Weight-matched Controls Research Articles

Preliminary evaluation of ionized magnesium levels in dogs on long-term esomeprazole administration.

To investigate the level of whole-blood ionized magnesium (iMg) in dogs with long-term use of proton pump inhibitors (PPIs). The study included 10 client-owned dogs with esomeprazole administration over 6 months and 62 healthy dogs to determine de novo reference interval (RI) of iMg. Dogs that received esomeprazole for 6 months or longer were retrospectively reviewed to determine the incidence of hypo- or hypermagnesemia based on the de novo RI. Additionally, the iMg levels from the study group were compared with those of 20 age-, sex-, and body weight-matched controls from the 62 dogs. The median (range) duration of esomeprazole usage was 26 months (6 to 94). The de novo RI for iMg was determined as 0.73 (90% CI, 0.58 to 0.87) to 1.43 mg/dL (90% CI, 1.33 to 1.46). Based on the RI, none of the dogs with long-term esomeprazole developed hypo- or hypermagnesemia. The iMg from the matched control group was 1.17 mg/dL (90% CI, 0.83 to 1.46). The lowest iMg after 6 months of esomeprazole administration (90% CI, 0.96 mg/dL, 0.87 to 1.41) was significantly lower than the control group (P = .031). The iMg measured at the end of long-term esomeprazole treatment was 1.03 mg/dL (90% CI, 0.87 to 1.41) and not significantly different from the control group (P = .179). Ionized hypomagnesemia was not observed after long-term use of esomeprazole in the small number of dogs included in this study. Robust RI needs to be determined in future studies to investigate the incidence of hypomagnesemia in dogs with long-term use of PPIs. Future studies in a larger number of dogs are warranted to confirm the findings from the present study and to determine whether the long-term use of esomeprazole in dogs is at risk of developing ionized hypomagnesemia.

Reward and Inhibitory Control as Mechanisms and Treatment Targets for Binge Eating Disorder.

Recent research has highlighted alterations in reward and inhibitory control among individuals with binge eating disorder, identifying both constructs as potential targets for treatment. Treatments targeting reward and inhibitory control for binge eating disorder are emerging. This review aims to summarize the recent literature evaluating reward and inhibitory control in binge eating disorder compared to weight-matched controls using behavioral paradigms and neuroimaging. This review also aims to summarize recent literature evaluating treatments for binge eating targeting these mechanisms and highlights additional work needed in these areas. Reward hypersensitivity and impaired inhibitory control are mechanisms underlying binge eating disorder. Individuals with binge eating disorder experience higher initial reward to food, and later, higher anticipatory reward but lower experienced food reward which maintains binge eating behavior. Treatments targeting reward and inhibitory control for binge eating include behavioral, computerized trainings, pharmacological, and neuromodulation treatments. The majority of trials are small but demonstrate promise in reducing binge eating and targeting theorized mechanisms. Larger, randomized trials are needed. Changes in reward and inhibitory control are present in individuals with binge eating disorder and treatments targeting these mechanisms demonstrate initial promise. Greater research is needed evaluating reward and inhibitory control simultaneously and with weight-matched comparison groups, as well as larger randomized trials that target both processes simultaneously.

Lymphatic morphology and function in chronic right heart failure due to secondary tricuspid valve regurgitation

BackgroundIn heart failure, the capacity of the lymphatic system dictates symptoms of circulatory congestion. This study aimed at describing structural and functional changes of the lymphatic system in patients with chronic right-sided heart failure. MethodsIndividuals with long-standing severe tricuspid valve regurgitation and symptoms of heart failure were compared with age- gender- and weight-matched controls. Lymphatic structure and function were examined using non-contrast MR lymphangiography and near-infrared fluorescence imaging. Microvascular fluid dynamics and distribution were evaluated using strain gauge plethysmography and bio-impedance. ResultsIn total nine patients and nine controls were included. Lymphatic morphology was unchanged in cases compared to controls with similar thoracic duct diameters 3.1(2.1–3.5) mm vs. 2.0(1.8–2.4) mm (p-value = 0.11), similar lymphatic classifications (p-value 0.34), and an identical number of lymphatic vessels in the legs 6 ± 1 vs. 6 ± 3 vessels/field (p-value = 0.72). Lymphatic function was comparable with contraction frequencies of 0.5 ± 0.2 and 0.5 ± 0.3 /min (p-value = 0.52) and a maximal lymphatic pumping pressure of 60 ± 13 and 57 ± 12 mmHg (p-value = 0.59) for cases and controls respectively. Finally, microvascular capillary filtration, isovolumetric threshold, and fluid distribution were similar between groups (p-value≥0.16 for all comparisons). ConclusionIn this small exploratory study, individuals with severe secondary tricuspid valve regurgitation and right-sided heart failure displayed a largely similar lymphatic anatomy and function. Thoracic duct diameter displayed a trend towards increased size in the patient group. We speculate that cases were indeed stable and optimally treated at the time of examination, and with a lymphatic system largely unaffected by any of the current or prior hemodynamic changes.

Acute Exercise Increases GDF15 and Unfolded Protein Response/Integrated Stress Response in Muscle in Type 2 Diabetes.

Regular exercise is a key prevention strategy for obesity and type 2 diabetes (T2D). Exerkines secreted in response to exercise or recovery may contribute to improved systemic metabolism. Conversely, an impaired exerkine response to exercise and recovery may contribute to cardiometabolic diseases. We investigated if the exercise-induced regulation of the exerkine, growth differentiation factor 15 (GDF15) and its putative upstream regulators of the unfolded protein response (UPR)/integrated stress response (ISR) is impaired in skeletal muscle in patients with T2D compared with weight-matched glucose-tolerant men. Thirteen male patients with T2D and 14 age- and weight-matched overweight/obese glucose-tolerant men exercised at 70% of VO2max for 1 hour. Blood and skeletal muscle biopsies were sampled before, immediately after, and 3 hours into recovery. Serum and muscle transcript levels of GDF15 and key markers of UPR/ISR were determined. Additionally, protein/phosphorylation levels of key regulators in UPR/ISR were investigated. Acute exercise increased muscle gene expression and serum GDF15 levels in both groups. In recovery, muscle expression of GDF15 decreased toward baseline, whereas serum GDF15 remained elevated. In both groups, acute exercise increased the expression of UPR/ISR markers, including ATF4, CHOP, EIF2K3 (encoding PERK), and PPP1R15A (encoding GADD34), of which only CHOP remained elevated 3 hours into recovery. Downstream molecules of the UPR/ISR including XBP1-U, XBP1-S, and EDEM1 were increased with exercise and 3 hours into recovery in both groups. The phosphorylation levels of eIF2α-Ser51, a common marker of unfolded protein response (UPR) and ISR, increased immediately after exercise in controls, but decreased 3 hours into recovery in both groups. In conclusion, exercise-induced regulation of GDF15 and key markers of UPR/ISR are not compromised in patients with T2D compared with weight-matched controls.

An extended minimal model of OGTT: estimation of α- and β-cell dysfunction, insulin resistance, and the incretin effect.

Loss of insulin sensitivity, α- and β-cell dysfunction, and impairment in incretin effect have all been implicated in the pathophysiology of type 2 diabetes (T2D). Parsimonious mathematical models are useful in quantifying parameters related to the pathophysiology of T2D. Here, we extend the minimum model developed to describe the glucose-insulin-glucagon dynamics in the isoglycemic intravenous glucose infusion (IIGI) experiment to the oral glucose tolerance test (OGTT). The extended model describes glucose and hormone dynamics in OGTT including the contribution of the incretin hormones, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-1 (GLP-1), to insulin secretion. A new function describing glucose arrival from the gut is introduced. The model is fitted to OGTT data from eight individuals with T2D and eight weight-matched controls (CS) without diabetes to obtain parameters related to insulin sensitivity, β- and α-cell function. The parameters, i.e., measures of insulin sensitivity, a1, suppression of glucagon secretion, k1, magnitude of glucagon secretion, γ2, and incretin-dependent insulin secretion, γ3, were found to be different between CS and T2D with P values < 0.002, <0.017, <0.009, <0.004, respectively. A new rubric for estimating the incretin effect directly from modeling the OGTT is presented. The average incretin effect correlated well with the experimentally determined incretin effect with a Spearman rank test correlation coefficient of 0.67 (P < 0.012). The average incretin effect was found to be different between CS and T2D (P < 0.032). The developed model is shown to be effective in quantifying the factors relevant to T2D pathophysiology.NEW & NOTEWORTHY A new extended model of oral glucose tolerance test (OGTT) has been developed that includes glucagon dynamics and incretin contribution to insulin secretion. The model allows the estimation of parameters related to α- and β-cell dysfunction, insulin sensitivity, and incretin action. A new function describing the influx of glucose from the gut has been introduced. A new rubric for estimating the incretin effect directly from the OGTT experiment has been developed. The effect of glucose dose was also investigated.

Glucagon-like peptide-1 receptor activation stimulates PKA-mediated phosphorylation of Raptor and this contributes to the weight loss effect of liraglutide.

The canonical target of the glucagon-like peptide-1 receptor (GLP-1R), Protein Kinase A (PKA), has been shown to stimulate mechanistic Target of Rapamycin Complex 1 (mTORC1) by phosphorylating the mTOR-regulating protein Raptor at Ser791 following β-adrenergic stimulation. The objective of these studies is to test whether GLP-1R agonists similarly stimulate mTORC1 via PKA phosphorylation of Raptor at Ser791 and whether this contributes to the weight loss effect of the therapeutic GLP-1R agonist liraglutide. We measured phosphorylation of the mTORC1 signaling target ribosomal protein S6 in Chinese Hamster Ovary cells expressing GLP-1R (CHO-Glp1r) treated with liraglutide in combination with PKA inhibitors. We also assessed liraglutide-mediated phosphorylation of the PKA substrate RRXS*/T* motif in CHO-Glp1r cells expressing Myc-tagged wild-type (WT) Raptor or a PKA-resistant (Ser791Ala) Raptor mutant. Finally, we measured the body weight response to liraglutide in WT mice and mice with a targeted knock-in of PKA-resistant Ser791Ala Raptor. Liraglutide increased phosphorylation of S6 and the PKA motif in WT Raptor in a PKA-dependent manner but failed to stimulate phosphorylation of the PKA motif in Ser791Ala Raptor in CHO-Glp1r cells. Lean Ser791Ala Raptor knock-in mice were resistant to liraglutide-induced weight loss but not setmelanotide-induced (melanocortin-4 receptor-dependent) weight loss. Diet-induced obese Ser791Ala Raptor knock-in mice were not resistant to liraglutide-induced weight loss; however, there was weight-dependent variation such that there was a tendency for obese Ser791Ala Raptor knock-in mice of lower relative body weight to be resistant to liraglutide-induced weight loss compared to weight-matched controls. Together, these findings suggest that PKA-mediated phosphorylation of Raptor at Ser791 contributes to liraglutide-induced weight loss.

OR34-03 Defining Clinical Characteristics Of Patients With Severe Hypoglycemia After Roux-en-Y Gastric Bypass: How Do They Differ From Asymptomatic Patients?

Abstract Disclosure: A. Grover: None. A.L. Sheehan: None. C. Cummings: None. M. Farahmandsadr: None. H. Saeed: None. A.M. Puleio: None. D.C. Simonson: Stock Owner; Self; Phase V Technologies, GI Windows. M. Patti: Consulting Fee; Self; AstraZeneca, MBX-Biosciences, Hanmi Pharmaceutical. Other; Self; DSMB: Fractyl Health, Inc. Introduction: Post-bariatric hypoglycemia (PBH) is a severe, disabling complication of Roux-en-Y gastric bypass (RYGB). We aimed to identify clinical characteristics distinguishing patients with severe PBH vs. post-RYGB patients without symptomatic hypoglycemia (RYGB non-hypo) to help elucidate PBH pathophysiology and potential risk factors. Methods: Adults aged 18-70, without diabetes mellitus (DM), were recruited into 3 groups: (1) PBH with neuroglycopenia (n=33); (2) RYGB non-hypo (n=16); (3) non-surgical weight-matched controls (n=17). Detailed history of hypoglycemia, medical/surgical/family history, medications, Dumping Symptom Rating Scale (DSRS), and Rome IV diagnostic criteria for Irritable Bowel Syndrome (IBS) was completed. Differences between PBH and RYGB non-hypo were evaluated by unpaired t-tests and chi-square analysis as indicated. Results: PBH participants were 90% female, mean age 53±2 y, BMI 32±1 kg/m2, 39±2% body fat, with similar data for RYGB non-hypo (100% female, age 54±2 y, BMI 33±2 kg/m2, 40±2% fat), and controls (65% female, age 45±4 y, BMI 31±2 kg/m2, 35±3% fat). 90% of PBH reported level 3 hypoglycemia, with ER visits in 29% and motor vehicle accidents in 7%. Reduced awareness of hypoglycemia was reported by 80% of PBH, with hypoglycemia awareness at mean glucose of 57±2 mg/dL. 29% of PBH reported hypoglycemic symptoms occurring preoperatively, and 20% reported family history of hypoglycemia. The majority of PBH reported depression, change in driving habits, and adverse impact on employment. When compared with RYGB non-hypo, PBH participants had no difference in postoperative weight loss trajectories but had higher prevalence of revisional surgeries (p&amp;lt;0.05). PBH participants also had a higher score on DSRS (p&amp;lt;0.05) and higher prevalence of IBS (48 vs. 7% meeting Rome IV criteria, p&amp;lt;0.05). Higher rates of orthostatic hypotension, intestinal dysmotility, and vitamin B12 deficiency requiring treatment were reported by PBH (p&amp;lt;0.05 for all). Additionally, PBH participants reported greater gabapentin, PPI, and hormonal contraceptive use (p&amp;lt;0.05 for all); there were no differences in SSRI/SNRI use. Conclusion: PBH participants reported high rates of hypoglycemia unawareness, a likely contributor to hypoglycemia severity, recurrence, and adverse effects on safety and personal life. High rates of IBS, dumping symptoms, and orthostatic hypotension suggest possible disordered autonomic regulation in the pathophysiology of PBH. Self-reported preoperative symptoms and family history of hypoglycemia suggest possible differences in glucose metabolism prior to surgery in at-risk individuals. Preoperative assessment of these and other factors, together with longitudinal follow-up studies to determine incidence of PBH, will be required to identify risk factors for development of post-bariatric hypoglycemia. Presentation: Sunday, June 18, 2023

Plasma anti-myosin autoantibodies in the diagnosis of necrotizing enterocolitis

We aimed to assess whether autoantibodies can be used as biomarkers for necrotizing enterocolitis (NEC) and applied for its early diagnosis. A prospective observational study was conducted in neonates with suspected NEC abdominal distension (the developmental study), which consisted of 50 neonates finally divided into NEC (n = 24) and non-NEC (n = 26) cohorts based on follow-up results. Serum samples were collected within 48 h of illness onset and used for screening NEC-associated plasma autoantibodies by autoantigen microarray. Additionally, we validated anti-myosin autoantibodies by enzyme-linked immunosorbent assay (ELISA) in an independent validation study, for which we selected plasma samples within 48 h of onset of NEC (n = 38) and samples of gestational age- and weight-matched controls (n = 13). Autoantigen microarray revealed that both IgG and IgM anti-myosin autoantibodies in plasma from neonates with NEC were significantly higher than those in neonates with other diagnoses. ELISA showed that plasma anti-myosin autoantibodies increased in the NEC cohort, with 1.5-fold higher levels than in the non-NEC cohort. Anti-myosin autoantibodies were able to distinguish NEC from non-NEC, achieving an area under the curve (AUC) of 0.8856 (95% confidence interval (CI): 0.7918–0.9795), with sensitivity of 81.58% and specificity of 76.93%. Plasma anti-myosin autoantibodies were significantly higher in all three subtypes of NEC (P < 0.0001 for NEC I; P = 0.0018 for NEC II; P = 0.0011 for NEC III), especially in NEC stage I than that in the non-NEC controls.Conclusion: Anti-myosin autoantibodies may be applied as a promising diagnostic marker for NEC, especially for NEC stage I.What is Known:• Intestinal damage and self-antigen exposure may lead to increased autoantibodies, and they are widely used as biomarkers for diagnosing inflammatory bowel disease.• Necrotizing enterocolitis (NEC) is a devastating disease with overwhelming inflammation and immune dysregulation.What is New:• Increased autoantibodies were present in patients with NEC, even before typical X-ray manifestations.• Anti-myosin autoantibodies may be applied as a promising diagnostic marker for NEC.

A Case-Control Study of the Carotid Intima Media Thickness as a Good Predictor of Subclinical Atherosclerosis in South Indian Women Diagnosed With Polycystic Ovarian Syndrome in a Tertiary Care Hospital

Background and Objective: Polycystic ovarian syndrome (PCOS) is a diverse condition whose likelihood of heightened cardiovascular disease (CVD) risk in the future is often disregarded. We need to predict the risk sooner due to the intrinsic propensity for CVD in Indians, increased prevalence in South Indians, and PCOS patients. The objectives are: 1. To elicit the presence of CVD risk factor in pcos patients 2. Considering CIMT (Carotid Intima Media Thickness) as a good predictor for CVD risk Methods: A total of 50 cases and 50 age and weight (+/-2 kg) matched controls were included in this study. We assessed the CIMT by the Doppler system with electrical linear transducer midfrequency of 10 MHz. Results: Women with PCOS had a greater CIMT (0.05 ± 0.01 cm in cases vs. 0.03 ± 0 cm in controls; p &lt; 0.001). The CIMT of the cases is increased over their controls by 42.4% (014mm), P ≤0.001. The r value of age and CIMT is more when compared to the r value of weight and CIMT in both cases and controls (Age and CIMT: cases: r= 0.431 &amp; controls: r =0.312) (Weight and CIMT: cases: r = 0.164 &amp; controls: r =0.233). Conclusion: In PCOS , CIMT is a good indicator of CVD risk. When opposed to an individual's weight, age shows a stronger positive correlation with CIMT. Hence, PCOS patients must get an early CIMT scan. CIMT must be a crucial component of PCOS management and CVD risk alleviation.

Outcomes of laparoscopic gastrostomy in children with and without the use of a modified T-fastener technique

BackgroundLaparoscopic gastrostomy is commonly performed for durable enteral access in children. T-fasteners have been used intraoperatively to achieve a secure gastropexy, traditionally using external bolsters. We compare the safety profile of a modified paired T-fastener technique to standard laparoscopic-assisted suture gastropexy. MethodsA retrospective matched case-control study was performed of pediatric patients who underwent laparoscopic gastrostomy at a single center from 2015 to 2021. In the paired T-fastener group, pairs of T-fasteners were passed into the stomach in a square configuration, allowing the suture pairs to be tied subcutaneously. This cohort was matched in a 1:2 fashion with age, sex, and body mass index or weight-matched controls who underwent laparoscopic gastrostomy with buried transabdominal gastropexy. ResultsThirty patients underwent laparoscopic gastrostomy using the paired T-fastener technique and were matched to 60 controls. There was no significant difference in median operative time or 30-day complication rates between the groups, but the paired T-fastener technique significantly reduced the number of trocars required, and it was used for patients with thicker abdominal walls. ConclusionWe demonstrate the modified paired T-fastener technique as a safe, efficient means of gastropexy in pediatric laparoscopic gastrostomy. The paired T-fastener approach eliminates external bolsters, reduces additional trocars, and may be advantageous for thicker abdominal walls while maintaining a similar complication profile to standard laparoscopic gastrostomy.

1630-P: Reduced Fatty Acid Oxidation Does Not Prevent Intralipid-Induced Peripheral Insulin Resistance in Humans

Mitochondrial handling of excess lipid substrate is thought to be an important determinant of insulin resistance. Evidence from animal models support insulin signaling defects resulting from either intra-cellular lipid accumulation or by mitochondrial dysfunction and altered fatty acid oxidation (FAO) flux. To explore the relationship between FAO and insulin sensitivity, we measured the change in peripheral glucose disposal (Rd) during a 5-hour hyperinsulinemic euglycemic clamp with co-infusion of a control glycerol solution versus a 20% intralipid solution in 18 subjects with an inherited defect in FAO (FAOD; including Carnitine Palmitoyltransferase 2, Very long-chain, medium-chain or long-chain 3-hydroxy AcylcoA Dehydrogenase Deficiencies) and 18 age, sex, and weight-matched normal healthy controls. Rd was similar between groups during the glycerol control clamp. Intramyocellular lipid (IMCL) content as measured by MRS increased after the 5 hour intralipid infusion in controls but not in participants with FAOD. Plasma free fatty acids during intralipid infusion were higher in FAOD compared to controls suggesting infused lipid remained in circulation. Muscle fiber type and expression of lipid transporters CD36 and FATP1 were similar in biopsy samples between groups and cannot explain decreased lipid uptake into muscle among FAOD subjects. However, intralipid suppressed Rd equally in subjects with FAOD and controls inducing peripheral insulin resistance in both groups. Impaired FAO decreased lipid accumulation in the muscle during intralipid infusion, but despite lower IMCL, subjects with FAOD developed peripheral insulin resistance similar to controls. Increased IMCL is not essential for, nor is reduced FAO flux protective against, the development of peripheral insulin resistance during intralipid infusion. Disclosure M.B.Gillingham: None. J.Q.Purnell: Advisory Panel; Boehringer Ingelheim International GmbH, Novo Nordisk. A.N.Gregor: None. O.Varlamov: None. J.J.Robino: None. C.E.Mccurdy: None. K.T.Greyslak: None. D.Choi: None. E.Baetscher: Consultant; Biogen. W.Rooney: Consultant; Ultragenix, Research Support; Revalesio. Funding National Institutes of Health (DK102813)

Activation of the Acute-Phase Response in Hemophilia.

To identify recurrent inflammation in hemophilia, we assessed the acute-phase response in the blood of patients with hemophilia A and B. Compared to age- and weight-matched controls, blood levels of interleukin-6 (IL-6), C-reactive protein (CRP), and LPS-binding protein (LBP) were significantly elevated in the entire cohort of hemophilia patients but exhibited a particularly pronounced increase in obese hemophilia patients with a body mass index (BMI) ≥30. Subgroup analysis of the remaining nonobese hemophilia patients (BMI: 18-29.9) revealed a significant spike of IL-6, CRP, and LBP in connection with a de-novo increase of soluble IL-6 receptor α (sIL-6Rα) in patients with bleeding events within the last month. Hemophilia patients who did not experience recent bleeding had IL-6, CRP, and sIL-6Rα blood levels similar to healthy controls. We did not find increased IL-6 or acute-phase reactants in hemophilia patients with arthropathy or infectious disease. The role of IL-6 as a marker of bleeding in hemophilia was confirmed in hemophilia patients with acute bleeding events as well as in transgenic hemophilia mice after needle puncture of the knee, which exhibited an extensive hematoma and a 150-fold increase of IL-6 blood levels within 7 days of the injury compared to needle-punctured control mice. Notably, IL-6 blood levels shrunk to a fourfold elevation in hemophilia mice over controls after 28 days, when the hematoma was replaced by arthrofibrosis. These findings indicate that acute-phase reactants in combination with sIL-6Rα could be sensitive biomarkers for the detection of acute and recent bleeding events in hemophilia.

Beat-to-beat resting blood pressure variability in patients with type 2 diabetes: effect of statin therapy

Type 2 diabetes (T2D) is a major health concern affecting more than 30 million people in the United States alone. Approximately two-thirds of patients with T2D develop hypertension, a major risk factor for cardiovascular disease. In addition to higher resting absolute blood pressure (BP), increased variability in BP has also been related to greater cardiovascular disease risk. However, whether patients with T2D display greater beat-to-beat BP variability remains unknown. Herein, we hypothesized that patients with T2D would exhibit greater beat-to-beat BP variability than age and body-weight-matched control subjects. In addition, since previous literature has shown that statins lower cardiovascular disease risk through favorable pleiotropic mechanisms, we further hypothesized that patients with T2D taking statins (T2D+statin) would have a lower beat-to-beat BP variability compared to patients with T2D not taking statins (T2D-statin). Beat-to-beat BP (finger photoplethysmography) and heart rate (ECG) were continuously measured, and absolute BP (automated sphygmomanometer) was measured periodically in patients with T2D (N=23; T2D+statin: N=10, T2D-statin: N=13) and age and body weight-matched control subjects (N=17). Measurements were made over the course of a quiet resting baseline period (9.5±1.3 minutes) with subjects in a supine position. Beat-to-beat BP variability was quantified as standard deviation (SD), range, and average real variability (average change in BP from one heartbeat to the next). Data are presented as mean ± standard deviation. Resting absolute systolic BP, diastolic BP, and mean arterial pressure (MAP) were not different between control subjects and T2D patients (P&gt;0.05 for all). There was also no difference in beat-to-beat systolic BP, diastolic BP, or MAP variability between the groups (e.g., MAP SD: control: 4.5±1.3 mmHg, T2D: 4.7±1.1 mmHg, P=0.763). When comparing T2D patients taking statins and those not taking statins, no difference was observed in absolute resting BP (P&gt;0.05). Likewise, systolic BP variability was not different between groups (SD: T2D-statin: 7.0±2.2 mmHg, T2D+statin: 6.3±1.4 mmHg, P=0.369). However, diastolic BP variability was significantly higher in T2D-statin patients (SD: T2D-statin: 4.1±1.1 mmHg, T2D+statin: 3.1±0.6 mmHg, P=0.013) and MAP variability tended to be higher (SD: T2D-statin: 5.2±1.4 mmHg, T2D+statin: 4.3±0.7 mmHg, P=0.061). Similar results were found for BP range and average real variability. These preliminary findings suggest that statin therapy may have a beneficial effect in lowering BP variability in patients with T2D. Supported by American Heart Association (AHA) - Institutional Award for Undergraduate Student Training - #915555. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Associations between eating in the absence of hunger and executive functions in adolescents with binge-eating disorder: An experimental study

Eating in the absence of hunger (EAH) is one of the key behavioral features of binge-eating disorder (BED) in youth. Although preliminary evidence revealed that adolescent BED co-occurs with deficits in executive functions (EFs), it is unclear whether EFs are related to EAH. Thus, this study experimentally examined whether deficits in EFs predict EAH in adolescents with and without BED. Adolescents (12–20 years) with BED (n = 28) and age-, sex-, and weight-matched controls (n = 28) underwent an EAH paradigm in the laboratory, where they were offered snacks ad libitum after having established satiety during a lunch meal. Cognitive interference, cognitive flexibility, decision making, and EFs in daily life were assessed by neuropsychological tests and self- and parent-report. The BED group showed a significantly higher food intake in gram during the EAH trial than controls with medium effect, but no significant group differences in EFs emerged. Dysfunctional decision making in terms of risky decision making, but no other EFs, predicted increased EAH (g, kcal) in the total sample. Although increases in risky decision making over adolescence are well known, this study uniquely revealed that general decision-making abilities driven by short-term reward may account for disinhibited eating behavior. Interventions targeting decision making with focus on reward sensitivity should be evaluated for their efficacy in preventing and reducing disinhibited eating behavior in adolescents.

Chronic consumption of a blend of inulin and arabinoxylan reduces energy intake in an ad libitum meal but does not influence perceptions of appetite and satiety: a randomised control-controlled crossover trial.

Prebiotic foods can be used to increase production of short-chain fatty acids (SCFA) in the gut. Of the SCFA, propionate is credited with the strongest anorectic activity. In previous work, a 50/50 blend of inulin and arabinoxylan was produced (I + AX) that significantly increased propionate production in an in vitro gut model. This study sought to establish whether chronic consumption of a prebiotic blend of I + AX decreases appetite and energy intake and increases intestinal propionate production in human participants. MIXSAT (clinicaltrials.gov id: NCT02846454, August 2016) was a double-blind randomised acute-within-chronic crossover feeding trial in healthy adult men (n = 20). Treatments were 8g per day I + AX for 21days or weight-matched maltodextrin control. The primary outcome measure was perceived satiety and appetite during an acute study visit. Secondary outcomes were energy intake in an ad libitum meal, faecal SCFA concentration, and faecal microbiota composition. Perceived satiety and appetite were not affected by the intervention. I + AX was associated with a reduction in energy intake in an ad libitum meal, increased faecal SCFA concentration, and an increase in cell counts of Bifidobacteria, Lactobacilli, and other microbial genera associated with health. Chronic consumption of this blend of prebiotics decreased energy intake in a single sitting. Further studies are needed to confirm mechanism of action and to determine whether this might be useful in weight control.

Impaired Physical Performance in X-linked Hypophosphatemia Is not Caused by Depleted Muscular Phosphate Stores.

X-linked hypophosphatemia (XLH) is a rare genetic disease, characterized by renal phosphate wasting and complex musculoskeletal manifestations including decreased physical performance. To characterize muscular deficits in patients with XLH and investigate phosphate stores in muscles. Case-control study (Muscle fatigability in X-linked Hypophosphatemia [MuXLiH]) with a 1-time assessment at the German Aerospace Center (DLR), Cologne, from May to December 2019, including patients with XLH cared for at the Osteology Department, University of Wuerzburg. Thirteen patients with XLH and 13 age/sex/body weight-matched controls aged 18-65 years were included. The main outcome measure was 31P-magnetic resonance spectroscopy (31P-MRS)-based assessment of phosphate metabolites in the soleus muscle at rest. Further analyses included magnetic resonance imaging-based muscle volume measurement, laboratory testing, isokinetic maximum voluntary contraction (MVC), fatigue testing, and jumping mechanography. By means of 31P-MRS, no significant differences were observed between XLH and controls regarding phosphate metabolites except for a slightly increased phosphocreatine to inorganic phosphate (PCr/Pi) ratio (XLH: 13.44 ± 3.22, control: 11.01 ± 2.62, P = .023). Quadriceps muscle volume was reduced in XLH (XLH: 812.1 ± 309.0 mL, control: 1391.1 ± 306.2 mv, P < .001). No significant differences were observed regarding isokinetic maximum torque (MVC) adjusted to quadriceps muscle volume. Jumping peak power and jump height were significantly reduced in XLH vs controls (both P < .001). The content of phosphoric compounds within the musculature of patients with XLH was not observed to be different from controls. Volume-adjusted muscle strength and fatiguability were not different either. Reduced physical performance in patients with XLH may result from long-term adaptation to reduced physical activity due to skeletal impairment.

Epigenetic Immune Cell Counting to Analyze Potential Biomarkers in Preterm Infants: A Proof of Principle in Necrotizing Enterocolitis.

Epigenetic immune cell counting is a DNA (de)methylation-based technique which can be used to quantify lymphocyte subsets on dried blood spots (DBS). The foregoing techniques allow for a retrospective investigation of immune cell profiles in newborns. In this study, we used this technique for determining lymphocyte subcounts as a potential biomarker for necrotizing enterocolitis (NEC). We investigated whether this technique can be implemented in the field of neonatology, by testing whether regulatory T cell (Treg) levels are pre-existently low in preterms with NEC. Newborn screening (NBS) cards from 32 preterms with NEC and 32 age- and weight-matched preterm controls, and 60 healthy term newborns, were analyzed. Relative and absolute cell counts were determined for CD3+, CD4+, CD8+, Th17, and Treg T cells. For both relative and absolute cell counts of CD3+, CD4+, CD8+, and Th17 T cells, significant differences were found between healthy term controls and both preterm groups, but not between preterm groups. For Tregs, no significant differences were found in either relative or absolute counts between any of the newborn groups. This study demonstrates the principle of epigenetic immune cell counting to analyze lymphocyte subsets in preterm neonates.

Increased insula and amygdala activity during selective attention for negatively valenced body parts in binge eating disorder.

Previous studies indicate that participants with eating disorders show an attentional bias for the negatively valenced body parts of their own body. However, the neural basis underlying these processes has not been investigated. We conducted a preregistered combined functional MRI (fMRI)/eye tracking study and presented 35 women with binge eating disorder (BED) and 24 weight-matched control subjects (CG) with body part images of their own body and a weight-matched unknown body. After the fMRI examination, participants rated the attractiveness of the presented body parts. As expected, women with BED responded with significantly higher insula and amygdala activity when viewing the negatively valenced body parts of their own body (compared to all other combinations). However, individuals with BED did not deviate from the CG in the processing of these stimuli in the ventromedial prefrontal cortex, the extrastriate body area or the fusiform body area. Our results indicate that the negative valued body parts carry a particularly strong emotional valence in individuals with BED. These results further emphasize the relevance of processing bias for negatively valenced body parts in the pathology of BED. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Dysregulation of Amino Acid, Lipid, and Acylpyruvate Metabolism in Idiopathic Intracranial Hypertension: A Non-targeted Case Control and Longitudinal Metabolomic Study.

Background: Idiopathic intracranial hypertension (IIH) is characterized by increased intracranial pressure occurring predominantly in women with obesity. The pathogenesis is not understood. We have applied untargeted metabolomic analysis using ultrahigh-performance liquid chromatography-mass spectrometry to characterize the cerebrospinal fluid (CSF) and serum in IIH compared to control subjects. Methods and findings: Samples were collected from IIH patients (n = 66) with active disease at baseline and again at 12 months following therapeutic weight loss. Control samples were collected from gender- and weight-matched healthy controls (n = 20). We identified annotated metabolites in CSF, formylpyruvate and maleylpyruvate/fumarylpyruvate, which were present at lower concentrations in IIH compared to control subjects and returned to values observed in controls following weight loss. These metabolites showed the opposite trend in serum at baseline. Multiple amino acid metabolic pathways and lipid classes were perturbed in serum and CSF in IIH alone. Serum lipid metabolite pathways were significantly increased in IIH. Conclusions: We observed a number of differential metabolic pathways related to amino acid, lipid, and acylpyruvate metabolism, in IIH compared to controls. These pathways were associated with clinical measures and normalized with disease remission. Perturbation of these metabolic pathways provides initial understanding of disease dysregulation in IIH.

134 The role of gut microbiota-derived metabolites in psoriasis

Gut microbiome alterations observed in patients with psoriasis might contribute to the disease pathogenesis through an increased intestinal permeability and translocation of several bacterial metabolites. The aim of the study was to assess the gut barrier dysfunction, concentration of intestinal microbiota-derived metabolites and their possible association with clinical manifestations and comorbidities of psoriasis. One hundred twenty patients with moderate to severe plaque psoriasis as well as 60 age- and weight-matched control were enrolled.