المؤلفون: Tomas Vaisar, Angela Irwin, Karin E. Bornfeldt, George L. King, Hetal Shah, Hillary A. Keenan, I-Hsien Wu, Carla J. Greenbaum, John Gauthier, Vanessa Bahnam, Jake Wimberger, Jay W. Heinecke, Emily Wolfson, Jenny E. Kanter

المصدر: Diabetes Care

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Time Factors, Lipoproteins, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Cohort Studies, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Pathophysiology/Complications, Aged, Advanced and Specialized Nursing, High concentration, Type 1 diabetes, biology, Aryldialkylphosphatase, business.industry, Cholesterol, Cholesterol, HDL, Paraoxonase, nutritional and metabolic diseases, Middle Aged, Atherosclerosis, medicine.disease, PON1, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Endocrinology, chemistry, biology.protein, Female, lipids (amino acids, peptides, and proteins), business, Diabetic Angiopathies, Ex vivo, Cohort study

الوصف: OBJECTIVE A subset of people with long-standing type 1 diabetes (T1D) appears to be protected from microvascular and macrovascular complications. Previous studies have focused on improved abilities to respond to glucose and its downstream effects as protective mechanisms. It is unclear whether lipoproteins play a role in the vascular health of these people. We therefore determined whether HDL particle concentration, size, function, and/or protein composition associate with protection from vascular complications. RESEARCH DESIGN AND METHODS We studied two independent cross-sectional cohorts with T1D: the T1D Exchange Living Biobank (n = 47) and the Joslin Medalist Study (n = 100). Some of the subjects had vascular complications, whereas others never exhibited vascular complications, despite an average duration of diabetes in the cohorts of 45 years. We assessed HDL particle size and concentration by calibrated ion mobility analysis, the HDL proteome by targeted mass spectrometry, and HDL function ex vivo by quantifying cholesterol efflux capacity and inhibition of monocyte adhesion to endothelial cells. RESULTS In both cohorts, people without vascular complications exhibited significantly higher concentrations of medium-sized HDL particles (M-HDL) independently of total and HDL cholesterol levels. While no consistent differences in HDL functions were observed ex vivo, people without vascular complications had higher levels of HDL-associated paraoxonase 1 (PON1), an enzyme that inhibits atherosclerosis in animal models. CONCLUSIONS Elevated concentrations of M-HDL particles and elevated levels of HDL-associated PON1 may contribute to long-term protection from the vascular complications of diabetes by pathways that are independent of total cholesterol and HDL cholesterol.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::897d83b3cf31d6798c5e128bc886384cTest
https://doi.org/10.2337/dc19-0772Test

المؤلفون: Helmut Hiller, Martha Campbell-Thompson, Clive Wasserfall, Irina Kusmartseva, Maria Beery, Stephen Selman, Amanda L. Posgai, Michael J. Haller, Desmond A. Schatz, Myriam Padilla, Harry S. Nick, Mark A. Atkinson

المصدر: Diabetes

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Time Factors, Adolescent, Trypsinogen, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Enteroendocrine cell, Pathophysiology, Glucagon, Gene Expression Regulation, Enzymologic, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Pregnancy, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Endocrine system, Amylase, Child, Pancreas, Aged, Autoantibodies, Type 1 diabetes, biology, Infant, Newborn, Infant, Middle Aged, medicine.disease, Diabetes Mellitus, Type 1, 030104 developmental biology, Endocrinology, chemistry, Case-Control Studies, Child, Preschool, Amylases, biology.protein, Female, Hormone

الوصف: Within the human pancreas, exocrine and endocrine cells control secretion of digestive enzymes and production of hormones to maintain metabolic homeostasis, respectively. While the vast majority of type 1 diabetes research efforts have focused on endocrine function and autoimmunity, recent studies identified a series of unique features (e.g., reduced weight and volume, increased density of leukocytes) within the exocrine pancreas in this disease, but the mechanisms underlying these aberrancies are unknown. Therefore, we histologically assessed amylase, insulin, glucagon, lipase, and/or trypsinogen in 78 organ donor pancreata from birth through adulthood in control subjects and those at various stages of type 1 diabetes. While amylase-positive (AMY(+)) acinar cells were detectable in pancreata from all study groups, tissues from individuals >2 years of age contained clusters of acinar cells devoid of amylase (AMY(−)). A majority of these AMY(−) cell clusters localized proximal to islets (i.e., peri-islet). Additionally, most AMY(−) clusters were positive for the exocrine enzymes lipase and trypsinogen. Interestingly, type 1 diabetes pancreata displayed significant reductions in the frequency of these AMY(−) cell clusters. These results support a contribution of the islet-acinar axis in pancreatic development and underscore a potential role for the exocrine pancreas in the pathogenesis of type 1 diabetes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::57ee15eadb145f865624fac8502f4b16Test
https://doi.org/10.2337/db19-0554Test

المؤلفون: Eleanor M, Scott, Denice S, Feig, Helen R, Murphy, Graham R, Law, Marlon, Pragnell

المصدر: Diabetes Care

مصطلحات موضوعية: Adult, Blood Glucose, medicine.medical_specialty, Time Factors, A300 Clinical Medicine, Adolescent, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Pregnancy in Diabetics, 030209 endocrinology & metabolism, Gestational Age, Glycemic Control, Fetal exposure, Fetal Macrosomia, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Insulin Infusion Systems, Computer Systems, Pregnancy, Internal medicine, Diabetes mellitus, Internal Medicine, Medicine, Humans, Insulin, 030212 general & internal medicine, Advanced and Specialized Nursing, Glycated Hemoglobin, Type 1 diabetes, business.industry, Continuous glucose monitoring, Blood Glucose Self-Monitoring, Self-Management, Infant, Newborn, Pregnancy Outcome, Clinical Care/Education/Nutrition/Psychosocial Research, Gestational age, medicine.disease, United Kingdom, Endocrinology, Diabetes Mellitus, Type 1, Equipment and Supplies, Gestation, Female, business

الوصف: OBJECTIVE To determine if temporal glucose profiles differed between 1) women who were randomized to real-time continuous glucose monitoring (RT-CGM) or self-monitored blood glucose (SMBG), 2) women who used insulin pumps or multiple daily insulin injections (MDIs), and 3) women whose infants were born large for gestational age (LGA) or not, by assessing CGM data obtained from the Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT). RESEARCH DESIGN AND METHODS Standard summary metrics and functional data analysis (FDA) were applied to CGM data from the CONCEPTT trial (RT-CGM, n = 100; SMBG, n = 100) taken at baseline and at 24- and 34-weeks’ gestation. Multivariable regression analysis determined if temporal differences in 24-h glucose profiles occurred between comparators in each of the three groups. RESULTS FDA revealed that women using RT-CGM had significantly lower glucose (0.4–0.8 mmol/L [7–14 mg/dL]) for 7 h/day (0800 h to 1200 h and 1600 h to 1900 h) compared with those with SMBG. Women using pumps had significantly higher glucose (0.4–0.9 mmol/L [7–16 mg/dL]) for 12 h/day (0300 h to 0600 h, 1300 h to 1800 h, and 2030 h to 0030 h) at 24 weeks with no difference at 34 weeks compared with MDI. Women who had an LGA infant ran a significantly higher glucose by 0.4–0.7 mmol/L (7–13 mg/dL) for 4.5 h/day at baseline, by 0.4–0.9 mmol/L (7–16 mg/dL) for 16 h/day at 24 weeks, and by 0.4–0.7 mmol/L (7–13 mg/dL) for 14 h/day at 34 weeks. CONCLUSIONS FDA of temporal glucose profiles gives important information about differences in glucose control and its timing, which are undetectable by standard summary metrics. Women using RT-CGM were able to achieve better daytime glucose control, reducing fetal exposure to maternal glucose.

وصف الملف: application/msword

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::85b015de0c1e4ed637dea753f55df7d1Test

المؤلفون: Linda A. DiMeglio, Carla J. Greenbaum, S. E. Gitelman, Wei Hao, David Boulware

المصدر: Diabetes Care

مصطلحات موضوعية: Adult, Male, Research design, medicine.medical_specialty, Time Factors, Adolescent, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Insulin-Secreting Cells, Internal medicine, Diabetes mellitus, Internal Medicine, Clinical endpoint, Humans, Hypoglycemic Agents, Insulin, Medicine, Young adult, Child, Randomized Controlled Trials as Topic, Glycated Hemoglobin, Advanced and Specialized Nursing, Type 1 diabetes, C-Peptide, Dose-Response Relationship, Drug, business.industry, C-peptide, Age Factors, Clinical Care/Education/Nutrition/Psychosocial Research, Middle Aged, medicine.disease, 3. Good health, Dose–response relationship, Diabetes Mellitus, Type 1, Endocrinology, chemistry, Child, Preschool, Female, business

الوصف: OBJECTIVE We aimed to describe the natural history of residual insulin secretion in Type 1 Diabetes TrialNet participants over 4 years from diagnosis and relate this to previously reported alternative clinical measures reflecting β-cell secretory function. RESEARCH DESIGN AND METHODS Data from 407 subjects from 5 TrialNet intervention studies were analyzed. All subjects had baseline stimulated C-peptide values of ≥0.2 nmol/L from mixed-meal tolerance tests (MMTTs). During semiannual visits, C-peptide values from MMTTs, HbA1c, and insulin doses were obtained. RESULTS The percentage of individuals with stimulated C-peptide of ≥0.2 nmol/L or detectable C-peptide of ≥0.017 nmol/L continued to diminish over 4 years; this was markedly influenced by age. At 4 years, only 5% maintained their baseline C-peptide secretion. The expected inverse relationships between C-peptide and HbA1c or insulin doses varied over time and with age. Combined clinical variables, such as insulin-dose adjusted HbA1c (IDAA1C) and the relationship of IDAA1C to C-peptide, also were influenced by age and time from diagnosis. Models using these clinical measures did not fully predict C-peptide responses. IDAA1C ≤9 underestimated the number of individuals with stimulated C-peptide ≥0.2 nmol/L, especially in children. CONCLUSIONS Current trials of disease-modifying therapy for type 1 diabetes should continue to use C-peptide as a primary end point of β-cell secretory function. Longer duration of follow-up is likely to provide stronger evidence of the effect of disease-modifying therapy on preservation of β-cell function.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dd43678c87959a86c1ac036aab8a4f22Test
https://doi.org/10.2337/dc16-0360Test

المؤلفون: Sartaj Sandhu, Natalie Bellini, Manav Batra, Husam Ghanim, Paresh Dandona, Aditya Mehta, Antoine Makdissi, Sandeep Dhindsa, Ajay Chaudhuri, Jeanne Hejna, Nitesh D. Kuhadiya, Kelly Green, Min Yang

المصدر: Diabetes Care

مصطلحات موضوعية: Adult, Blood Glucose, Male, medicine.medical_specialty, Time Factors, Emerging Technologies and Therapeutics, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Hypoglycemia, Placebo, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Weight loss, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Insulin, Obesity, Glycemic, Advanced and Specialized Nursing, Type 1 diabetes, Liraglutide, business.industry, Body Weight, Middle Aged, Overweight, Glucagon, Postprandial Period, medicine.disease, Diabetes Mellitus, Type 1, Treatment Outcome, Endocrinology, Drug Therapy, Combination, Female, medicine.symptom, business, medicine.drug

الوصف: OBJECTIVE To investigate whether addition of three different doses of liraglutide to insulin in patients with type 1 diabetes (T1D) results in significant reduction in glycemia, body weight, and insulin dose. RESEARCH DESIGN AND METHODS We randomized 72 patients (placebo = 18, liraglutide = 54) with T1D to receive placebo and 0.6, 1.2, and 1.8 mg liraglutide daily for 12 weeks. RESULTS In the 1.2-mg and 1.8-mg groups, the mean weekly reduction in average blood glucose was −0.55 ± 0.11 mmol/L (10 ± 2 mg/dL) and −0.55 ± 0.05 mmol/L (10 ± 1 mg/dL), respectively (P < 0.0001), while it remained unchanged in the 0.6-mg and placebo groups. In the 1.2-mg group, HbA1c fell significantly (−0.78 ± 15%, −8.5 ± 1.6 mmol/mol, P < 0.01), while it did not in the 1.8-mg group (−0.42 ± 0.15%, −4.6 ± 1.6 mmol/mol, P = 0.39) and 0.6-mg group (−0.26 ± 0.17%, −2.8 ± 1.9 mmol/mol, P = 0.81) vs. the placebo group (−0.3 ± 0.15%, −3.3 ± 1.6 mmol/mol). Glycemic variability was reduced by 5 ± 1% (P < 0.01) in the 1.2-mg group only. Total daily insulin dose fell significantly only in the 1.2-mg and 1.8-mg groups (P < 0.05). There was a 5 ± 1 kg weight loss in the two higher-dose groups (P < 0.05) and by 2.7 ± 0.6 kg (P < 0.01) in the 0.6-mg group vs. none in the placebo group. In the 1.2- and 1.8-mg groups, postprandial plasma glucagon concentration fell by 72 ± 12% and 47 ± 12%, respectively (P < 0.05). Liraglutide led to higher gastrointestinal adverse events (P < 0.05) and ≤1% increases (not significant) in percent time spent in hypoglycemia ( CONCLUSIONS Addition of 1.2 mg and 1.8 mg liraglutide to insulin over a 12-week period in overweight and obese patients with T1D results in modest reductions of weekly mean glucose levels with significant weight loss, small insulin dose reductions, and frequent gastrointestinal side effects. These findings do not justify the use of liraglutide in all patients with T1D.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ae728c6d6ff482987b81e22e3615fa2cTest
https://doi.org/10.2337/dc15-1136Test

المؤلفون: Natalia O. Dmitrieva, Lisa K. Honeycutt, Richard S. Surwit, Jennifer Kuo, Mark N. Feinglos, Ashley A. Moskovich, James D. Lane, Rhonda M. Merwin, Nancy Zucker

المصدر: Diabetes Care

مصطلحات موضوعية: Adult, Male, Research design, medicine.medical_specialty, Time Factors, Adolescent, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Emotions, 030209 endocrinology & metabolism, Anxiety, Medication Adherence, Feeding and Eating Disorders, Eating, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Diabetes management, Weight loss, Surveys and Questionnaires, Internal medicine, Diabetes mellitus, Weight Loss, Internal Medicine, medicine, Humans, Insulin, 030212 general & internal medicine, Aged, Advanced and Specialized Nursing, Type 1 diabetes, Dose-Response Relationship, Drug, business.industry, Body Weight, Clinical Care/Education/Nutrition/Psychosocial Research, Middle Aged, medicine.disease, Disgust, 3. Good health, Diabetes Mellitus, Type 1, Endocrinology, Female, medicine.symptom, business, Clinical psychology

الوصف: OBJECTIVE Individuals with type 1 diabetes who restrict insulin to control weight are at high risk for diabetes-related complications and premature death. However, little is known about this behavior or how to effectively intervene. The aim of the current study was to identify predictors of insulin restriction in the natural environment that might inform new treatment directions. RESEARCH DESIGN AND METHODS Eighty-three adults with type 1 diabetes and a range of eating disorder symptomatology completed 3 days of ecological momentary assessment. Participants reported emotions, eating, and insulin dosing throughout the day using their cellular telephone. Linear mixed models were used to estimate the effects of heightened negative affect (e.g., anxiety) before eating and characteristics of the eating episode (e.g., eating a large amount of food) on the risk of insulin restriction. RESULTS Individuals who reported greater-than-average negative affect (general negative affect and negative affect specifically about diabetes) during the study period were more likely to restrict insulin. Momentary increases in anxiety/nervousness and guilt/disgust with self before eating (relative to an individual’s typical level) further increased the odds of restricting insulin at the upcoming meal. Insulin restriction was more likely when individuals reported that they broke a dietary rule (e.g., “no desserts”). CONCLUSIONS Results suggest that insulin restriction might be decreased by helping patients with type 1 diabetes respond effectively to heightened negative affect (e.g., anxiety, guilt) and encouraging patients to take a less rigid, punitive approach to diabetes management.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8de4c692cd989031ba7b353384425668Test
https://doi.org/10.2337/dc15-0753Test

المؤلفون: Linda A. DiMeglio, C. Max Schmidt, Santica Marcovina, Adam C. Swensen, Teresa L. Mastracci, Cate Speake, Wei-Jun Qian, Henry T. Bahnson, Lian Yi, Carla J. Greenbaum, Julius O. Nyalwidhe, Peter Arvan, Raghavendra G. Mirmira, Robert V. Considine, Carmella Evans-Molina, Janice S. Blum, Leena Haataja, Asa K. Davis, Jerry L. Nadler, Margaret A. Morris, Michele T. Yip-Schneider, Emily K. Sims

المصدر: Diabetes Care

مصطلحات موضوعية: Adult, Male, endocrine system, medicine.medical_specialty, Time Factors, Adolescent, endocrine system diseases, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Cohort Studies, Young Adult, chemistry.chemical_compound, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Insulin, Meals, Proinsulin, Advanced and Specialized Nursing, Type 1 diabetes, e-Letters: Comments and Responses, C-Peptide, medicine.diagnostic_test, C-peptide, business.industry, Radioimmunoassay, Fasting, Middle Aged, medicine.disease, Titer, Diabetes Mellitus, Type 1, Endocrinology, chemistry, Immunoassay, Female, business

الوصف: In a cohort of 319 individuals with long-duration type 1 diabetes (T1D), we found that 89.9% of participants with undetectable stimulated C-peptide had measurable fasting or stimulated serum proinsulin (1). To ensure the validity of our results, we performed rigorous validation of the Millipore human intact and Des (31,32) proinsulin radioimmunoassay that included spike-in experiments using insulin, C-peptide, and proinsulin; independent calculation of a lower limit of detection; assessment of inter- and intra-assay coefficients of variation; analysis of linearity of dilution; analysis of samples pre- and postpancreatectomy; analysis of effects of increased insulin autoantibody titers; and quantitative validation of our findings using mass spectrometry (1). The letter by Steenkamp et al. (2) in response to our article suggests the Millipore assay may overestimate proinsulin levels compared with the ALPCO STELLUX human total proinsulin ELISA. The authors’ concerns are based on their finding that, using the ALPCO assay, proinsulin was detected in only 16% of random samples from a smaller subset of C-peptide–negative individuals from the same T1D Exchange Residual C-peptide Study (3). Quantitative immunoassay performance differences between different assay platforms are not surprising due to antibody interactions with different epitopes on native antigens …

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2bfb99cd84092d034ab127337af85728Test
https://doi.org/10.2337/dci19-0012Test

المؤلفون: Frans Gorus, Katrijn Verhaeghen, Janet M. Wenzlau, Bart Keymeulen, Simke Demeester, Leonard Kaufman, Annelien Van Dalem, Ilse Weets, Eric V. Balti, Howard W. Davidson, Ursule Van de Velde, Patrick Goubert, Daniel Pipeleers

المساهمون: Medical Biochemistry, Pathologic Biochemistry and Physiology, Public Health Care, Pathology/molecular and cellular medicine, Vriendenkring VUB, Biostatistics and medical informatics, Diabetes Pathology & Therapy

المصدر: Diabetes Care

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Time Factors, Adolescent, Emerging Technologies and Therapeutics, type 1 diabetes, Insulin Antibodies, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Antibodies, Monoclonal, Humanized, Placebo, Otelixizumab, Young Adult, Insulin-Secreting Cells, Internal medicine, Diabetes mellitus, Internal Medicine, Humans, Insulin, Medicine, Child, Advanced and Specialized Nursing, Type 1 diabetes, business.industry, Area under the curve, Autoantibody, Prognosis, medicine.disease, 3. Good health, Diabetes Mellitus, Type 1, Treatment Outcome, Endocrinology, Female, Radiobinding assay, business, Biomarkers, medicine.drug

الوصف: OBJECTIVE Immune intervention trials in recent-onset type 1 diabetes would benefit from biomarkers associated with good therapeutic response. In the previously reported randomized placebo-controlled anti-CD3 study (otelixizumab; GlaxoSmithKline), we tested the hypothesis that specific diabetes autoantibodies might serve this purpose. RESEARCH DESIGN AND METHODS In the included patients (n = 40 otelixizumab, n = 40 placebo), β-cell function was assessed as area under the curve (AUC) C-peptide release during a hyperglycemic glucose clamp at baseline (median duration of insulin treatment: 6 days) and every 6 months until 18 months after randomization. (Auto)antibodies against insulin (I[A]A), GAD (GADA), IA-2 (IA-2A), and ZnT8 (ZnT8A) were determined on stored sera by liquid-phase radiobinding assay. RESULTS At baseline, only better preserved AUC C-peptide release and higher levels of IAA were associated with better preservation of β-cell function and lower insulin needs under anti-CD3 treatment. In multivariate analysis, IAA (P = 0.022) or the interaction of IAA and C-peptide (P = 0.013) independently predicted outcome together with treatment. During follow-up, good responders to anti-CD3 treatment (i.e., IAA+ participants with relatively preserved β-cell function [≥25% of healthy control subjects]) experienced a less pronounced insulin-induced rise in I(A)A and lower insulin needs. GADA, IA-2A, and ZnT8A levels were not influenced by anti-CD3 treatment, and their changes showed no relation to functional outcome. CONCLUSIONS There is important specificity of IAA among other diabetes autoantibodies to predict good therapeutic response of recent-onset type 1 diabetic patients to anti-CD3 treatment. If confirmed, future immune intervention trials in type 1 diabetes should consider both relatively preserved functional β-cell mass and presence of IAA as inclusion criteria.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::074451f625b9be61ec8e27ad76f59c4eTest
https://doi.org/10.2337/dc14-1575Test

المؤلفون: Richard A, Oram, Timothy J, McDonald, Beverley M, Shields, Michelle M, Hudson, Maggie H, Shepherd, Suzanne, Hammersley, Ewan R, Pearson, Andrew T, Hattersley, Sian, Ellard

المصدر: Diabetes Care. 38:323-328

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Time Factors, Cross-sectional study, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Population, 030209 endocrinology & metabolism, Hypoglycemia, Article, Young Adult, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Interquartile range, Internal medicine, Diabetes mellitus, Insulin Secretion, Internal Medicine, medicine, Humans, Insulin, Child, education, 030304 developmental biology, Advanced and Specialized Nursing, 0303 health sciences, Type 1 diabetes, education.field_of_study, C-Peptide, C-peptide, business.industry, Postprandial Period, medicine.disease, 3. Good health, Cross-Sectional Studies, Diabetes Mellitus, Type 1, Endocrinology, chemistry, Creatinine, Female, business

الوصف: OBJECTIVE Small studies using ultrasensitive C-peptide assays suggest endogenous insulin secretion is frequently detectable in patients with long-standing type 1 diabetes (T1D), but these studies do not use representative samples. We aimed to use the stimulated urine C-peptide-to-creatinine ratio (UCPCR) to assess C-peptide levels in a large cross-sectional, population-based study of patients with T1D. RESEARCH DESIGN AND METHODS We recruited 924 patients from primary and secondary care in two U.K. centers who had a clinical diagnosis of T1D, were under 30 years of age when they received a diagnosis, and had a diabetes duration of >5 years. The median age at diagnosis was 11 years (interquartile range 6–17 years), and the duration of diabetes was 19 years (11–27 years). All provided a home postmeal UCPCR, which was measured using a Roche electrochemiluminescence assay. RESULTS Eighty percent of patients (740 of 924 patients) had detectable endogenous C-peptide levels (UCPCR >0.001 nmol/mmol). Most patients (52%, 483 of 924 patients) had historically very low undetectable levels (UCPCR 0.0013–0.03 nmol/mmol); 8% of patients (70 of 924 patients) had a UCPCR ≥0.2 nmol/mmol, equivalent to serum levels associated with reduced complications and hypoglycemia. Absolute UCPCR levels fell with duration of disease. Age at diagnosis and duration of disease were independent predictors of C-peptide level in multivariate modeling. CONCLUSIONS This population-based study shows that the majority of long-duration T1D patients have detectable urine C-peptide levels. While the majority of patients are insulin microsecretors, some maintain clinically relevant endogenous insulin secretion for many years after the diagnosis of diabetes. Understanding this may lead to a better understanding of pathogenesis in T1D and open new possibilities for treatment.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8b1e1da4ea6bfedff3a0c99a4fd33862Test
https://doi.org/10.2337/dc14-0871Test

المؤلفون: Maciej T. Malecki, Josyf C. Mychaleckyj, Andrzej T. Galecki, Andrzej S. Krolewski, Tomohito Gohda, James H. Warram, Monika A. Niewczas, Jan Skupien

المصدر: Diabetes Care

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Time Factors, Endocrinology, Diabetes and Metabolism, Urology, Renal function, urologic and male genital diseases, Kidney Function Tests, chemistry.chemical_compound, Internal medicine, Diabetes mellitus, Internal Medicine, Humans, Receptors, Tumor Necrosis Factor, Type II, Medicine, Longitudinal Studies, Pathophysiology/Complications, Glycated Hemoglobin, Advanced and Specialized Nursing, Creatinine, Type 1 diabetes, Proteinuria, business.industry, Drug Synergism, Prognosis, medicine.disease, 3. Good health, Diabetes Mellitus, Type 1, Endocrinology, chemistry, Kidney Failure, Chronic, Female, Glycated hemoglobin, Tumor necrosis factor receptor 2, medicine.symptom, business, Biomarkers, Follow-Up Studies, Glomerular Filtration Rate, Kidney disease

الوصف: OBJECTIVE We studied the serum concentration of tumor necrosis factor receptor 2 (TNFR2) and the rate of renal decline, a measure of the intensity of the disease process leading to end-stage renal disease (ESRD). RESEARCH DESIGN AND METHODS A cohort of 349 type 1 diabetic patients with proteinuria was followed for 5–18 years. Serum TNFR2, glycated hemoglobin A1c (HbA1c), and other characteristics were measured at enrollment. We used a novel analytic approach, a joint longitudinal-survival model, fitted to serial estimates of glomerular filtration rate (eGFR) based on serum creatinine (median seven per patient) and time to onset of ESRD (112 patients) to estimate the rate of renal decline (eGFR loss). RESULTS At enrollment, all patients had chronic kidney disease stage 1–3. The mean (±SD) rate of eGFR loss during 5–18 years of follow-up was −5.2 (±4.9) mL/min/1.73 m2/year. Serum TNFR2 was the strongest determinant of renal decline and ESRD risk (C-index 0.79). The rate of eGFR loss became steeper with rising concentration of TNFR2, and elevated HbA1c augmented the strength of this association (P = 0.030 for interaction). In patients with HbA1c ≥10.1% (87 mmol/mol), the difference in the rate of eGFR loss between the first and fourth quartiles of TNFR2 was 5.4 mL/min/1.73 m2/year, whereas it was only 1.9 in those with HbA1c CONCLUSIONS Circulating TNFR2 is a major determinant of renal decline in patients with type 1 diabetes and proteinuria. Elevated HbA1c magnifies its effect. Although the mechanisms of this synergism are unknown, our findings allow us to stratify patients according to risk of ESRD.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::da1780fc9b125d9a65d701081e222ab4Test
https://doi.org/10.2337/dc13-1983Test