Modelling and assessment of glucose-lactate kinetics in youth with overweight, obesity and metabolic dysfunction-associated steatotic liver disease: A pilot study.

AIM: In this study, we investigated glucose and lactate kinetics during a 75 g oral glucose tolerance test (OGTT) in 23 overweight and obese adolescents and assessed putative differences among participants with and without metabolic dysfunction-associated steatotic liver disease (MASLD). METHODS: We enrolled 23 young people (six girls) with obesity [body mass index 33 (29-37)]. Glucose-lactate kinetics parameters (disposal glucose insulin sensitivity, SID; fraction of glucose converted into lactate, fr; fractional lactate clearance rate, kL) and lactate production rate (LPR) were estimated using the oral glucose-lactate minimal model. MASLD presence was assessed using the proton density fat fraction. We analysed glucose, lactate and LPR time to peak, peak values and area under the curve and evaluated differences using the Wilcoxon test. MASLD and no-MASLD participants were compared using the Mann-Whitney test. Correlations between parameters were assessed using the Spearman correlation coefficient (ρ). We also tested the performance of two (4 or 3 h OGTT) protocols in estimating oral glucose-lactate minimal model and LPR parameters. RESULTS: Glucose peaks 30 min earlier than lactate (p = .0019). This pattern was present in the no-MASLD group (p < .001). LPR peaks 30 min later in the MASLD group (p = .02). LPR and kL were higher in MASLD, suggesting higher glycolysis and lactate utilization. SID and fr correlate significantly (ρ = -0.55, p = .008). SID and fr were also correlated with the body mass index, (ρ = -0.45, p = .04; and ρ = 0.45; p = .03). The protocol duration did not influence the estimates of the parameters. DISCUSSION: Youth with MASLD showed a delayed glucose metabolism, possibly because of greater utilization of the underlying substrates. A 3-h OGTT may be used to assess lactate metabolism effectively.

Comparison of four Fitbit and Jawbone activity monitors with a research-grade ActiGraph accelerometer for estimating physical activity and energy expenditure.

BACKGROUND/AIM: Consumer-based physical activity (PA) monitors have become popular tools to track PA behaviours. Currently, little is known about the validity of the measurements provided by consumer monitors. We aimed to compare measures of steps, energy expenditure (EE) and active minutes of four consumer monitors with one research-grade accelerometer within a semistructured protocol. METHODS: Thirty men and women (18-80 years old) wore Fitbit One (worn at the waist), Fitbit Zip (waist), Fitbit Flex (wrist), Jawbone UP24 (wrist) and one waist-worn research-grade accelerometer (ActiGraph) while participating in an 80 min protocol. A validated EE prediction equation and active minute cut-points were applied to ActiGraph data. Criterion measures were assessed using direct observation (step count) and portable metabolic analyser (EE, active minutes). A repeated measures analysis of variance (ANOVA) was used to compare differences between consumer monitors, ActiGraph, and criterion measures. Similarly, a repeated measures ANOVA was applied to a subgroup of subjects who didn't cycle. RESULTS: Participants took 3321±571 steps, had 28±6 active min and expended 294±56 kcal based on criterion measures. Comparatively, all monitors underestimated steps and EE by 13%-32% (p<0.01); additionally the Fitbit Flex, UP24, and ActiGraph underestimated active minutes by 35%-65% (p<0.05). Underestimations of PA and EE variables were found to be similar in the subgroup analysis. CONCLUSION: Consumer monitors had similar accuracy for PA assessment as the ActiGraph, which suggests that consumer monitors may serve to track personal PA behaviours and EE. However, due to discrepancies among monitors, individuals should be cautious when comparing relative and absolute differences in PA values obtained using different monitors.

Evaluating Parents' Self-Efficacy for Diabetes Management in Pediatric Type 1 Diabetes.

Objective: To examine the factor structure and construct validity of the Maternal Self-Efficacy for Diabetes Management Scale (MSED) in 135 youth ( Mage = 13.50 ± 1.83 years), with type 1 diabetes mellitus. Method: The study used exploratory factor analysis (EFA) to examine the factor structure and correlations to examine relationships among MSED factors and select parent and child diabetes-related health behaviors and outcomes. Results: EFA identified an 11-item three-factor solution (χ 2 (25, n = 133) = 40.22, p < .03, RMSEA = 0.07, CFI = 0.98, TLI = 0.97), with factors corresponding to parents' perceived ability to manage their child's diabetes (MSED-M), problem-solve issues surrounding glycemic control (MSED-P), and teach their child about diabetes care (MSED-T). Correlational analyses revealed significant associations between the MSED-M and MSED-T and parent-reported optimism and youth's diabetes-specific self-efficacy. The MSED-T was also associated with glycated hemoglobin and self-monitoring blood glucose. Conclusions: Results provide preliminary evidence for the reliability and validity of a three-factor solution of the MSED.

A Longitudinal Examination of Hope and Optimism and Their Role in Type 1 Diabetes in Youths.

OBJECTIVES: To test the longitudinal associations between hope and optimism and health outcomes (i.e., HbA1c and self-monitored blood glucose [SMBG]) among youths with Type 1 diabetes mellitus (T1DM) over a 6-month period. METHODS: A total of 110 participants (aged 10-16 years) completed study measures at Time 1, and 81 completed measures at Time 2. Analyses examined hope and optimism as predictors of change in health outcomes, and examined SMBG as a mediator of the relationship between hope and optimism, and HbA1c. RESULTS: Change in hope, but not optimism, was associated with change in SMBG and HbA1c. Change in SMBG mediated the relationship between change in hope and HbA1c, but not between optimism and HbA1c. CONCLUSIONS: It may be beneficial to assess hope in pediatric T1DM patients to identify youths who may be at risk for poor diabetes management, and to test the benefit of hope-based intervention efforts in clinical studies.

Differential Receptor for Advanced Glycation End Products Expression in Preeclamptic, Intrauterine Growth Restricted, and Gestational Diabetic Placentas.

PROBLEM: Receptor for advanced glycation end products (RAGE) is a receptor implicated in the modulation of inflammation. Inflammation has been associated with pregnancy pathologies including preeclampsia (PE), intrauterine growth restriction (IUGR), and gestational diabetes mellitus (GDM). Our objective was to examine placental RAGE expression in PE, IUGR, and GDM complications. METHOD OF STUDY: Human placental tissues were obtained for RAGE determination using Q-PCR, immunohistochemistry, and Western blot. Invasive trophoblast cells were cultured and treated with AGES for RAGE activation studies. RESULTS: Compared to control placenta, we observed: (i) decreased RAGE gene expression during GDM, (ii) increased RAGE protein in the PE placenta, and (iii) decreased RAGE protein in the IUGR placenta. In trophoblast cells exposed AGEs, we observed: (i) decreased trophoblast invasion, (ii) increased c-Jun N-terminal kinases (JNK) and Extracellular signal-regulated kinases (ERK), and (iii) increased TNF-α and IL-1ß secretion. CONCLUSION: We conclude that placental RAGE is activated during PE and that RAGE-mediated inflammation in the trophoblast involves increased pro-inflammatory cytokine secretion.

Cardiomyocyte mitochondrial respiration is reduced by receptor for advanced glycation end-product signaling in a ceramide-dependent manner.

Cigarette smoke exposure is associated with an increased risk of cardiovascular complications. The role of advanced glycation end products (AGEs) is already well established in numerous comorbidities, including cardiomyopathy. Given the role of AGEs and their receptor, RAGE, in activating inflammatory pathways, we sought to determine whether ceramides could be a mediator of RAGE-induced altered heart mitochondrial function. Using an in vitro model, we treated H9C2 cardiomyocytes with the AGE carboxy-methyllysine before mitochondrial respiration assessment. We discovered that mitochondrial respiration was significantly impaired in AGE-treated cells, but not when cotreated with myriocin, an inhibitor of de novo ceramide biosynthesis. Moreover, we exposed wild-type and RAGE knockout mice to secondhand cigarette smoke and found reduced mitochondrial respiration in the left ventricular myocardium from wild-type mice, but RAGE knockout mice were protected from this effect. Finally, conditional overexpression of RAGE in the lungs of transgenic mice elicited a robust increase in left ventricular ceramides in the absence of smoke exposure. Taken together, these findings suggest a RAGE-ceramide axis as an important contributor to AGE-mediated disrupted cardiomyocyte mitochondrial function.

Cigarette smoke increases cardiomyocyte ceramide accumulation and inhibits mitochondrial respiration.

BACKGROUND: Cigarette smoking is a common and lethal worldwide habit, with considerable mortality stemming from its deleterious effects on heart function. While current theories posit altered blood lipids and fibrinogen metabolism as likely mediators, none have explored the role of the sphingolipid ceramide in exacerbating heart function with smoke exposure. Ceramide production is a consequence of cigarette smoke in the lung, and considering ceramide's harmful effects on mitochondrial function, we sought to elucidate the role of ceramide in mediating smoke-induced altered heart mitochondrial respiration. METHODS: Lung cells (A549) were exposed to cigarette smoke extract (CSE) and heart cells (H9C2) were exposed to the lung-cell conditioned medium. Adult male mice were exposed sidestream cigarette smoke for 8 wk with dietary intervention and ceramide inhibition. Ceramides and heart cell or myocardial mitochondrial respiration were determined. RESULTS: Lung cell cultures revealed a robust response to cigarette smoke extract in both production and secretion of ceramides. Heart cells incubated with lung-cell conditioned medium revealed a pronounced inhibition of myocardial mitochondrial respiration, though this effect was mitigated with ceramide inhibition via myriocin. In vivo, heart ceramides increased roughly 600% in adult mice with long-term sidestream cigarette smoke exposure. This resulted in a significant ceramide-dependent reduction in left myocardial mitochondrial respiration, as heart mitochondria from the mice exposed to both smoke and myriocin injections respired normally. CONCLUSIONS: These results suggest ceramide to be an important mediator of altered myocardial mitochondrial function with cigarette smoke exposure. Thus, anti-ceramide therapies might be considered in the future to protect heart mitochondrial function with smoke exposure.

Ceramides mediate cigarette smoke-induced metabolic disruption in mice.

Cigarette smoke exposure increases lung ceramide biosynthesis and alters metabolic function. We hypothesized that ceramides are released from the lung during cigarette smoke exposure and result in elevated skeletal muscle ceramide levels, resulting in insulin resistance and altered mitochondrial respiration. Employing cell and animal models, we explored the effect of cigarette smoke on muscle cell insulin signaling and mitochondrial respiration. Muscle cells were treated with conditioned medium from cigarette smoke extract (CSE)-exposed lung cells, followed by analysis of ceramides and assessment of insulin signaling and mitochondrial function. Mice were exposed to daily cigarette smoke and a high-fat, high-sugar (HFHS) diet with myriocin injections to inhibit ceramide synthesis. Comparisons were conducted between these mice and control animals on standard diets in the absence of smoke exposure and myriocin injections. Muscle cells treated with CSE-exposed conditioned medium were completely unresponsive to insulin stimulation, and mitochondrial respiration was severely blunted. These effects were mitigated when lung cells were treated with the ceramide inhibitor myriocin prior to and during CSE exposure. In mice, daily cigarette smoke exposure and HFHS diet resulted in insulin resistance, which correlated with elevated ceramides. Although myriocin injection was protective against insulin resistance with either smoke or HFHS, it was insufficient to prevent insulin resistance with combined CS and HFHS. However, myriocin injection restored muscle mitochondrial respiration in all treatments. Ceramide inhibition prevents metabolic disruption in muscle cells with smoke exposure and may explain whole body insulin resistance and mitochondrial dysfunction in vivo.

Female prisoners' preferences of collection methods for testing for Chlamydia trachomatis and Neisseria gonorrhoeae infection.

BACKGROUND: There is an increasing reliance on noninvasive techniques to collect specimens for the detection of sexually transmitted infections. The acceptability of these methods among the general population has been explored, but little is known about their acceptability among women confined in prison. GOAL: The goal was to compare female prisoners' preferences for collection of specimens (self-collected vaginal swab specimens, urine collection, or pelvic examination) for detection of Chlamydia trachomatis and Neisseria gonorrhoeae. STUDY DESIGN: A cross-section of inmates in a large federal prison provided urine samples and self-collected vaginal swab specimens. Women then completed a questionnaire regarding the ease of each method and their preferences for future specimen collection. RESULTS: A total of 535 women between the ages of 18 and 52 years (median = 33) participated in the study. More than half of the participants (57%) reported no difference between urine and swab in terms of ease of collection. Approximately 30% of participants said they would prefer to give a swab specimen in the future rather than collect urine (21%), but nearly half of the women expressed no preference for one method over the other. Most participants (60%) expressed a preference for providing a self-collected swab specimen rather than having a pelvic examination (23%), but nearly 17% expressed a preference for one over the other. CONCLUSION: The study population of female federal prisoners expressed no aversion to the self-collection of either vaginal swab or urine specimens for STD testing. A majority of participants expressed a preference for noninvasive techniques rather than a pelvic examination.