Disentangling fetal insulin hypersecretion and insulin resistance.

Disentangling which of insulin hypersecretion and insulin resistance is upstream in obesity-related type 2 diabetes (T2D) is challenging. Here, we consider the dynamics of insulin secretion and action in the fetuses of mothers with diabetes. We argue that fetal insulin hypersecretion occurs first, with insulin resistance being an adaptive protective response.

Cost-effectiveness of diagnosis and treatment of early gestational diabetes mellitus: economic evaluation of the TOBOGM study, an international multicenter randomized controlled trial.

Background: A recently undertaken multicenter randomized controlled trial (RCT) "Treatment Of BOoking Gestational diabetes Mellitus" (TOBOGM: 2017-2022) found that the diagnosis and treatment of pregnant women with early gestational diabetes mellitus (GDM) improved pregnancy outcomes. Based on data from the trial, this study aimed to assess the cost-effectiveness of diagnosis and treatment of early GDM (from <20 weeks') among women with risk factors for hyperglycemia in pregnancy compared with usual care (no treatment until 24-28 weeks') from a healthcare perspective. Methods: Participants' healthcare resource utilization data were collected from their self-reported questionnaires and hospital records, and valued using the unit costs obtained from standard Australian national sources. Costs were reported in US dollars ($) using the purchasing power parity (PPP) estimates to facilitate comparison of costs across countries. Intention-to-treat (ITT) principle was followed. Missing cost data were replaced using multiple imputations. Bootstrapping method was used to estimate the uncertainty around mean cost difference and cost-effectiveness results. Bootstrapped cost-effect pairs were used to plot the cost-effectiveness (CE) plane and cost-effectiveness acceptability curve (CEAC). Findings: Diagnosis and treatment of early GDM was more effective and tended to be less costly, i.e., dominant (cost-saving) [-5.6% composite adverse pregnancy outcome (95% CI: -10.1%, -1.2%), -$1373 (95% CI: -$3,749, $642)] compared with usual care. Our findings were confirmed by both the CE plane (88% of the bootstrapped cost-effect pairs fall in the south-west quadrant), and CEAC (the probability of the intervention being cost-effective ranged from 84% at a willingness-to-pay (WTP) threshold value of $10,000-99% at a WTP threshold value of $100,000 per composite adverse pregnancy outcome prevented). Sub-group analyses demonstrated that diagnosis and treatment of early GDM among women in the higher glycemic range (fasting blood glucose 95-109 mg/dl [5.3-6.0 mmol/L], 1-h blood glucose ≥191 mg/dl [10.6 mmol/L] and/or 2-h blood glucose 162-199 mg/dl [9.0-11.0 mmol/L]) was more effective and less costly (dominant) [-7.8% composite adverse pregnancy outcome (95% CI: -14.6%, -0.9%), -$2795 (95% CI: -$6,638, -$533)]; the intervention was more effective and tended to be less costly [-8.9% composite adverse pregnancy outcome (95% CI: -15.1%, -2.6%), -$5548 (95% CI: -$16,740, $1547)] among women diagnosed before 14 weeks' gestation as well. Interpretation: Our findings highlight the potential health and economic benefits from the diagnosis and treatment of early GDM among women with risk factors for hyperglycemia in pregnancy and supports its implementation. Long-term follow-up studies are recommended as a key future area of research to assess the potential long-term health benefits and economic consequences of the intervention. Funding: National Health and Medical Research Council (grants 1104231 and 2009326), Region O¨rebro Research Committee (grants Dnr OLL-970566 and OLL-942177), Medical Scientific Fund of the Mayor of Vienna (project 15,205 and project 23,026), South Western Sydney Local Health District Academic Unit (grant 2016), and Western Sydney University Ainsworth Trust Grant (2019).

Expression of Cathepsin D in early-stage breast cancer and its prognostic and predictive value.

PURPOSE: Cathepsin D is a proteolytic enzyme that is normally localized in the lysosomes and is involved in the malignant progression of breast cancer. There are conflicting results regarding Cathepsin D significance as prognostic and predictor marker in breast cancer. This study aimed to evaluate the expression and prognostic significance of Cathepsin D in early-stage breast cancer. METHODS: Expression of Cathepsin D was assessed by immunohistochemical staining of tissue microarrays, in a large well-characterized series of early-stage operable breast cancer (n = 954) from Nottingham Primary Breast Carcinoma Series between the period of 1988 and 1998 who underwent primary surgery. Correlation of Cathepsin D expression with clinicopathological parameters and prognosis was evaluated. RESULTS: Cathepsin D expression was positive in 71.2% (679/954) of breast cancer tumours. Positive expression of Cathepsin D was significantly associated with high histological grade (p = 0.007), pleomorphism (p = 0.002), poor Nottingham Prognostic Index (NPI) score (p < 0.002), recurrence (p = 0.005) and distant metastasis (p < 0.0001). Kaplan-Meier analysis showed that Cathepsin D expression was significantly associated with shorter breast cancer-specific survival (p = 0.001), higher risk of recurrence (p = 0.001) and distant metastasis (p < 0.0001). ER-positive tumours expressing Cathepsin D and treated with tamoxifen demonstrated a significantly higher risk of distant metastasis. CONCLUSION: Cathepsin D expression significantly predicts poor prognosis in breast cancer and is associated with variables of poor prognosis and shorter outcome. The strong association of Cathepsin D with aggressive tumour characteristics and poor outcomes warrants further research of its potential as a therapeutic target The results also suggest a possible interaction between Cathepsin D and tamoxifen therapy in ER-positive breast cancer which needs further investigation to elucidate the underlying mechanisms.

Assessing the influence of dopamine and mindfulness on the formation of routines in visual search.

Given experience in cluttered but stable visual environments, our eye-movements form stereotyped routines that sample task-relevant locations, while not mixing-up routines between similar task-settings. Both dopamine signaling and mindfulness have been posited as factors that influence the formation of such routines, yet quantification of their impact remains to be tested in healthy humans. Over two sessions, participants searched through grids of doors to find hidden targets, using a gaze-contingent display. Within each session, door scenes appeared in either one of two colors, with each color signaling a differing set of likely target locations. We derived measures for how well target locations were learned (target-accuracy), how routine were sets of eye-movements (stereotypy), and the extent of interference between the two scenes (setting-accuracy). Participants completed two sessions, where they were administered either levodopa (dopamine precursor) or placebo (vitamin C), under double-blind counterbalanced conditions. Dopamine and trait mindfulness (assessed by questionnaire) interacted to influence both target-accuracy and stereotypy. Increasing dopamine improved accuracy and reduced stereotypy for high mindfulness scorers, but induced the opposite pattern for low mindfulness scorers. Dopamine also disrupted setting-accuracy invariant to mindfulness. Our findings show that mindfulness modulates the impact of dopamine on the target-accuracy and stereotypy of eye-movement routines, whereas increasing dopamine promotes interference between task-settings, regardless of mindfulness. These findings provide a link between non-human and human models regarding the influence of dopamine on the formation of task-relevant eye-movement routines and provide novel insights into behavior-trait factors that modulate the use of experience when building adaptive repertoires.

Regression From Early GDM to Normal Glucose Tolerance and Adverse Pregnancy Outcomes in the Treatment of Booking Gestational Diabetes Mellitus Study.

OBJECTIVE: To compare pregnancy outcomes among women with a normal oral glucose tolerance test (OGTT) before 20 weeks' gestation (early) and at 24-28 weeks' gestation (late) (no gestational diabetes mellitus, or No-GDM), those with early GDM randomized to observation with a subsequent normal OGTT (GDM-Regression), and those with GDM on both occasions (GDM-Maintained). RESEARCH DESIGN AND METHODS: Women at <20 weeks' gestation with GDM risk factors who were recruited for a randomized controlled early GDM treatment trial were included. Women with treated early GDM and late GDM (according to the World Health Organization's 2013 criteria) were excluded from this analysis. Logistic regression compared pregnancy outcomes. RESULTS: GDM-Regression (n = 121) group risk factor profiles and OGTT results generally fell between the No-GDM (n = 2,218) and GDM-Maintained (n = 254) groups, with adjusted incidences of pregnancy complications similar between the GDM-Regression and No-GDM groups. CONCLUSIONS: Women with early GDM but normal OGTT at 24-28 weeks' gestation had pregnancy outcomes that were similar to those of individuals without GDM. Identifying early GDM likely to regress would allow treatment to be avoided.

Adaptation of sequential action benefits from timing variability related to lateral basal ganglia circuitry.

Streamlined action sequences must remain flexible should stable contingencies in the environment change. By combining analyses of behavioral structure with a circuit-specific manipulation in mice, we report on a relationship between action timing variability and successful adaptation that relates to post-synaptic targets of primary motor cortical (M1) projections to dorsolateral striatum (DLS). In a two-lever instrumental task, mice formed successful action sequences by, first, establishing action scaffolds and, second, smoothly extending action duration to adapt to increased task requirements. Interruption of DLS neurons in M1 projection territories altered this process, evoking higher-rate actions that were more stereotyped in their timing, reducing opportunities for success. Based on evidence from neuronal tracing experiments, we propose that DLS neurons in M1 projection territories supply action timing variability to facilitate adaptation, a function that may involve additional downstream subcortical processing relating to collateralization of descending motor pathways to multiple basal ganglia centers.

Nanowire Array Breath Acetone Sensor for Diabetes Monitoring.

Diabetic ketoacidosis (DKA) is a life-threatening acute complication of diabetes characterized by the accumulation of ketone bodies in the blood. Breath acetone, a ketone, directly correlates with blood ketones. Therefore, monitoring breath acetone can significantly enhance the safety and efficacy of diabetes care. In this work, the design and fabrication of an InP/Pt/chitosan nanowire array-based chemiresistive acetone sensor is reported. By incorporation of chitosan as a surface-functional layer and a Pt Schottky contact for efficient charge transfer processes and photovoltaic effect, self-powered, highly selective acetone sensing is achieved. The sensor has exhibited an ultra-wide acetone detection range from sub-ppb to >100 000 ppm level at room temperature, covering those in the exhaled breath from healthy individuals (300-800 ppb) to people at high risk of DKA (>75 ppm). The nanowire sensor has also been successfully integrated into a handheld breath testing prototype, the Ketowhistle, which can successfully detect different ranges of acetone concentrations in simulated breath samples. The Ketowhistle demonstrates the immediate potential for non-invasive ketone monitoring for people living with diabetes, in particular for DKA prevention.

Perinatal Outcomes in Early and Late Gestational Diabetes Mellitus After Treatment From 24-28 Weeks' Gestation: A TOBOGM Secondary Analysis.

OBJECTIVE: In most gestational diabetes mellitus (GDM) studies, cohorts have included women combined into study populations without regard to whether hyperglycemia was present earlier in pregnancy. In this study we sought to compare perinatal outcomes between groups: women with early GDM (EGDM group: diagnosis before 20 weeks but no treatment until 24-28 weeks if GDM still present), with late GDM (LGDM group: present only at 24-28 weeks), and with normoglycemia at 24-28 weeks (control subjects). RESEARCH DESIGN AND METHODS: This is a secondary analysis of a randomized controlled treatment trial where we studied, among women with risk factors, early (<20 weeks' gestation) GDM defined according to World Health Organization 2013 criteria. Those receiving early treatment for GDM treatment were excluded. GDM was treated if present at 24-28 weeks. The primary outcome was a composite of birth before 37 weeks' gestation, birth weight ≥4,500 g, birth trauma, neonatal respiratory distress, phototherapy, stillbirth/neonatal death, and shoulder dystocia. Comparisons included adjustment for age, ethnicity, BMI, site, smoking, primigravity, and education. RESULTS: Women with EGDM (n = 254) and LGDM (n = 467) had shorter pregnancy duration than control subjects (n = 2,339). BMI was lowest with LGDM. The composite was increased with EGDM (odds ratio [OR] 1.59, 95% CI 1.18-2.12)) but not LGDM (OR 1.19, 95% CI 0.94-1.50). Induction of labor was higher in both GDM groups. In comparisons with control subjects there were higher birth centile, higher preterm birth rate, and higher rate of neonatal jaundice for the EGDM group (but not the LGDM group). The greatest need for insulin and/or metformin was with EGDM. CONCLUSIONS: Adverse perinatal outcomes were increased with EGDM despite treatment from 24-28 weeks' gestation, suggesting the need to initiate treatment early, and more aggressively, to reduce the effects of exposure to the more severe maternal hyperglycemia from early pregnancy.

Pancreas agenesis and fetal growth: a semi-quantitative analysis.

Pancreas agenesis is a rare condition underlying a variant of permanent neonatal diabetes mellitus. Neonates with this condition are born small for gestational age, but less is known about which components of growth are impacted, the timing of the growth restriction and potential sex differences. Our objective was to assess in which periods in gestation complete pancreas agenesis restricts fetal growth and possible sex differences in susceptibility. Published cases (n=49) with pancreas agenesis providing relevant data (gestational age, fetal sex, birth weight, birth length, head circumference, placental weight) were identified by MEDLINE and secondary literature search covering the years 1950-January 2023. Semi-quantitative analysis of these case reports used centiles based on Intergrowth-21 reference charts. Neonates with pancreas agenesis were severely growth restricted, however, median centiles for birth weight, length and head circumference of those born before week 36 were significantly higher compared to those born from 36 weeks. Similar results were found when data were separated by before and from 38 weeks. Head circumference was less affected than birth weight or length. No sex differences were found. In conclusion, pancreas agenesis severely restricts fetal length and head circumference in addition to weight growth, with stronger effects evident from 36 weeks of gestation. In addition to the well-known effects of insulin on growth of fetal fat mass, the pronounced effect on birth length and head circumference indicates effects of insulin on fetal lean body growth as well. Lack of power may account for failure to find sex differences.

Stimulus-outcome associations are required for the expression of specific Pavlovian-instrumental transfer.

A series of experiments employed a specific Pavlovian-instrumental transfer (PIT) task in rats to determine the capacity of various treatments to undermine two outcome-specific stimulus-outcome (S-O) associations. Experiment 1 tested a random treatment, which involved uncorrelated presentations of the two stimuli and their predicted outcomes. This treatment disrupted the capacity of the outcome-specific S-O associations to drive specific PIT. Experiment 2 used a negative-contingency treatment during which the predicted outcomes were exclusively delivered in the absence of their associated stimulus. This treatment spared specific PIT, suggesting that it left the outcome-specific S-O associations relatively intact. The same outcome was obtained in Experiment 3, which implemented a zero-contingency treatment consisting of delivering the predicted outcomes in the presence and absence of their associated stimulus. Experiment 4 tested a mixed treatment, which distributed the predicted outcomes at an equal rate during each stimulus. This treatment disrupted the capacity of the outcome-specific S-O associations to drive specific PIT. We suggest that the mixed treatment disrupted specific PIT by generating new and competing outcome-specific S-O associations. By contrast, we propose that the random treatment disrupted specific PIT by undermining the original outcome-specific S-O associations, indicating that these associations must be retrieved to express specific PIT. We discuss how these findings inform our theoretical understanding of the mechanisms underlying this phenomenon. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The relationship between body mass index and sleep in women with risk factors for gestational diabetes mellitus.

Background: Both obesity and sleep disorders are common among women during pregnancy. Although prior research has identified a relationship between obesity and sleep disorders, those findings are from women later in pregnancy. Objective: To explore the relationships between self-reported sleep duration, insufficient sleep and snoring with body mass index (BMI) among multiethnic women at risk of gestational diabetes mellitus (GDM)in early pregnancy. Methods: Cross-sectional study of baseline data from women at risk of GDM enrolled in the Treatment of BOoking Gestational diabetes Mellitus (TOBOGM) multicentre trial across 12 Australian/Austrian sites. Participants completed a questionnaire before 20 weeks' gestation to evaluate sleep. BMI <25 kg/m2 served as the reference group in multivariable logistic regression. Results: Among the 2865 women included, the prevalence of overweight and obesity classes I-III was 28%, 19%, 11% and 12%, respectively. There was no relationship between sleep duration and BMI. The risk of insufficient sleep >5 days/month was higher in class II and class III obesity (1.38 (1.03-1.85) and 1.34 (1.01-1.80), respectively), and the risk of snoring increased as BMI increased (1.59 (1.25-2.02), 2.68 (2.07-3.48), 4.35 (3.21-5.88) to 4.96 (3.65-6.74), respectively)). Conclusions: Obesity is associated with insufficient sleep among pregnant women at risk of GDM. Snoring is more prevalent with increasing BMI.

Jointly Predicting Postprandial Hypoglycemia and Hyperglycemia Using Continuous Glucose Monitoring Data in Type 1 Diabetes.

The development of continuous glucose monitoring (CGM) systems has enabled people with type 1 diabetes mellitus (T1DM) to track their glucose trajectory in real-time and inspired research in personalised glucose prediction. In this paper, our aim is to predict postprandial abnormal-glycemia events. Different from prior research which focuses on hypoglycemia only, we make the first attempt to establish our problem as the joint prediction of hyperglycemia and hypoglycemia. On this basis, we propose a machine learning model that learns from the pattern of 1 hour past glucose and makes predictions for the two tasks simultaneously using a unified backbone. Key benefits of our methodology include 1) requiring only the CGM sequence as the input, thus making it more widely applicable than other counterparts using extra inputs such as the nutrition details, and 2) minimising the computational cost as the two tasks are unified into a single model. Our experiments on the openly available OhioT1DM dataset achieve state-of-the-art performance (Matthew's correlation coefficient of 0.61 for hyperglycemia and 0.48 for hypoglycemia). To encourage further study, we release our codes at https://github.com/r-cui/PostprandialHyperHypoPrediction under the MIT license.

Wildfires and COVID-19: syndemic impact on maternal and child health.

The prevailing COVID-19 pandemic and climate change-mediated wildfires can combine to impact maternal-child health, yet this connection remains understudied. To shape policies and design interventions to mitigate the combined effects of future global catastrophes, it is vital to holistically evaluate the impact of syndemics on maternal-child health.

Heatwaves and wildfires suffocate our healthy start to life: time to assess impact and take action.

Adverse environmental exposures in utero and early childhood are known to programme long-term health. Climate change, by contributing to severe heatwaves, wildfires, and other natural disasters, is plausibly associated with adverse pregnancy outcomes and an increase in the future burden of chronic diseases in both mothers and their babies. In this Personal View, we highlight the limitations of existing evidence, specifically on the effects of severe heatwave and wildfire events, and compounding syndemic events such as the COVID-19 pandemic, on the short-term and long-term physical and mental health of pregnant women and their babies, taking into account the interactions with individual and community vulnerabilities. We highlight a need for an international, interdisciplinary collaborative effort to systematically study the effects of severe climate-related environmental crises on maternal and child health. This will enable informed changes to public health policy and clinical practice necessary to safeguard the health and wellbeing of current and future generations.

Objective perimetry identifies regional functional progression and recovery in mild Diabetic Macular Oedema.

PURPOSE: Retinal function beyond foveal vision is not routinely examined in the clinical screening and management of diabetic retinopathy although growing evidence suggests it may precede structural changes. In this study we compare optical coherence tomography (OCT) based macular structure with function measured objectively with the ObjectiveFIELD Analyzer (OFA), and with Matrix perimetry. We did that longitudinally in Type 2 diabetes (T2D) patients with mild Diabetic Macular Oedema (DMO) with good vision and a similar number of T2D patients without DMO, to evaluate changes in retinal function more peripherally over the natural course of retinopathy. METHODS: Both eyes of 16 T2D patients (65.0 ± 10.1, 10 females), 10 with baseline DMO, were followed for up longitudinally for 27 months providing 94 data sets. Vasculopathy was assessed by fundus photography. Retinopathy was graded using to Early Treatment of Diabetic Retinopathy Study (ETDRS) guidelines. Posterior-pole OCT quantified a 64-region/eye thickness grid. Retinal function was measured with 10-2 Matrix perimetry, and the FDA-cleared OFA. Two multifocal pupillographic objective perimetry (mfPOP) variants presented 44 stimuli/eye within either the central 30° or 60° of the visual field, providing sensitivities and delays for each test-region. OCT, Matrix and 30° OFA data were mapped to a common 44 region/eye grid allowing change over time to be compared at the same retinal regions. RESULTS: In eyes that presented with DMO at baseline, mean retinal thickness reduced from 237 ± 25 µm to 234.2 ± 26.7 µm, while the initially non-DMO eyes significantly increased their mean thickness from 250.7 ± 24.4 µm to 255.7 ± 20.6 µm (both p<0.05). Eyes that reduced in retinal thickness over time recovered to more normal OFA sensitivities and delays (all p<0.021). Matrix perimetry quantified fewer regions that changed significantly over the 27 months, mostly presenting in the central 8 degrees. CONCLUSIONS: Changes in retinal function measured by OFA possibly offer greater power to monitor DMO over time than Matrix perimetry data.

Treatment of Gestational Diabetes Mellitus Diagnosed Early in Pregnancy.

BACKGROUND: Whether treatment of gestational diabetes before 20 weeks' gestation improves maternal and infant health is unclear. METHODS: We randomly assigned, in a 1:1 ratio, women between 4 weeks' and 19 weeks 6 days' gestation who had a risk factor for hyperglycemia and a diagnosis of gestational diabetes (World Health Organization 2013 criteria) to receive immediate treatment for gestational diabetes or deferred or no treatment, depending on the results of a repeat oral glucose-tolerance test [OGTT] at 24 to 28 weeks' gestation (control). The trial included three primary outcomes: a composite of adverse neonatal outcomes (birth at <37 weeks' gestation, birth trauma, birth weight of ≥4500 g, respiratory distress, phototherapy, stillbirth or neonatal death, or shoulder dystocia), pregnancy-related hypertension (preeclampsia, eclampsia, or gestational hypertension), and neonatal lean body mass. RESULTS: A total of 802 women underwent randomization; 406 were assigned to the immediate-treatment group and 396 to the control group; follow-up data were available for 793 women (98.9%). An initial OGTT was performed at a mean (±SD) gestation of 15.6±2.5 weeks. An adverse neonatal outcome event occurred in 94 of 378 women (24.9%) in the immediate-treatment group and in 113 of 370 women (30.5%) in the control group (adjusted risk difference, -5.6 percentage points; 95% confidence interval [CI], -10.1 to -1.2). Pregnancy-related hypertension occurred in 40 of 378 women (10.6%) in the immediate-treatment group and in 37 of 372 women (9.9%) in the control group (adjusted risk difference, 0.7 percentage points; 95% CI, -1.6 to 2.9). The mean neonatal lean body mass was 2.86 kg in the immediate-treatment group and 2.91 kg in the control group (adjusted mean difference, -0.04 kg; 95% CI, -0.09 to 0.02). No between-group differences were observed with respect to serious adverse events associated with screening and treatment. CONCLUSIONS: Immediate treatment of gestational diabetes before 20 weeks' gestation led to a modestly lower incidence of a composite of adverse neonatal outcomes than no immediate treatment; no material differences were observed for pregnancy-related hypertension or neonatal lean body mass. (Funded by the National Health and Medical Research Council and others; TOBOGM Australian New Zealand Clinical Trials Registry number, ACTRN12616000924459.).

High Dietary Iron in Western Diet-Fed Male Rats Causes Pancreatic Islet Injury and Acute Pancreatitis.

BACKGROUND: High dietary iron has been linked to an increased type 2 diabetes risk. We have previously shown that intrauterine growth restriction (IUGR) and feeding a Western diet (WD) to male Sprague-Dawley rats independently, as well as together, cause pancreatic islet inflammation, fibrosis, and hemosiderosis. OBJECTIVES: To investigate whether iron has a role in the pathogenesis of this inflammatory islet injury caused by IUGR and WD intake. METHODS: Male Sprague-Dawley offspring of bilateral uterine artery ligated (IUGR) and sham-operated (Sham) dams, fostered to nonoperated dams, were fed a WD [45% sucrose, 19.4% protein and 23% fat (w/w)] containing low iron (LI, 20 mg/kg) or high iron (HI, 500 mg/kg) from weaning. Four groups were studied: Sham-LI, Sham-HI, IUGR-LI, and IUGR-HI. Serial measurements of rat body weight, blood glucose, lipids and insulin, an intraperitoneal glucose tolerance test (age 13 wk), and histological analysis of pancreas and liver (age 14 wk) were recorded. The effects of iron, IUGR, and their interaction, on these measurements have been analyzed. RESULTS: WD with HI compared with LI caused an 11% greater weight gain by age 14 wk (P < 0.001), impaired glucose tolerance [AUC for glucose (G-AUC) 17% higher; P < 0.001), acute pancreatitis (17/18, HI; 6/17, LI; P < 0.001), pancreas-associated fat necrosis and saponification (7/18, HI; 0/17 LI; P < 0.01), and a trend to islet fibrotic injury (7/18, HI; 1/17 LI; P = 0.051). Although pancreatic and hepatic steatosis was evident in almost all WD-fed rats, pancreatic and hepatic iron accumulation was prevalent only in HI-fed rats (P < 0.0001 for both), being only mild in the livers. IUGR, independent of dietary iron, also caused impairment in glucose tolerance (G-AUC: 17% higher; P < 0.05). CONCLUSIONS: A postweaning WD containing HI, independent of IUGR, causes acute pancreatitis and islet injury in Sprague-Dawley rats suggesting a role of dietary iron in the development of steatopancreatitis.

Toward Diabetes Device Development That Is Mindful to the Needs of Young People Living With Type 1 Diabetes: A Data- and Theory-Driven Qualitative Study.

BACKGROUND: An important strategy to understand young people's needs regarding technologies for type 1 diabetes mellitus (T1DM) management is to examine their day-to-day experiences with these technologies. OBJECTIVE: This study aimed to examine young people's and their caregivers' experiences with diabetes technologies in an exploratory way and relate the findings to the existing technology acceptance and technology design theories. On the basis of this procedure, we aimed to develop device characteristics that meet young people's needs. METHODS: Overall, 16 in-person and web-based face-to-face interviews were conducted with 7 female and 9 male young people with T1DM (aged between 12 and 17 years) and their parents between December 2019 and July 2020. The participants were recruited through a pediatric diabetes clinic based at Canberra Hospital. Data-driven thematic analysis was performed before theory-driven analysis to incorporate empirical data results into the unified theory of acceptance and use of technology (UTAUT) and value-sensitive design (VSD). We used the COREQ (Consolidated Criteria for Reporting Qualitative Research) checklist for reporting our research procedure and findings. In this paper, we summarize the key device characteristics that meet young people's needs. RESULTS: Summarized interview themes from the data-driven analysis included aspects of self-management, device use, technological characteristics, and feelings associated with device types. In the subsequent theory-driven analysis, the interview themes aligned with all UTAUT and VSD factors except for one (privacy). Privacy concerns or related aspects were not reported throughout the interviews, and none of the participants made any mention of data privacy. Discussions around ideal device characteristics focused on reliability, flexibility, and automated closed loop systems that enable young people with T1DM to lead an independent life and alleviate parental anxiety. However, in line with a previous systematic review by Brew-Sam et al, the analysis showed that reality deviated from these expectations, with inaccuracy problems reported in continuous glucose monitoring devices and technical failures occurring in both continuous glucose monitoring devices and insulin pumps. CONCLUSIONS: Our research highlights the benefits of the transdisciplinary use of exploratory and theory-informed methods for designing improved technologies. Technologies for diabetes self-management require continual advancement to meet the needs and expectations of young people with T1DM and their caregivers. The UTAUT and VSD approaches were found useful as a combined foundation for structuring the findings of our study.