المؤلفون: Bannon, Christopher A, Meek, Claire L, Reimann, Frank, Gribble, Fiona M

مصطلحات موضوعية: BMI, GIP, GLP-1, Glucagon, Immunoassay, Insulin, Obesity, PYY, Humans, Male, Female, Adult, Fasting, Peptide YY, Middle Aged, Glucagon-Like Peptide 1, Gastric Inhibitory Polypeptide, Body Mass Index, Postprandial Period, Gastrointestinal Hormones

الوصف: Circulating insulin levels are known to be increased in people with higher body mass index (BMI) due to effects of adiposity on insulin resistance, whilst gut hormones have a more complex relationship, with fasting peptideYY (PYY) reported to be inversely related to BMI. This study aimed to further explore fasting and post prandial pancreatic and gut hormone concentrations in plasma samples from obese and non-obese participants. Participants with healthy BMI (n=15), overweight BMI (n=29) and obesity (n=161) had samples taken fasting and 30 min post mixed liquid meal for analysis of glucagon-like peptide-1 (GLP-1), PYY, glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon. Data visualiation used linear discriminant analysis for dimensionality reduction, to visualise the data and assess scaling of each hormone. Fasting levels of insulin, GIP and PYY were shown to be key classifiers between the 3 groups on ANCOVA analysis, with an observation of increased GIP levels in overweight, but not ...

الإتاحة: https://doi.org/10.17863/cam.106836Test
https://www.repository.cam.ac.uk/handle/1810/365603Test

المؤلفون: Rongfeng Qi, Zhihong Cao, Wesley Surento, Li Zhang, Lianli Qiu, Zhuoman Xia, Christopher R.K. Ching, Qiang Xu, Yan Yin, Long Jiang Zhang, Lingjiang Li, Yifeng Luo, Guang Ming Lu

المصدر: Journal of Affective Disorders. 314:318-324

مصطلحات موضوعية: Adult, Auditory Cortex, China, Polymorphism, Genetic, Genotype, Nuclear Receptor Subfamily 1, Group F, Member 1, Magnetic Resonance Imaging, Stress Disorders, Post-Traumatic, Psychiatry and Mental health, Clinical Psychology, Cross-Sectional Studies, Humans, Alleles, Genome-Wide Association Study

الوصف: The G allele in retinoid-related orphan receptor alpha (RORA, rs8042149) gene is associated with post-traumatic stress disorder (PTSD) diagnosis and more severe symptoms, reported in the first genome-wide association study of PTSD and subsequent replication studies. Although recent MRI studies identified brain structural deficits in RORA rs8042149 risk G allele carriers, the neural mechanism underlying RORA-related brain structural changes in PTSD remains poorly understood.This study included 227 Han Chinese adults who lost their only child. Cortical thickness and subcortical volume were extracted using FreeSurfer, and PTSD severity was assessed using the Clinician-Administered PTSD Scale. Hierarchical linear regression was used to assess the interaction effect between RORA genotypes (T/T, G/T, and G/G) and PTSD severity on cortical and subcortical structures.Significant genotype × PTSD symptom severity interaction effects were found for bilateral transverse temporal gyrus thickness. For individuals with the homozygous T/T genotype, current PTSD symptom severity was positively associated with bilateral transverse temporal gyrus thickness. For individuals with heterozygous G/T genotype, current PTSD symptom severity was negatively associated with the left transverse temporal gyrus thickness. No significant main or interaction effects were found in any subcortical regions.Cross-sectional design of this study.These findings suggest that the non-risk T/T genotype - but not the risk G allele carriers - has a potentially protective or compensatory role on temporal gyrus thickness in adults who lost their only child. These results highlight the moderation effect of RORA polymorphism on the relationship between PTSD symptom severity and cortical structural changes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2003a3eec71587eac909b16ec1913b29Test
https://doi.org/10.1016/j.jad.2022.07.044Test

المؤلفون: Boughton, Charlotte K, Hovorka, Roman

مصطلحات موضوعية: Artificial pancreas, Hybrid closed-loop, Inpatient diabetes, Psychosocial impact, Type 1 diabetes, Adult, Automation, Blood Glucose, Blood Glucose Self-Monitoring, Diabetes Mellitus, Type 1, Equipment Design, Female, Hospitalization, Humans, Hyperglycemia, Insulin, Insulin Infusion Systems, Male, Pancreas, Artificial, Pregnancy, Pregnancy in Diabetics

الوصف: Hybrid closed-loop (artificial pancreas) systems have recently been introduced into clinical practice for adults with type 1 diabetes. This reflects successful translation from research studies in highly supervised settings to evaluation of the technology in free-living home settings. We review the different closed-loop approaches and the key clinical evidence supporting adoption of hybrid closed-loop systems for adults with type 1 diabetes. We also discuss the growing evidence for automated insulin delivery in pregnant women and in hospitalized patients with hyperglycemia. We consider the psychosocial impact of closed-loop systems and the challenges and potential future advancements for automated insulin delivery.

وصف الملف: Print-Electronic; application/vnd.openxmlformats-officedocument.wordprocessingml.document

العلاقة: https://www.repository.cam.ac.uk/handle/1810/300531Test

الإتاحة: https://doi.org/10.17863/CAM.47605Test
https://www.repository.cam.ac.uk/handle/1810/300531Test

المؤلفون: Ibai Tamayo, Luis Forga, María José Goñi, Marta García-Mouriz, Natalia López-Andrés, Amaya Fernández-Celis

المصدر: Endocrinología, Diabetes y Nutrición. 69:322-330

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, genetic structures, Endocrinology, Diabetes and Metabolism, Logistic regression, Macular Edema, Nephropathy, Diabetic nephropathy, Endocrinology, Internal medicine, medicine, Humans, Diabetic Nephropathies, Type 1 diabetes, Diabetic Retinopathy, Nutrition and Dietetics, business.industry, Diabetic retinopathy, Odds ratio, Middle Aged, medicine.disease, Interleukin-1 Receptor-Like 1 Protein, Diabetes Mellitus, Type 1, Cohort, Female, business, Retinopathy

الوصف: Aim To determine the association and the prognostic value of soluble ST2 (sST2) levels in the development of diabetic retinopathy (DR), diabetic macular oedema (DMO) or diabetic nephropathy (DN), in a cohort of patients with type 1 diabetes (T1D). Methods A total of 269 individuals with T1D (154 males and 115 females) were recruited. The overall mean age was 43.2 ± 14.9 years, and the diabetes duration was 17.1 ± 12.1 years. Levels of sST2 in serum were evaluated, and the presence as well as the degree of DR, DMO and DN was recorded. Additionally, other clinical and analytical parameters including demographic variables were recovered from patients’ electronic health record. Ten years later, the presence and stage of DR, DMO and DN were again recorded under the same criteria. The association between previously mentioned parameters with DR and DN was analysed by univariate and multivariate logistic regression. The variables in the final multivariate models were adjusted from complete models via backward elimination and maintained only when significant. Results An increase of 10 ng/ml in the levels of sST2 was associated with a 1.50 (1.02–2.19) and 1.48 (1.05–2.08) prevalence odds ratio (OR) in DMO and DR, respectively. There was no association between sST2 levels and DN. Meanwhile, sST2 levels did not display a prognostic effect in any of the microangiopathic diabetic complications studied. Conclusions Levels of sST2 are associated with the presence of DR and DMO, they do not seem to be predictive for the development or deterioration of DR, DMO or DN.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::39145ca401098d175ad8714f42307885Test
https://doi.org/10.1016/j.endinu.2021.05.007Test

المؤلفون: Anne-Sophie Brazeau, Virginie Messier, Meryem K. Talbo, Claudia Gagnon, Nadine Taleb, Isabel Fortier, Zekai Wu, Bruce A. Perkins, André C. Carpentier, Aude Bandini, Rémi Rabasa-Lhoret

المصدر: Canadian Journal of Diabetes. 46:813-821

مصطلحات موضوعية: Adult, Male, Blood Glucose, Canada, Blood Glucose Self-Monitoring, Endocrinology, Diabetes and Metabolism, General Medicine, Middle Aged, Hypoglycemia, Diabetes Mellitus, Type 1, Cross-Sectional Studies, Insulin Infusion Systems, Endocrinology, Internal Medicine, Humans, Hypoglycemic Agents, Insulin, Female, Self Report, Registries, Patient Participation

الوصف: The BETTER (BEhaviors, Therapies, TEchnologies and hypoglycemic Risk in Type 1 diabetes) registry is a type 1 diabetes population surveillance system codeveloped with patient partners to address the burden of hypoglycemia and assess the impact of new therapies and technologies. The aim of this report was to describe the baseline characteristics of the BETTER registry cohort.A cross-sectional baseline evaluation was performed of a Canadian clinical cohort established after distribution of an online questionnaire. Participants were recruited through clinics, public foundations, advertising and social media. As of February 2021, 1,430 persons ≥14 years of age and living with type 1 diabetes or latent-autoimmune diabetes (LADA) were enrolled. The trial was registered on ClinicalTrials.gov (NCT03720197).Participants were (mean ± standard deviation) 41.2±15.7 years old with a diabetes duration of 22.0±14.7 years, 62.0% female, 92.1% Caucasian and 7.8% self-reporting as LADA, with 40.9% using a continuous subcutaneous insulin infusion (CSII) system and 78.0% using a continuous glucose monitoring (CGM) system. The most recent glycated hemoglobin ≤7% was reported by 29.7% of participants. At least 1 episode of hypoglycemia3.0 mmol/L (level 2-H) in the last month was reported by 78.4% of participants, with a median (interquartile range) of 5 (3, 10) episodes. The occurrence of severe hypoglycemia (level 3-H) in the last 12 months was reported by 13.3% of participants. Among these, the median number of episodes was 2 (1, 3).We have established the first surveillance registry for people living with type 1 diabetes in Canada relying on patient-reported outcomes and experiences. Hypoglycemia is a highly prevalent burden despite a relatively wide adoption of CSII and CGM use.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a97455d6b0e706aa812aa626d241cc77Test
https://doi.org/10.1016/j.jcjd.2022.05.010Test

المؤلفون: Yongwen Luo, Zhonghua Yang, Ying Yu, Peng Zhang

المصدر: International Journal of Biological Macromolecules. 222:2225-2243

مصطلحات موضوعية: Adult, Male, Neovascularization, Pathologic, Structural Biology, Cell Line, Tumor, Humans, Prostatic Neoplasms, General Medicine, Hypoxia-Inducible Factor 1, alpha Subunit, Hypoxia, Molecular Biology, Biochemistry

الوصف: Prostate cancer (PCa) is one of the most prevalent malignancies in adult males. However, PCa is resistant to multi-kinase inhibitors-based anti-angiogenic therapies, and the mechanism and effective targeting thereof remains unclear. In this study, single-cell and bulk-transcriptomic datasets analysis revealed that KIAA1199, a hyaluronic acid (HA) binding protein, was involved in glycolysis, hypoxia and angiogenesis pathways. Moreover, boosted KIAA1199 expression in PCa tissues was positively correlated with tumor stage, hypoxia-inducible factor (HIF)-1α overexpression, as well as angiogenesis markers. Tube formation, Western blot, enzyme-linked immunosorbent assay, and in vivo tumorigenesis results demonstrated that KIAA1199 silencing significantly inhibited angiogenesis and vasculogenic mimicry (VM), both in vitro and in vivo, by increasing semaphoring 3A (sema3A) expression while decreasing expressions of VEGFA, VE-cadherin, phosphorylated EphA2, and depolymerized HA levels. KIAA1199 overexpression was also found to promote angiogenesis and VM via increasing secretory VEGFA, however, this activity could be reversed by the HA biosynthesis inhibitor 4-methylumbelliferone (4MU). Furthermore, dual-luciferase and ChIP-PCR revealed that HIF1α is the transcriptional enhancer of KIAA1199, while lactate imported to PCa cells by monocarboxylate transporter 1 (MCT1) stabilizes HIF1α under normoxia via HIF1α lactylation. Our findings may provide a better understanding of angiogenesis and a promising therapeutic target of PCa.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::65a7c56d6b19c0b31ab48adc0b930e02Test
https://doi.org/10.1016/j.ijbiomac.2022.10.014Test

المؤلفون: Faye L. Norby, Kyndaron Reinier, Audrey Uy-Evanado, Gregory A. Nichols, Eric C. Stecker, Jonathan Jui, Sumeet S. Chugh

المصدر: Mayo Clinic Proceedings. 97:2271-2281

مصطلحات موضوعية: Adult, Aged, 80 and over, Male, Adolescent, General Medicine, Middle Aged, Heart Arrest, Diabetes Mellitus, Type 1, Death, Sudden, Cardiac, Diabetes Mellitus, Type 2, Risk Factors, Humans, Female, Prospective Studies, Aged

الوصف: To investigate the association between type 1 diabetes mellitus (T1D) and type 2 diabetes mellitus (T2D) with risk of sudden cardiac arrest (SCA).In a prospective community-based study of SCA from February 1, 2002, through November 30, 2019, we ascertained 2771 cases age 18 years of age or older and matched them to 8313 controls based on geography, age, sex, and race/ethnicity. We used logistic regression to evaluate the independent association between diabetes, T1D, T2D, and SCA.Patients had a mean age of 64.5±15.9 years, were 33.3% female and 23.9% non-White race. Overall, 36.7% (n=1016) of cases and 23.8% (n=1981) of controls had diabetes. Among individuals with diabetes, the proportion of T1D was 6.5% (n=66) among cases and 2.0% among controls (n=40). Diabetes was associated with 1.5-times higher odds of SCA. Compared with those without diabetes, the odds ratio and 95% CI for SCA was 4.36 (95% CI, 2.81 to 6.75; P.001) in T1D and 1.45 (95% CI, 1.30 to 1.63; P.001) in T2D after multivariable adjustment. Among those with diabetes, the odds of having SCA were 2.41 times higher in T1D than in T2D (95% CI, 1.53 to 3.80; P.001). Cases of SCA with T1D were more likely to have an unwitnessed arrest, less likely to receive resuscitation, and less likely to survive compared with those with T2D.Type 1 diabetes was more strongly associated with SCA compared with T2D and had less favorable outcomes following resuscitation. Diabetes type could influence the approach to risk stratification and prevention of SCA.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::27c8acb49964433f9c01878e6d074a2eTest
https://doi.org/10.1016/j.mayocp.2022.05.021Test

المؤلفون: Shweta, Urva, Tamer, Coskun, Mei Teng, Loh, Yu, Du, Melissa K, Thomas, Sirel, Gurbuz, Axel, Haupt, Charles T, Benson, Martha, Hernandez-Illas, David A, D'Alessio, Zvonko, Milicevic

المصدر: The Lancet. 400:1869-1881

مصطلحات موضوعية: Adult, Body Weight, Gastric Inhibitory Polypeptide, General Medicine, Middle Aged, Glucagon, Glucagon-Like Peptide-1 Receptor, Young Adult, Glucose, Diabetes Mellitus, Type 2, Double-Blind Method, Glucagon-Like Peptide 1, Receptors, Glucagon, Humans, Obesity, Aged

الوصف: Treating hyperglycaemia and obesity in individuals with type 2 diabetes using multi-receptor agonists can improve short-term and long-term outcomes. LY3437943 is a single peptide with agonist activity for glucagon, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1) receptors that is currently in development for the treatment of type 2 diabetes and for the treatment of obesity and associated comorbidities. We investigated the safety, pharmacokinetics, and pharmacodynamics of multiple weekly doses of LY3437943 in people with type 2 diabetes in a 12-week study.In this phase 1b, proof-of-concept, double-blind, placebo-controlled, randomised, multiple-ascending dose trial, adults (aged 20-70 years) with type 2 diabetes for at least 3 months, a glycated haemoglobin ABetween Dec 18, 2019, and Dec 28, 2020, 210 people were screened, of whom 72 were enrolled, received at least one dose of study drug, and were included in safety analyses. 15 participants had placebo, five had dulaglutide 1·5 mg and, for LY3437943, nine had 0·5 mg, nine had 1·5 mg, 11 had 3 mg, 11 had 3/6 mg, and 12 had 3/6/9/12 mg. 29 participants discontinued the study prematurely. Treatment-emergent adverse events were reported by 33 (63%), three (60%), and eight (54%) participants who received LY3437943, dulaglutide 1·5 mg, and placebo, respectively, with gastrointestinal disorders being the most frequently reported treatment-emergent adverse events. The pharmacokinetics of LY3437943 were dose proportional and its half-life was approximately 6 days. At week 12, placebo-adjusted mean daily plasma glucose significantly decreased from baseline at the three highest dose LY3437943 groups (least-squares mean difference -2·8 mmol/L [90% CI -4·63 to -0·94] for 3 mg; -3·1 mmol/L [-4·91 to -1·22] for 3/6 mg; and -2·9 mmol/L [-4·70 to -1·01] for 3/6/9/12 mg). Placebo-adjusted sHbAIn this early phase study, LY3437943 showed an acceptable safety profile, and its pharmacokinetics suggest suitability for once-weekly dosing. This finding, together with the pharmacodynamic findings of robust reductions in glucose and bodyweight, provides support for phase 2 development.Eli Lilly and Company.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1c6fbf9575e306306e92cc4c2bbb96b7Test
https://doi.org/10.1016/s0140-6736Test(22)02033-5

المؤلفون: Mark A. Clements, Alexandra D. Monzon, Arwen M. Marker, Susana R. Patton

المصدر: Can J Diabetes

مصطلحات موضوعية: Adult, Parents, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, Telehealth, Article, Endocrinology, Diabetes mellitus, Intervention (counseling), Internal Medicine, medicine, Humans, Child, Video based, Glycated Hemoglobin, Type 1 diabetes, business.industry, General Medicine, Middle Aged, medicine.disease, Hypoglycemia, Telemedicine, Distress, Diabetes Mellitus, Type 1, Physical therapy, business

الوصف: Our aim in this study was to refine and pilot a video-based telehealth intervention to reduce diabetes distress, depressive symptoms and hypoglycemia fear in parents of school-age children with type 1 diabetes and to assess for changes in child glycated hemoglobin (A1C).We recruited 41 parents of children (5 to 12 years) to participate in a manualized, video-based telehealth intervention (Cognitive Adaptions to Reduce Emotional Stress [CARES]). Of these, 29 parents completed either a 12-week (n=13) or 8-week (n=16) version of CARES based on the timing of their recruitment. We assessed feasibility (i.e. attrition, attendance) and parent satisfaction with CARES. We used repeated-measures analysis of variance with parent group (8 vs 12 sessions) as a between-subject variable and time as a within-subject variable to measure change in our dependent variables.Mostly mothers participated (97.3%). Parents' mean age was 39.65±6.84 years and children's mean age was 9.86±1.57 years at pretreatment. CARES had low attrition (20% to 25%) and good attendance (96% to 98%). Parents also reported high levels of treatment satisfaction (85%). There were significant main effects for time for parent-reported diabetes distress and depressive symptoms at posttreatment and 3-month follow-up. There was a statistical trend suggesting a time × group interaction for parent depressive symptoms at posttreatment. There was a significant main effect for time for hypoglycemia fear at the 3-month follow-up but no change at posttreatment. There was no change in child A1C at posttreatment.CARES showed high parent satisfaction, good feasibility and promising results for reducing diabetes distress in parents of school-age children with type 1 diabetes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d28e64ca0b105429e428e5d0935993a5Test
https://doi.org/10.1016/j.jcjd.2021.10.007Test

المؤلفون: Sethuraman, Visalakshi, Pu, Yong, Gingrich, Jeremy, Jing, Jiongjie, Long, Robert, Olomu, Isoken Nicholas, Veiga-Lopez, Almudena

المصدر: Pregnancy Hypertens

مصطلحات موضوعية: Adult, Male, Placenta, Infant, Newborn, Gene Expression Regulation, Developmental, Obstetrics and Gynecology, Article, Cholesterol, Pre-Eclampsia, Pregnancy, Case-Control Studies, Internal Medicine, Humans, Female, RNA, Messenger, ATP Binding Cassette Transporter 1, ATP Binding Cassette Transporter, Subfamily G, Member 1

الوصف: Preeclampsia complicates 2-8% of pregnancies and is associated with prematurity and intrauterine growth restriction. Cholesterol and sterol transport is a key function of the placenta and it is elicited through ATP binding cassette (ABC) transporters. ABCA1 expression changes during trophoblast cell fusion, a process required to form the placental syncytium that enables maternal-fetal nutrient transfer. ABCA1 expression is dysregulated in preeclamptic placentas. But whether ABC transporters expression during trophoblast fusion is disrupted in preeclampsia remains unknown. We investigated if cholesterol and sterol ABC transporters are altered in term and preterm preeclampsia placentas and during human cytotrophoblast syncytialization. Human placental biopsies were collected from healthy term (≥37 weeks; n = 11) and term preeclamptic (≥36 6/7 weeks; n = 8) and pre-term preeclamptic (28-35 weeks; n = 8) pregnancies. Both, protein and mRNA expression for ABCA1, ABCG1, ABCG5, and ABCG8 were evaluated. Primary cytotrophoblasts isolated from a subset of placentas were induced to syncytialize for 96 h and ABCA1, ABCG1 and ABCG8 mRNA expression evaluated at 0 h and 96 h. Protein and gene expression of ABC transporters were not altered in preeclamptic placentas. In the healthy Term group, ABCA1 expression was similar before and after syncytialization. After 96 h of syncytialization, mRNA expression of ABCA1 and ABCG1 increased significantly, while ABCG8 decreased significantly in term-preeclampsia, but not pre-term preeclampsia. While placental expression of ABCA1 and ABCG1 remained unaltered in term preeclampsia, the disruption in their dynamic expression pattern during cytotrophoblast syncytialization suggests that cholesterol transport may contribute to the pathophysiologic role of the placenta in preeclampsia.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::38ed322bcde6cd48bd79e25888f68fd2Test
https://doi.org/10.1016/j.preghy.2022.01.006Test