المؤلفون: Rose Gubitosi-Klug, Ionut Bebu, Victoria R. Trapani, Naomi Chaytor, John M. Lachin, José A. Luchsinger, Susan M. Hitt, Kaleigh Farrell, Gayle M. Lorenzi, Christopher M. Ryan, Alan M. Jacobson, Barbara H. Braffett

المصدر: The Lancet Diabetes & Endocrinology. 9:436-445

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Pediatrics, Time Factors, Adolescent, Endocrinology, Diabetes and Metabolism, Psychological intervention, 030209 endocrinology & metabolism, Young Adult, 03 medical and health sciences, Cognition, 0302 clinical medicine, Endocrinology, Diabetes mellitus, Epidemiology, Internal Medicine, medicine, Humans, Cognitive Dysfunction, 030212 general & internal medicine, Effects of sleep deprivation on cognitive performance, Cognitive decline, Aged, Psychomotor learning, Type 1 diabetes, business.industry, Middle Aged, medicine.disease, Diabetes Mellitus, Type 1, Female, business, Follow-Up Studies, Kidney disease

الوصف: Summary Background With improved treatment, individuals with type 1 diabetes are living longer but there is limited information on the effects of type 1 diabetes on cognitive ability as they become older adults. We followed up individuals with type 1 diabetes to identify independent risk factors for cognitive decline as people age. Methods 1051 participants with type 1 diabetes enrolled in the Diabetes Control and Complications Trial (DCCT) and its follow-up Epidemiology of Diabetes Interventions and Complications (EDIC) study. Participants completed cognitive assessments at baseline (median age 27 years) and 2, 5, 18, and 32 years later (median age 59). HbA1c levels, frequency of severe hypoglycaemia, non-glycemic risk factors such as elevated blood pressure, and microvascular and macrovascular complications were assessed repeatedly. We examined the effects of these on measures of memory and psychomotor and mental efficiency. These studies are registered with clinicaltrials.gov , NCT00360815 (DCCT) and NCT00360893 (EDIC). Findings Over 32 years of follow-up, we found substantive declines in memory and psychomotor and mental efficiency. Between 18 and 32 years of follow-up, the decline in psychomotor and mental efficiency was five times larger than the change from baseline to year 18. Independent of the other risk factors and comorbidities, exposure to higher HbA1c levels, more episodes of severe hypoglycaemia, and elevated systolic blood pressure were associated with greater decrements in psychomotor and mental efficiency that was most notable by year 32 (p Interpretation Cognitive function declines with ageing in type 1 diabetes. The association of glycaemia and blood pressure levels with cognitive decline suggests that better management might preserve cognitive function. Funding United States National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Disease.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eea121943079d34017f2fed67a2076f5Test
https://doi.org/10.1016/s2213-8587Test(21)00086-3

المؤلفون: Samim Özen, Yasemin Atik Altınok, Şükran Darcan, Damla Gökşen, Günay Demir

المصدر: Journal of Clinical Research in Pediatric Endocrinology
JCRPE, Vol 13, Iss 2, Pp 198-203 (2021)

مصطلحات موضوعية: Male, Time Factors, Endocrinology, Diabetes and Metabolism, Physiology, Dawn phenomenon, Pediatrics, 0302 clinical medicine, Endocrinology, Bolus (medicine), American-Diabetes-Association, Insulin, 030212 general & internal medicine, insulin infusion pump therapy, Child, Morning, basal rates, Infusion Pumps, Implantable, Growth hormone secretion, Circadian Rhythm, Subcutaneous Insulin Infusion, Type 1 diabetes, Child, Preschool, Original Article, Female, Insulin pump, Adult, Basal rate, Adolescent, 030209 endocrinology & metabolism, RJ1-570, Diseases of the endocrine glands. Clinical endocrinology, European-Association, 03 medical and health sciences, Young Adult, Age, Insulin Infusion Systems, medicine, Humans, Hypoglycemic Agents, Circadian rhythm, basal insulin, business.industry, Mellitus, Consensus Statement, Infant, RC648-665, medicine.disease, Diabetes Mellitus, Type 1, Pediatrics, Perinatology and Child Health, Therapy, Insulin Resistance, Young-Adults, business, Appraisal

الوصف: Objective: Pump-treated children with type 1 diabetes (T1DM) have widely differing basal insulin (BI) infusion profiles for specific periods of the day. The pattern of BI requirements depends on the timing and magnitude of cortisol and growth hormone secretion within each age group. In adolescents and young adults, a decreased insulin sensitivity is seen, particularly in the early morning (dawn phenomenon) and to a lesser extent, in the late afternoon (dusk phenomenon). Different approaches exist for the inititation of basal rates. However, there is a lack of evidence-based recommendation, especially in young children. Usually the basal rates are set equally throughout day and night or the day is divided into tertiles. The aim of this study was to analyze the change of the initial, equally distributed, BI rates over the first year of standard insulin pump therapy. Methods: A total of 154 patients with T1DM, aged between 0 and 18 years, (n=5). Distribution of hourly basal rates at the initiation of the pump and at the end of first year were evaluated. Results: Median (range) age and diabetes duration was 14.46 (1.91-26.15) and 7.89 (1.16-17.15) years, respectively. Forty-four percent were male, 56% were female. Mean total insulin dose/kg in the whole cohort at the initiation and after one year of pump therapy was 0.86 +/- 0.23 U/kg and 0.78 +/- 0.19 U/kg, respectively and differed significantly between each age group (p

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::042811ee54a19ba17a3880a5ce10811bTest
http://europepmc.org/articles/PMC8186333Test

المؤلفون: Anthony C Keech, Yoon Hi Cho, Ryan J. Farr, Emma S. Scott, David N O'Neal, Anandwardhan A. Hardikar, Paul Z. Benitez-Aguirre, Mugdha V. Joglekar, Andrzej S. Januszewski, Luke M. Carroll, Alicia J. Jenkins, Maria E. Craig, Yik Wen Loh, Wilson K. M. Wong, Kim C. Donaghue

المصدر: Scientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
Scientific Reports

مصطلحات موضوعية: Blood Glucose, Male, 0301 basic medicine, Diabetes duration, medicine.medical_treatment, Autoimmunity, 0302 clinical medicine, Insulin-Secreting Cells, Insulin Secretion, Medicine, Child, Aged, 80 and over, Multidisciplinary, C-Peptide, Age Factors, Middle Aged, Type 1 diabetes, Female, Adult, medicine.medical_specialty, Adolescent, Science, 030209 endocrinology & metabolism, Article, Young Adult, 03 medical and health sciences, Diabetes mellitus, Internal medicine, microRNA, Humans, Secretion, Circulating MicroRNA, Insulin secretion, Aged, Autoantibodies, Glycated Hemoglobin, business.industry, Insulin, medicine.disease, MicroRNAs, Diabetes Mellitus, Type 1, 030104 developmental biology, Endocrinology, Gene Expression Regulation, Genetic markers, Age of onset, business, Biomarkers

الوصف: The aim of this cross-sectional study was to compare plasma C-peptide presence and levels in people without diabetes (CON) and with Type 1 diabetes and relate C-peptide status to clinical factors. In a subset we evaluated 50 microRNAs (miRs) previously implicated in beta-cell death and associations with clinical status and C-peptide levels. Diabetes age of onset was stratified as adult (≥ 18 y.o) or childhood ( 20 years. Plasma C-peptide was measured by ultrasensitive ELISA. Plasma miRs were quantified using TaqMan probe-primer mix on an OpenArray platform. C-peptide was detectable in 55.3% of (n = 349) people with diabetes, including 64.1% of adults and 34.0% of youth with diabetes, p p p = 0.02, respectively]. In the childhood-onset group more people with longer diabetes duration (> 20 years) had detectable C-peptide (60%) than in those with shorter diabetes duration (39%, p for trend

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cbd5b712c5082c4c879f559920494d80Test
https://doaj.org/article/b1ec56fdb12a4c0cb5cb32be78d2f006Test

المؤلفون: Martin Haupt-Jorgensen, Karsten Buschard, Flemming Pociot, Kristina Pedersen, Knut Dahl-Jørgensen, Ivan C. Gerling, Simranjeet Kaur, Lars Krogvold

المصدر: Diabetologia
Pedersen, K, Haupt-Jorgensen, M, Krogvold, L, Kaur, S, Gerling, I C, Pociot, F, Dahl-Jørgensen, K & Buschard, K 2021, ' Genetic predisposition in the 2′-5′A pathway in the development of type 1 diabetes : potential contribution to dysregulation of innate antiviral immunity ', Diabetologia, vol. 64, no. 8, pp. 1805-1815 . https://doi.org/10.1007/s00125-021-05469-5Test

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Ribonuclease L, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, Disease, Type 2 diabetes, Biology, Interferon α, RNase L, Type 1 interferon, Antiviral Agents, Polymorphism, Single Nucleotide, Article, Virus, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Immune system, Internal Medicine, Genetic predisposition, medicine, Humans, Genetic Predisposition to Disease, RNA, Messenger, Gene, Type 1 diabetes, Oligoribonucleotides, Adenine Nucleotides, RNA-Binding Proteins, medicine.disease, Immunity, Innate, Toll-like receptor 7, Diabetes Mellitus, Type 1, 030104 developmental biology, Gene Expression Regulation, Virus Diseases, Immunology, 2′-5′A pathway, 2′-5′ Oligoadenylate synthetase, Female, Genome-Wide Association Study

الوصف: Aims/hypothesis The incidence of type 1 diabetes is increasing more rapidly than can be explained by genetic drift. Viruses may play an important role in the disease, as they seem to activate the 2′-5′-linked oligoadenylate (2′-5′A) pathway of the innate antiviral immune system. Our aim was to investigate this possibility. Methods Innate antiviral immune pathways were searched for type 1 diabetes-associated polymorphisms using genome-wide association study data. SNPs within ±250kb flanking regions of the transcription start site of 64 genes were examined. These pathways were also investigated for type 1 diabetes-associated RNA expression profiles using laser-dissected islets from two to five tissue sections per donor from the Diabetes Virus Detection (DiViD) study and the network of Pancreatic Organ Donors (nPOD). Results We found 27 novel SNPs in genes nominally associated with type 1 diabetes. Three of those SNPs were located upstream of the 2′-5′A pathway, namely SNP rs4767000 (p = 1.03 × 10−9, OR 1.123), rs1034687 (p = 2.16 × 10−7, OR 0.869) and rs739744 (p = 1.03 × 10−9, OR 1.123). We also identified a large group of dysregulated islet genes in relation to type 1 diabetes, of which two were novel. The most aberrant genes were a group of IFN-stimulated genes. Of those, the following distinct pathways were targeted by the dysregulation (compared with the non-diabetic control group): OAS1 increased by 111% (p < 1.00 × 10−4, 95% CI −0.43, −0.15); MX1 increased by 142% (p < 1.00 × 10−4, 95% CI −0.52, −0.22); and ISG15 increased by 197% (p = 2.00 × 10−4, 95% CI −0.68, −0.18). Conclusions/interpretation We identified a genetic predisposition in the 2′-5′A pathway that potentially contributes to dysregulation of the innate antiviral immune system in type 1 diabetes. This study describes a potential role for the 2′-5′A pathway and other components of the innate antiviral immune system in beta cell autoimmunity. Graphical abstract

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bc7c11e2de9bab5e6655271157f4e1c3Test
https://doi.org/10.1007/s00125-021-05469-5Test

المؤلفون: Sarah H. Wild, Karen Madill, Shareen Forbes, Laura Reid, Fraser W. Gibb, Helen M. Colhoun, Baljean Dhillon, Mark W J Strachan

المصدر: Reid, L, Gibb, F W, Colhoun, H M, Wild, S H, Strachan, M W J, Madill, K, Dhillon, B & Forbes, S 2021, ' Continuous subcutaneous insulin infusion therapy is associated with reduced retinopathy progression compared with multiple daily injections of insulin ', Diabetologia . https://doi.org/10.1007/s00125-021-05456-wTest
Diabetologia

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Microvascular complications, Adolescent, Injections, Subcutaneous, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Blood Pressure, 030209 endocrinology & metabolism, Infusions, Subcutaneous, Article, Young Adult, 03 medical and health sciences, Insulin Infusion Systems, Clinical science, 0302 clinical medicine, Infusion therapy, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Insulin, 030212 general & internal medicine, Child, Retinopathy, Proportional Hazards Models, Retrospective Studies, Glycated Hemoglobin, Type 1 diabetes, Diabetic Retinopathy, business.industry, Retrospective cohort study, Diabetic retinopathy, medicine.disease, Cholesterol, Diabetes Mellitus, Type 1, Blood pressure, Disease Progression, Insulin therapy, Female, business, Clinical diabetes

الوصف: Aims/hypothesis We aimed to compare diabetic retinopathy outcomes in people with type 1 diabetes following introduction of continuous subcutaneous insulin infusion (CSII) therapy with outcomes in people receiving continuing therapy with multiple daily insulin injections (MDI). Methods This is a retrospective cohort study using the Scottish Care Information – Diabetes database for retinal screening outcomes and HbA1c changes in 204 adults commenced on CSII therapy between 2013 and 2016, and 211 adults eligible for CSII during the same period but who continued on MDI therapy. Diabetic retinopathy progression (time to minimum one-grade worsening in diabetic retinopathy from baseline grading) was plotted for CSII and MDI cohorts using Kaplan–Meier curves, and outcomes were compared using multivariate Cox regression analysis adjusting for age, sex, baseline HbA1c, blood pressure, cholesterol, smoking status and socioeconomic quintile. Impact of baseline HbA1c and change in HbA1c on diabetic retinopathy progression was assessed within CSII and MDI cohorts. Results CSII participants were significantly younger, were from less socially deprived areas, and had lower HbA1c and higher diastolic BP at baseline. There was a larger reduction in HbA1c at 1 year in those on CSII vs MDI (−6 mmol/mol [−0.6%] vs −2 mmol/mol [−0.2%], p p = 0.0097). High baseline HbA1c (75 mmol/mol [9%]) was associated with diabetic retinopathy progression in the MDI group (p = 0.0049) but not the CSII group (p = 0.93). Change in HbA1c at follow-up, irrespective of baseline glycaemic status, did not significantly affect diabetic retinopathy progression in either group. Conclusions/interpretation CSII was associated with reduced diabetic retinopathy progression compared with continued MDI therapy, and may be protective against diabetic retinopathy progression for those with high baseline HbA1c. Progression of diabetic retinopathy over 3 years was not associated with a change in HbA1c. Graphical abstract

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::878811d6c8ce2bb76eecb3308bccd634Test
https://doi.org/10.1007/s00125-021-05456-wTest

المؤلفون: Ayman A. Al Hayek, Mohamed Abdulaziz Al Dawish, Asirvatham Alwin Robert

المصدر: Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 15:747-751

مصطلحات موضوعية: Adult, Blood Glucose, Male, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Saudi Arabia, Insulin delivery, 030209 endocrinology & metabolism, Glycemic Control, Hypoglycemic episodes, Young Adult, 03 medical and health sciences, Insulin Infusion Systems, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Internal Medicine, Humans, Hypoglycemic Agents, Insulin, Medicine, Prospective Studies, 030212 general & internal medicine, Prospective cohort study, Glycemic, Type 1 diabetes, business.industry, General Medicine, Prognosis, medicine.disease, Hypoglycemia, Diabetes Mellitus, Type 1, Postprandial, Patient Satisfaction, Female, business, Biomarkers, Follow-Up Studies

الوصف: Background and aims To determine the efficacy of i-Port Advance system on patients satisfaction and glycemic control among patients with type 1 diabetes (T1D). Methods This prospective study was performed among 73 patients with T1D (13–29 years) at Prince Sultan Military Medical City, Riyadh, Saudi Arabia. Demographic data were collected at baseline and clinical characteristics were collected at baseline and 12 weeks. Patients’ responses to Morisky Medication Adherence Scale (MMAS-8) and Insulin Delivery Satisfaction Survey (IDSS) were recorded at baseline and 12 weeks after initiating the i-Port Advance system. Results At 12 weeks, significant improvement was evident in the IDSS subscales, which comprises the IDSS effective (p = 0.048), burdensome (p = 0.032), and IDSS inconvenient (p = 0.001), with the total baseline IDSS score being 2.6 ± 0.42, and at 12 weeks being 3.7 ± 0.72 (p = 0.037). The MMAS total score at baseline was 4.6 ± 1.2, and at 12 weeks, it increased to 6.4 (p = 0.028). HbA1c level was 8.4% at baseline and decreased to 7.9% (p = 0.001) at 12 weeks. The total daily dose of insulin at baseline registered 0.9 ± 0.13, which declined to 0.8 ± 0.12 (p = 0.048) at 12 weeks. Fasting blood sugar value was 197 ± 23.4 at baseline, which dropped to 182 ± 24.5 at 12 weeks (p = 0.01); and the postprandial glucose at baseline was 195 ± 21.4 and declined to 177 ± 19.2 at 12 weeks (p = 0.01). The hypoglycemic episodes revealed a noteworthy reduction after the i-Port Advance system usage. Conclusion Use of i-Port Advance system was found to raise the patients’ satisfaction levels and lower both the hypoglycemic episodes as well as the HbA1c levels.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::6747559d045720ca60ae9f0e324eaba1Test
https://doi.org/10.1016/j.dsx.2021.03.028Test

المؤلفون: Niels Jessen, Bjørn Richelsen, Steen B. Pedersen, Peter Breining, Jacob B. Hansen, Mads Kjolby

المصدر: Breining, P, Pedersen, S B, Kjolby, M, Hansen, J B, Jessen, N & Richelsen, B 2021, ' Parathyroid hormone receptor stimulation induces human adipocyte lipolysis and browning ', European Journal of Endocrinology, vol. 184, no. 5, pp. 687-697 . https://doi.org/10.1530/EJE-20-0713Test

مصطلحات موضوعية: Adult, Male, endocrine system, medicine.medical_specialty, Adipose Tissue, Brown/metabolism, Lipolysis, Endocrinology, Diabetes and Metabolism, Receptor expression, Parathyroid hormone, Adipose tissue, Parathyroid Hormone/pharmacology, 030209 endocrinology & metabolism, White adipose tissue, Lipolysis/drug effects, Adipose Tissue/drug effects, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Adipose Tissue, Brown, Receptor, Parathyroid Hormone, Type 1/metabolism, Adipocyte, Internal medicine, Brown adipose tissue, Adipocytes, medicine, Humans, Uncoupling Protein 1, Receptor, Parathyroid Hormone, Type 1, Aged, Chemistry, Thermogenesis/drug effects, Thermogenesis, Uncoupling Protein 1/metabolism, General Medicine, Middle Aged, Thermogenin, Cross-Sectional Studies, medicine.anatomical_structure, Adipose Tissue, Parathyroid Hormone, 030220 oncology & carcinogenesis, Female, hormones, hormone substitutes, and hormone antagonists, Adipocytes/drug effects

الوصف: Objective Activation of brown adipose tissue is a promising strategy to treat and prevent obesity and obesity-related disorders. Activation of uncoupling protein 1 (UCP1) leads to uncoupled respiration and dissipation of stored energy as heat. Induction of UCP1-rich adipocytes in white adipose tissue, a process known as ‘browning’, serves as an alternative strategy to increase whole body uncoupling capacity. Here, we aim to assess the association between parathyroid hormone (PTH) receptor expression and UCP1 expression in human adipose tissues and to study PTH effects on human white and brown adipocyte lipolysis and UCP1 expression. Design A descriptive study of human neck adipose tissue biopsies substantiated by an interventional study on human neck-derived adipose tissue cell models. Methods Thermogenic markers and PTH receptor gene expression are assessed in human neck adipose tissue biopsies and are related to individual health records. PTH-initiated lipolysis and thermogenic gene induction are assessed in cultured human white and brown adipocyte cell models. PTH receptor involvement is investigated by PTH receptor silencing. Results PTH receptor gene expression correlates with UCP1 gene expression in the deep-neck adipose tissue in humans. In cell models, PTH receptor stimulation increases lipolysis and stimulates gene transcription of multiple thermogenic markers. Silencing of the PTH receptor attenuates the effects of PTH indicating a direct PTH effect via this receptor. Conclusion PTH 1 receptor stimulation by PTH may play a role in human adipose tissue metabolism by affecting lipolysis and thermogenic capacity.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b9393d6212f2abdcb21a7db48ea58f29Test
https://doi.org/10.1530/eje-20-0713Test

المؤلفون: Barbara C. Galland, Esko Wiltshire, Jenny Rayns, James Stanley, Shelley Rose, Martin de Bock, Karen E MacKenzie, Sara E Boucher, Claire Smith, Benjamin J Wheeler

المصدر: Pediatric Diabetes. 22:823-831

مصطلحات موضوعية: Adult, Blood Glucose, Male, Pediatrics, medicine.medical_specialty, Adolescent, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Glycemic Control, Pittsburgh Sleep Quality Index, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Sleep debt, Risk Factors, Diabetes management, Diabetes mellitus, Internal Medicine, Humans, Medicine, 030212 general & internal medicine, Glycemic, Glycated Hemoglobin, Type 1 diabetes, business.industry, Actigraphy, medicine.disease, Sleep in non-human animals, Diabetes Mellitus, Type 1, Sleep Quality, Case-Control Studies, Pediatrics, Perinatology and Child Health, Female, Sleep, business, New Zealand

الوصف: BACKGROUND In type 1 diabetes mellitus (T1D), glycemic control and sleep have a bidirectional relationship, with unhealthy glycemic control impacting sleep, and inadequate sleep impacting diabetes management. Youth are at risk for poor quality sleep; however, little is known about sleep among youth with high-risk glycemic control. OBJECTIVE To assess differences in habitual sleep timing, duration, and quality among youth with T1D and controls. SUBJECTS Two-hundred-thirty youth (13-20 years): 64 with T1D (mean age 16.6 ± 2.1 years, 48% female, diabetes duration 7.5 ± 3.8 years, HbA1c 96 ± 18.0 mmol/mol [10.9 ± 1.7%]), and 166 controls (mean age 15.3 ± 1.5, 58% female). METHODS Comparison of data from two concurrent studies (from the same community) using subjective and objective methods to assess sleep in youth: Pittsburgh Sleep Quality Index evaluating sleep timing and quality; 7-day actigraphy measuring habitual sleep patterns. Regression analyses were used to compare groups. RESULTS When adjusted for various confounding factors, youth with T1D reported later bedtimes (+36 min; p

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7a36ad3802ba9ccf652e929bab8b82acTest
https://doi.org/10.1111/pedi.13215Test

المؤلفون: Agata Grzelka-Woźniak, Aleksandra Uruska, Paweł Niedźwiecki, Aleksandra Cieluch, Justyna Flotyńska, Ewa Wysocka, Dorota Zozulińska-Ziółkiewicz, Marcin Nowicki

المصدر: Nutrition, Metabolism and Cardiovascular Diseases. 31:1219-1226

مصطلحات موضوعية: Adult, Blood Glucose, Male, medicine.medical_specialty, Time Factors, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Medicine (miscellaneous), Pilot Projects, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, Phospholipid transfer protein, Internal medicine, Diabetes mellitus, Cholesterylester transfer protein, Humans, Hypoglycemic Agents, Insulin, Medicine, Prospective Studies, Phospholipid Transfer Proteins, Type 1 diabetes, Nutrition and Dietetics, biology, business.industry, Reverse cholesterol transport, medicine.disease, Cholesterol Ester Transfer Proteins, Diabetes Mellitus, Type 1, Treatment Outcome, Endocrinology, chemistry, biology.protein, Female, lipids (amino acids, peptides, and proteins), Cardiology and Cardiovascular Medicine, business, Plant lipid transfer proteins, Biomarkers

الوصف: Background and aims Cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP) are crucial proteins in reverse cholesterol transport. There are insufficient data on regulating these proteins by insulin therapy in type 1 diabetes mellitus (T1DM). We aimed to assess prospectively the impact of insulin therapy initiation on transfer proteins serum levels in adults with newly diagnosed T1DM. Methods and results 57 adults with newly diagnosed T1DM were enrolled in the InLipoDiab1 Study. All participants were treated with subcutaneous insulin in the model of intensive insulin therapy since the diagnosis of diabetes. Serum PLTP and CETP concentrations were measured at diagnosis, after three weeks, six months, and after one year of insulin treatment, using the immunoenzymatic method ELISA. A significant decrease in PLTP and CETP concentrations were demonstrated during twelve months of insulin therapy in newly diagnosed T1DM. The dynamics of changes in the level of these proteins varied depending on the occurrence of remission after a year of the disease. In the group without remission, a significant decrease in PLTP and CETP levels appeared after six months of follow-up. The remission group was characterized by a decrease in proteins concentration only after one year of treatment. In the non-remission group, significant negative correlations were found between the daily dose of insulin and levels of PLTP and CETP. Conclusion Exogenous insulin is an inhibitor of lipid transfer proteins involved in high-density lipoprotein cholesterol metabolism in the first year of treatment.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d227254b7b81ce95dcb9f369611a2c09Test
https://doi.org/10.1016/j.numecd.2020.11.006Test

المؤلفون: Nadir Kadri, Sarah J. Richardson, Lydia Sorokin, Eva Korpos, Sophie Loismann, Clais R. Findeisen, Noel G. Morgan, Alberto Pugliese, Frank Arfuso, George W. Burke, Marika Bogdani

المصدر: Diabetologia

مصطلحات موضوعية: 0301 basic medicine, Male, Pathology, Endocrinology, Diabetes and Metabolism, Autoimmunity, medicine.disease_cause, Mice, 0302 clinical medicine, Tertiary lymphoid organs, Mice, Inbred NOD, Child, NOD mice, Aged, 80 and over, Middle Aged, medicine.anatomical_structure, Type 1 diabetes, Fibroblastic reticular cells, Child, Preschool, Lymph node, Female, Beta cell, Adult, medicine.medical_specialty, Basement membrane, Adolescent, T cell, High endothelial venules, 030209 endocrinology & metabolism, Biology, Article, 03 medical and health sciences, Islets of Langerhans, Young Adult, Internal Medicine, medicine, Animals, Humans, Pancreas, B cell, Aged, Autoantibodies, Transplantation, medicine.disease, 030104 developmental biology, Diabetes Mellitus, Type 1, Tertiary Lymphoid Structures, Microscopy, Fluorescence, Reticular fibres, Insulitis

الوصف: Aims/hypothesis We and others previously reported the presence of tertiary lymphoid organs (TLOs) in the pancreas of NOD mice, where they play a role in the development of type 1 diabetes. Our aims here are to investigate whether TLOs are present in the pancreas of individuals with type 1 diabetes and to characterise their distinctive features, in comparison with TLOs present in NOD mouse pancreases, in order to interpret their functional significance. Methods Using immunofluorescence confocal microscopy, we examined the extracellular matrix (ECM) and cellular constituents of pancreatic TLOs from individuals with ongoing islet autoimmunity in three distinct clinical settings of type 1 diabetes: at risk of diabetes; at/after diagnosis; and in the transplanted pancreas with recurrent diabetes. Comparisons were made with TLOs from 14-week-old NOD mice, which contain islets exhibiting mild to heavy leucocyte infiltration. We determined the frequency of the TLOs in human type 1diabetes with insulitis and investigated the presence of TLOs in relation to age of onset, disease duration and disease severity. Results TLOs were identified in preclinical and clinical settings of human type 1 diabetes. The main characteristics of these TLOs, including the cellular and ECM composition of reticular fibres (RFs), the presence of high endothelial venules and immune cell subtypes detected, were similar to those observed for TLOs from NOD mouse pancreases. Among 21 donors with clinical type 1 diabetes who exhibited insulitis, 12 had TLOs and had developed disease at younger age compared with those lacking TLOs. Compartmentalised TLOs with distinct T cell and B cell zones were detected in donors with short disease duration. Overall, TLOs were mainly associated with insulin-containing islets and their frequency decreased with increasing severity of beta cell loss. Parallel studies in NOD mice further revealed some differences in so far as regulatory T cells were essentially absent from human pancreatic TLOs and CCL21 was not associated with RFs. Conclusions/interpretation We demonstrate a novel feature of pancreas pathology in type 1 diabetes. TLOs represent a potential site of autoreactive effector T cell generation in islet autoimmunity and our data from mouse and human tissues suggest that they disappear once the destructive process has run its course. Thus, TLOs may be important for type 1 diabetes progression. Graphical abstract

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f333af12269efbba20d5e0fefe7a11dfTest
http://europepmc.org/articles/PMC8187221Test