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BackgroundSome weight loss medications, including liraglutide 3.0 mg, are thought to facilitate weight loss by improving appetite control. However, no studies have evaluated their long-term appetitive effects.Subjects/methodsThis study examined changes in appetite in a subsample of 113 adults with obesity (76.1% female, 55.8% white, BMI = 38.8 ± 4.8 kg/m2) who participated in a 52-week trial. Participants were randomized to intensive behavioral therapy alone (IBT-alone), IBT with liraglutide 3.0 mg/day (IBT-liraglutide), or IBT-liraglutide combined with a 12-week meal replacement diet (Multi-component). Participants rated their hunger, fullness after meals, liking of meals, and food preoccupation (all as experienced over the past week) using visual analogue scales (0–100 mm). Ratings were completed at baseline and eight subsequent visits over the year.ResultsAt week 52, participants treated by IBT-alone lost 6.2 ± 1.6% of baseline weight, compared with 11.8 ± 1.6% and 12.1 ± 1.5% in the IBT-liraglutide and Multi-component groups, respectively. Compared to IBT-alone, IBT-liraglutide participants reported larger reductions at week 6 in hunger (−0.3 ± 4.2 vs −16.8 ± 4.0 mm, p = .005) and food preoccupation (+0.2 ± 3.7 vs −16.3 ± 3.6 mm, p = .002) and larger increases in fullness (−5.1 ± 3.2 vs +9.8 ± 3.0 mm, p = .001). These significant differences persisted at all assessments through week 24. There were no differences between IBT-alone and IBT-liraglutide in meal liking. IBT-alone and Multi-component participants differed in hunger at week 6, and in food preoccupation at all assessments through week 24. Multi-component participants reported reduced liking of meals relative to the IBT-alone and IBT-liraglutide groups through weeks 40 and 52, respectively. There were no other differences among any groups at week 52.ConclusionsConsistent with short-term studies, IBT-liraglutide participants reported greater improvements in hunger, fullness, and food preoccupation than those assigned to IBT-alone. Differences in appetite persisted for 24 weeks but were not maintained at week 52, despite the relatively greater weight losses in the liraglutide-treated participants at the trial’s end.

Introduction: Intermittent fasting (IF) is becoming increasingly popular as a method of weight management, but it is unknown whether it affects plasticiser intake with resultant changes in glycaemic control in diabetes and vitamin D (VitD) levels; therefore, this study was undertaken in a cohort of control and type-2 diabetic (T2D) subjects during Ramadan time-restricted feeding (TRF). Methods: In T2D subjects (n = 19) and controls (n = 31) undertaking TRF, 24 h urinary levels of phthalate metabolites, bisphenols and serum VitD were determined pre- and post-TRF by liquid chromatography–tandem mass spectrometry (LC-MS/MS). Anthropometric data and glycosylated haemoglobin (HbA1c) were measured. Results: T2D subjects were older (52 versus 36.73 years, p < 0.001), and had higher BMI (36.54 versus 27.67 kg/m2, p < 0.001), body weight (101.77 versus 80.36 kg, p < 0.001), and HbA1c (8.38 versus 5.46%, p < 0.001) compared to controls, while VitD levels did not differ (60.43 versus 63.95 nmol/L, p > 0.05). Post-TRF, HbA1c was unchanged in T2D subjects and there was no difference in weight, BMI or VitD. Increased mono-iso-butyl phthalate (MiBP) in T2D subjects (10 versus 6.1 ng/mL, p = 0.001) and mono-n-butyl phthalate (MnBP) in T2D subjects (37 versus 13 ng/mL, p = 0.018) and controls (8.3 versus 5.4 ng/mL, p = 0.007) were observed post-TRF; however, significance was lost after adjusting for baseline differences in age, BMI, and HbA1c using a general linear model (GLM) repeated-measures ANOVA. Despite having no median differences in DEHP (di-2-ethylhexyl phthalate) metabolites pre- and post-TRF, analyses revealed a significant time × HbA1c interaction for [mono(2-ethyl-5-carboxypentyl) phthalate, MECPP: F(1,42) = 4.79, p = 0.03, mono(2-ethyl-5-hydroxyhexyl) phthalate, MEHHP: F(1,42) = 8.56, p = 0.006, mono(2-ethylhexyl) phthalate, MEHP: F(1,42) = 4.64, p = 0.03 and mono(2-ethyl-5-oxohexyl) phthalate, MEOHP: F(1,42) = 8.19, p = 0.007] and time × group interactions [MEHHP: F(1,42) = 14.27, p < 0.001, MEHP: F(1,42) = 6.35, p = 0.01 and MEOHP: F(1,42) = 10.30, p = 0.003]. Estimated marginal means (adjusted for age, BMI, HbA1c, and VitD) further confirmed higher concentrations of DEHP metabolites [MECPP, MEHHP, MEHP, and MEOHP] in T2D participants over time compared with controls. Additionally, monomethyl phthalate (MMP) trajectories were significantly influenced by the time × group interaction (F(1,42) = 4.28, p = 0.04), with post-TRF elevations observed in T2D subjects. Vitamin D status was observed to modify mono(3-carboxypropyl) phthalate (MCPP) and MEP trajectories over time. Conclusion: Ramadan TRF is associated with changes in plasticiser metabolite levels, with estimated increased levels in T2D subjects versus healthy controls. Metabolite levels were influenced by HbA1c and vitamin D, though BMI was not observed to be a contributing factor.

Background: Plasticisers with endocrine-disrupting potential are ubiquitous and associate with obesity and type-2 diabetes (T2D), with higher levels reported in the Middle East. However, no data exist on plasticiser exposure in Bahrain where T2D affects 15% of the national population. Methods: An observational exploratory study in T2D (n = 60) and controls (n = 96), analysed for 24 h urinary plasticiser levels (liquid chromatography tandem mass spectrometry (LC-MS/MS)). Correlation and generalised linear model (GLM) analyses were employed to examine associations. Results: T2D were older (p < 0.001), had higher body mass index (BMI) (p < 0.001), body weight (p < 0.001) and glycosylated haemoglobin A1c (HbA1c) (p < 0.001). Correlation analysis revealed differences in inter-plasticiser, and plasticiser and biomarker relationships, with loss or reversal in T2D compared to controls. Mono-n-butyl phthalate (MnBP) levels were higher in T2D (p = 0.04); however, regression analysis revealed significant association with age. The GLM analyses demonstrated marked differences in the levels of mono(3-carboxypropyl) phthalate (MCPP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), monoethyl phthalate (MEP) and bisphenol S (BPS), with lower levels in T2D versus controls (B = −3.41, p = 0.01; B = −5.28, p < 0.001; B = −8.94, p < 0.001; B = −6.09, p = 0.006, respectively); however, these contrasts appeared to be substantially confounded by BMI and/or age. Positive influence of age and negative influence of BMI when observed across the full dataset were generally reversed in T2D. Levels were complementary to those previously reported for the Middle East. Conclusions: The study indicates the phthalate levels in Bahrain are elevated though complementary to studies of phthalates in the Middle East; within those levels, the study indicates differential exposure–response relationships with plasticisers, influenced by age and BMI, in those with T2D compared to healthy controls.

Background Case-based learning (CBL) is a useful pedagogical approach, for which learner experience has been well researched. The experience of faculty is less known. CBL was integrated into the first year of a new pre-licensure medical curriculum, so the faculty experience of transition from large group teaching to structured CBL was investigated. Methodology Interpretative phenomenological analysis (IPA) was undertaken to explore the facilitator lived experience through reflective inquiry. Ten CBL facilitators were purposively selected from a diverse pool of faculty using maximum variation; faculty were involved in patient care, research, and education, and were a mix of ages, ethnicities and genders. Semi-structured interviews were conducted and analysed according to the IPA structure. Results Overall experiences were positive. Facilitators repeatedly expressed the enjoyment felt from closer student interaction. They reported that CBL afforded an authentic and active teaching approach. Other themes included: initial uncertainty regarding their role, anxiety around standardisation of the student experience and concerns regarding the level of content expertise required. However, confidence generally improved with experience facilitating. Conclusion These insights provide a deeper understanding of faculty perceptions of the CBL facilitator’s role and will better inform future faculty development initiatives, as well as the iterative design of the CBL teaching resources.

To explore factors influencing the clinical decision-making of physicians treating patients with type 2 diabetes (T2D) and high risk of atherosclerotic cardiovascular disease (ASCVD) across seven Middle Eastern and African countries. Cross-sectional, anonymous online study of self-reported factors driving clinical decision-making for the management of T2D based on agreement with statements using a five-point Likert scale among physicians (n = 385) in Bahrain, Egypt, Jordan, Kuwait, Qatar, South Africa, and UAE between June 13 and October 1, 2022. From a selection of patient factors, physicians were most likely to agree that treatment adherence/compliance (92%), safety concerns (92%), and impact on health-related quality of life (88%) influenced their decision-making. Most physicians agreed that availability of treatment (87%) was a practice setting factor that influenced their decision-making. The top three physician factors influencing clinical decision-making included continuous medical education (96%), medical knowledge (96%), and international clinical guidelines (95%). Most physicians agreed that improved communication skills of physicians (97%), coaching and question prompts for patients (91%), and patient decision aids (87%) could improve shared decision-making. Various patient, practice, and physician factors influenced physicians' management of their patients with T2D. Physicians believed improving their communication skills could improve shared decision-making. The trial is registered with clinicaltrails.gov, Identifier #NCT05317845 (2023-03-28).

[Please see PDF for full article text] [Please see PDF for full article text] Objectives: To provide insights into the real-world usage of glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) among individuals with type 2 diabetes (T2D) from Bahrain, Kuwait, and Qatar who either had established atherosclerotic cardiovascular disease (eASCVD) or were at high risk of developing ASCVD. Methods: This study of 1062 adults diagnosed with T2D from Bahrain, Kuwait, and Qatar is a sub-analysis within the Prevalence and Clinical Management of Atherosclerotic Cardiovascular Diseases in Patients with Type 2 Diabetes across Countries in the Middle East and Africa (PACT-MEA) study, a noninterventional, cross-sectional study. Participants were recruited from 13 primary or secondary care facilities between March and August 2022. Medical records of participants were reviewed to extract relevant data, including demographic characteristics, eASCVD status, ASCVD risk and glucose-lowering treatment. Appropriate descriptive and inferential statistical tests were performed. Results: Among T2D participants with eASCVD, a significantly higher proportion (41.3%) received SGLT2i compared to GLP-1RA (10.5%, p<0.001). There were notable variations in GLP-1RA/SGLT2i utilization across countries (p<0.001): being lowest in Bahrain (2.3%/18.0%), 26.9%/58.2% in Kuwait and 10.5%/67.1% in Qatar. The use of both medications was significantly higher in individuals with body mass index (BMI) [greater than or equal to]30 kg/[m.sup.2] (p<0.05). Conclusion: Despite these cardioprotective agents being recommended by guidelines, the study findings suggest a suboptimal use of GLP-1RA and SGLT2i in a real-world setting. Keywords: Diabetes mellitus, type 2, atherosclerosis, cardiovascular diseases, hypoglycemic agents, Middle East

Background Patients with diabetic ketoacidosis (DKA), a potentially fatal complication of type 1 diabetes, have hyperglycemia, ketonemia and metabolic acidosis. Blood glucose and blood ketone results are often used to triage patients with suspected DKA. This study aimed to establish how effective blood glucose and blood ketone (beta-hydroxybutyrate, BOHB) measurements are in identifying patients with significant acidosis and sought to validate existing diagnostic BOHB thresholds. Methods Initial Emergency Department results on 161 presumptive DKA episodes in 95 patients (42 F, 53 M, age range 14–89 years) containing a complete dataset of D (glucose), K (BOHB) and A (Bicarbonate [HCO 3 ] and pH) results. Results Blood glucose correlated poorly with BOHB (r = 0.28 p = 0.0003), pH (r= -0.25, p = 0.002) and HCO 3 (r= -0.17, p = 0.04). BOHB, though better, was still limited in predicting pH (r = -0.44, p < 0.0001) and HCO 3 (r = -0.49, p < 0.0001). A HCO 3 of 18mmol/L equated to a BOHB concentration of 4.3mmol/L, whilst a HCO 3 of 15mmol/L equated to a BOHB of 4.7mmol/L. Of the 133 of 161 events with HCO 3  < 18mmol/L, 22 were not hyperglycemic (> 13.9mmol/L, n = 8), ketonemic (≤ 3mmol/L, n = 9) or either (n = 5). Conclusions The commonly employed BOHB diagnostic cutoff of 3mmol/L could not be verified. Since acid-base status was poorly predicted by both glucose and BOHB, this highlights that, regardless of their results, pH and/or HCO 3 should also be tested in any patient suspected of DKA.

The clinical use of niacin to treat dyslipidemic conditions is limited by noxious side effects, most commonly facial flushing. In mice, niacin-induced flushing results from COX-1–dependent formation of PGD2 and PGE2 followed by COX-2–dependent production of PGE2. Consistent with this, niacin-induced flushing in humans is attenuated when niacin is combined with an antagonist of the PGD2 receptor DP1. NSAID-mediated suppression of COX-2–derived PGI2 has negative cardiovascular consequences, yet little is known about the cardiovascular biology of PGD2. Here, we show that PGD2 biosynthesis is augmented during platelet activation in humans and, although vascular expression of DP1 is conserved between humans and mice, platelet DP1 is not present in mice. Despite this, DP1 deletion in mice augmented aneurysm formation and the hypertensive response to Ang II and accelerated atherogenesis and thrombogenesis. Furthermore, COX inhibitors in humans, as well as platelet depletion, COX-1 knockdown, and COX-2 deletion in mice, revealed that niacin evoked platelet COX-1–derived PGD2 biosynthesis. Finally, ADP-induced spreading on fibrinogen was augmented by niacin in washed human platelets, coincident with increased thromboxane (Tx) formation. However, in platelet-rich plasma, where formation of both Tx and PGD2 was increased, spreading was not as pronounced and was inhibited by DP1 activation. Thus, PGD2, like PGI2, may function as a homeostatic response to thrombogenic and hypertensive stimuli and may have particular relevance as a constraint on platelets during niacin therapy.

Background/Aims: Sociocultural and familial factors associated with weight bias internalization (WBI) are currently unknown. The present study explored the relationship between interpersonal sources of weight stigma, family weight history, and WBI. Methods: Participants with obesity (N = 178, 87.6% female, 71.3% black) completed questionnaires that assessed the frequency with which they experienced weight stigma from various interpersonal sources. Participants also reported the weight status of their family members and completed measures of WBI, depression, and demographics. Participant height and weight were measured to calculate body mass index (BMI). Results: Linear regression results (controlling for demographics, BMI, and depression) showed that stigmatizing experiences from family and work predicted greater WBI. Experiencing weight stigma at work was associated with WBI above and beyond the effects of other sources of stigma. Participants who reported higher BMIs for their mothers had lower levels of WBI. Conclusion: Experiencing weight stigma from family and at work may heighten WBI, while having a mother with a higher BMI may be a protective factor against WBI. Prospective research is needed to understand WBI's developmental course and identify mechanisms that increase or mitigate its risk.

Background Vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB) produce substantial weight loss, both primarily through gastric restriction but with potentially different hormonal signaling. This prospective, observational study compared changes in gut-derived hormones in VSG, RYGB, and weight-stable participants at 6 and 18 months post-surgery. Methods Sixty-four obese, non-diabetic women, including 18 VSG, 23 RYGB, and 23 weight-stable controls completed assessments at baseline and 6 months, before and after consuming a mixed-nutrient meal; blood sampling occurred for 180 min post-meal. Fifty-one participants completed the 18-month outcome. Change from baseline in post-prandial area under the curve (over 180 min) for GLP-1, PYY 3–36 , ghrelin, and leptin was measured at 6 and 18 months post-surgery. Results At 18 months, VSG and RYGB participants lost a mean (±SEM) of 25.5 ± 2.3% and 34.2 ± 4.2% of initial weight, respectively ( p  < 0.156), which both differed ( p  < 0.001) from the +1.7 ± 1.0% gain in the control group. Fasting ghrelin declined significantly more in VSG than RYGB participants at both months 6 ( p  = 0.0199) and 18 ( p  = 0.0003). In response to the mixed-nutrient meal, GLP-1 and PYY 3–36 demonstrated an exaggerated post-prandial response that was significantly greater in RYGB than VSG at 6 months ( p  < 0.0001 and p  = 0.0062, respectively) but not 18 months ( p  = 0.0296 and p  = 0.1210). Conclusions VSG and RYGB both produced substantial weight losses at 18 months. The data suggest a role of gastrointestinal hormones as mediators of weight loss.