbA1c via paired t-test. Results: Participants (n=41) had median age of 16.2 y, were 61% female, 81% NH Black, median diabetes duration of 0.8 y, and baseline HbA1c of 10.3%. A majority had household income<$50,000 (81%) and parental education level of HS or less (73%). Average 5-day TIR 49% was similar to 10-day TIR 51% (p=0.62). There was no change in HbA1c after 3-6 months (10.2% v 10.3%, p=0.89). Nineteen participants completed full 10-day CGM use; of those, 84% wanted a CGM long-term. Adolescents reported behavioral changes including increased blood sugar checks, increased insulin administration and overall improved diabetes management. Conclusion: Although 10-day CGM use did not impact short-term or long-term glycemic control in youth with T2D, most participants reported behavioral changes and wanted to continue using CGM. Future studies with longer use of CGM may clarify the potential impact of CGM in youth with T2D.

Improving Continuous Glucose Monitoring Uptake in Underserved Youth with Type 1 Diabetes: The IMPACT Study.

Background: Continuous glucose monitoring (CGM) improves glycemic control. Less than half of youth with type 1 diabetes (T1D) use CGM, with disparities among minority and low-income youth. The aim of this study was to determine if trial CGM use increases uptake of personal CGM. Methods: T1D youth were provided sample CGM placement at the point of care, with CGM education and app setup. Follow-up calls at 5 and 10 days assessed CGM data, and desire to continue using CGM. Follow-up at 3-6 months recorded CGM use, CGM data, and A1c. Participants completed surveys at enrollment, 10 days, and 3 months. Differences were assessed between baseline and follow-up. Results: Of the 26 enrolled participants with T1D, 15 were CGM naive, and 11 were prior CGM users. The mean age was 14.1 ± 2.9 years, 65% male, 42% were Black, 12% were Hispanic, 65% were on public insurance, and 43% had household income of <$50,000. The median duration of diabetes was 4.6 years (interquartile range 2.4-7.7), mean baseline A1c was 10.7% ± 2.4%. After trial CGM use, 85% of participants reported wanting personal CGM, and at 3-6 months follow-up 76% had obtained one and 43% were using a personal CGM. There were no improvements in A1C or time in range, but participants reported an increase in the perceived benefits of CGM usage (4.0 vs. 4.3, p = 0.03). Conclusions: Placing a sample CGM at the point of care can improve uptake of personal CGM and may help mitigate disparities in CGM use in minority and underserved youth. Long-term studies are needed to determine how similar interventions impact glycemic control and patient outcomes. ClinicalTrials.gov: NCT04721145.

Effect of pegbelfermin on NASH and fibrosis-related biomarkers and correlation with histological response in the FALCON 1 trial.

Background & Aims: FALCON 1 was a phase IIb study of pegbelfermin in patients with non-alcoholic steatohepatitis (NASH) and stage 3 fibrosis. This FALCON 1 post hoc analysis aimed to further assess the effect of pegbelfermin on NASH-related biomarkers, correlations between histological assessments and non-invasive biomarkers, and concordance between the week 24 histologically assessed primary endpoint response and biomarkers. Methods: Blood-based composite fibrosis scores, blood-based biomarkers, and imaging biomarkers were evaluated for patients with available data from FALCON 1 at baseline through week 24. SomaSignal tests assessed protein signatures of NASH steatosis, inflammation, ballooning, and fibrosis in blood. Linear mixed-effect models were fit for each biomarker. Correlations and concordance were assessed between blood-based biomarkers, imaging, and histological metrics. Results: At week 24, pegbelfermin significantly improved blood-based composite fibrosis scores (ELF, FIB-4, APRI), fibrogenesis biomarkers (PRO-C3 and PC3X), adiponectin, CK-18, hepatic fat fraction measured by MRI-proton density fat fraction, and all four SomaSignal NASH component tests. Correlation analyses between histological and non-invasive measures identified four main categories: steatosis/metabolism, tissue injury, fibrosis, and biopsy-based metrics. Concordant and discordant effects of pegbelfermin on the primary endpoint vs. biomarker responses were observed; the most clear and concordant effects were on measures of liver steatosis and metabolism. A significant association between hepatic fat measured histologically and by imaging was observed in pegbelfermin arms. Conclusions: Pegbelfermin improved NASH-related biomarkers most consistently through improvement of liver steatosis, though biomarkers of tissue injury/inflammation and fibrosis were also improved. Concordance analysis shows that non-invasive assessments of NASH support and exceed the improvements detected by liver biopsy, suggesting that greater consideration should be given to the totality of available data when evaluating the efficacy of NASH therapeutics. Clinical trial number: Post hoc analysis of NCT03486899. Impact and implications: FALCON 1 was a study of pegbelfermin vs. placebo in patients with non-alcoholic steatohepatitis (NASH) without cirrhosis; in this study, patients who responded to pegbelfermin treatment were identified through examination of liver fibrosis in tissue samples collected through biopsy. In the current analysis, non-invasive blood- and imaging-based measures of fibrosis, liver fat, and liver injury were used to determine pegbelfermin treatment response to see how they compared with the biopsy-based results. We found that many of the non-invasive tests, particularly those that measured liver fat, identified patients who responded to pegbelfermin treatment, consistent with the liver biopsy findings. These results suggest that there may be additional value in using data from non-invasive tests, along with liver biopsy, to evaluate how well patients with NASH respond to treatment.