Abstract：
:Available evidence provides arguments both for and against a primary pathogenic role for T cells in human type 1 diabetes. Genetic susceptibility linked to HLA Class II lends strong support. Histopathology documents HLA Class I hyperexpression and islet infiltrates dominated by CD8+ T cells. While both hallmarks are near absent in autoantibody-positive donors, the variable insulitis and residual beta cells of recent-onset donors suggests the existence of a younger-onset endotype with more aggressive autoimmunity and an older-onset endotype with more vulnerable beta cells. Functional arguments from ex vivo and in vitro human studies and in vivo 'humanised' mouse models are instead neutral or against a T cell role. Clinical support is provided by the appearance of islet autoantibodies before disease onset. The faster C-peptide loss and superior benefits of immunotherapies in individuals with younger-onset type 1 diabetes reinforce the view of age-related endotypes. Clarifying the relative role of T cells will require technical advances in the identification of their target antigens, in their detection and phenotyping in the blood and pancreas, and in the study of the T cell/beta cell crosstalk. Critical steps toward this goal include the understanding of the link with environmental triggers, the description of T cell changes along the natural history of disease, and their relationship with age and the 'benign' islet autoimmunity of healthy individuals. Graphical abstract.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Carré A,Richardson SJ,Larger E,Mallone Rdoi
10.1007/s00125-020-05298-ysubject
Has Abstractpub_date
2021-01-01 00:00:00pages
15-25issue
1eissn
0012-186Xissn
1432-0428pii
10.1007/s00125-020-05298-yjournal_volume
64pub_type
杂志文章,评审相关文献
DIABETOLOGIA文献大全abstract：:People with type 2 diabetes have an increased risk of cardiovascular disease (CVD). Multivariate cardiovascular risk scores have been used in many countries to identify individuals who are at high risk of CVD. These risk scores include those originally developed in individuals with diabetes and those developed in a ge...
journal_title：Diabetologia
pub_type： 杂志文章,评审
doi：10.1007/s00125-009-1454-0
更新日期：2009-10-01 00:00:00
abstract：AIMS/HYPOTHESIS:We investigated spinal and peripheral kappa opioid systems in diabetic rats. MATERIALS AND METHODS:Dynorphin A, N-methyl-D-aspartate (NMDA) and kappa opioid receptor (KOR) were measured in spinal cord, dorsal root ganglia, peripheral nerves and foot skin of control and streptozotocin-induced diabetic r...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-006-0397-y
更新日期：2006-11-01 00:00:00
abstract：AIMS/HYPOTHESIS:The aim of this work was to examine the progression to type 1 and type 2 diabetes after gestational diabetes mellitus (GDM) in a 23 year follow-up study. METHODS:We carried out a cohort study of 391 women with GDM diagnosed by an OGTT or the use of insulin treatment during pregnancy, and 391 age- and p...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-020-05215-3
更新日期：2020-10-01 00:00:00
abstract：AIMS:This prospective case-control study aimed at evaluating the time course of serum concentrations of soluble adhesion molecules; intercellular adhesion molecule-1 and L-selectin in siblings with signs of pre-clinical Type 1 diabetes in order to relate these concentrations to autoantibody status and to assess whether...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-003-1072-1
更新日期：2003-04-01 00:00:00
abstract：:To evaluate the behaviour and predictive value of islet cell and insulin autoantibodies in patients with organ-specific autoimmune diseases, we followed 21 non-diabetic subjects for a mean period of 84 +/- 27 months. Ten patients were persistently seropositive for complement-fixing islet cell antibodies and high titre...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00299020
更新日期：1987-05-01 00:00:00
abstract：:New treatment strategies for subjects with Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus are being developed. Pilot studies utilising insulin itself have been reported to prevent Type 1 diabetes in subjects likely, by immunogenetic and physiologic criteria, to develop clinically overt...
journal_title：Diabetologia
pub_type： 杂志文章,评审
doi：10.1007/BF00586274
更新日期：1992-12-01 00:00:00
abstract：AIMS/HYPOTHESIS:The SMXA-5 mouse is one of the SMXA recombinant inbred substrains established from the non-diabetic SM/J and A/J strains, and is a model for polygenic type 2 diabetes, characterised by moderately impaired glucose tolerance and hyperinsulinaemia. These diabetic traits are worsened by feeding a high-fat d...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-005-0121-3
更新日期：2006-03-01 00:00:00
abstract：AIMS/HYPOTHESIS:Several investigations have shown that the renal medulla has a greater capacity to generate nitric oxide than the renal cortex. To further evaluate the changes of nitric oxide synthesis in the kidney, particularly in the outer medulla, in disorders involving fluid and electrolyte imbalances, we sought t...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s001250051354
更新日期：2000-05-01 00:00:00
abstract：AIMS/HYPOTHESIS:Type I (insulin-dependent) diabetes mellitus is characterised by leucocyte infiltration of pancreatic islets and a progressive destruction of insulin-producing beta cells. As endothelial nitric oxide production is known to regulate adhesion molecule expression and leucocyte permeation, we examined the a...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s001250051179
更新日期：1999-04-01 00:00:00
abstract：:The evolution of glucose assay methods has been central to the development of present therapies for diabetes mellitus. However, new blood glucose assay capabilities, such as convenient and truly continuous monitoring, are now needed to foster a new era of close blood glucose control. The principles and present status ...
journal_title：Diabetologia
pub_type： 杂志文章,评审
doi：10.1007/s001250051418
更新日期：1997-07-01 00:00:00
abstract：:Downregulation of insulin receptor tyrosine kinase (IRK) activity yields to impaired insulin signalling and contributes to the pathogenesis of cellular insulin resistance. Activation of protein kinase C (PKC) by different agents is associated with an inhibition of IRK activity in various cell types. There is evidence ...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s001250050761
更新日期：1997-07-01 00:00:00
abstract：:Glycation of long-lived proteins is an inevitable consequence of aging that is accelerated in patients with diabetes mellitus. Treatment of demineralized bone matrix particles from 35-week-old normal Long-Evans rats with glycoaldehyde, a precursor of advanced glycation end-products, was used to assess the effects of b...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00400353
更新日期：1993-09-01 00:00:00
abstract：AIMS/HYPOTHESIS:Several publications suggest an association between certain types of insulin and cancer, but with conflicting results. We investigated whether insulin glargine (A21Gly,B31Arg,B32Arg human insulin) is associated with an increased risk of cancer in a large population-based cohort study. METHODS:Data for ...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-011-2312-4
更新日期：2012-01-01 00:00:00
abstract：:The validity of the new diagnostic criteria for diabetes mellitus for Japanese subjects was assessed by the long-term prognosis of 501 patients, found in an epidemiological survey of 6,681 people in a Japanese town. Ten-year relative survival rates were examined in relation to the 50 g oral glucose tolerance test (ser...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00252627
更新日期：1981-03-01 00:00:00
abstract：AIMS/HYPOTHESIS:Several risk stratification systems have been proposed for predicting development of diabetic foot ulcer. However, little has been published that assesses their similarities and disparities, diagnostic accuracy and evidence level. Consequently, we conducted a systematic review of the existing stratifica...
journal_title：Diabetologia
pub_type： 杂志文章,评审
doi：10.1007/s00125-010-2030-3
更新日期：2011-05-01 00:00:00
abstract：:In perifused pancreatic islets, the fluorescence of oxidized flavoproteins (FAD) was recorded continuously. Elevation of glucose concentration in the medium form 0 or 5 mM to 20 mM led to decrease in FAD-fluorescence beginning 10 sec after change of medium. L-leucine (10 mM), (+/-)-B-BCH (20 mM) and alpha-ketoisocapro...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF01222108
更新日期：1975-12-01 00:00:00
abstract：AIMS/HYPOTHESIS:Non-alcoholic fatty liver disease (NAFLD) is common in type 2 diabetes but it is unknown whether NAFLD is prevalent in European women at risk of type 2 diabetes. We studied the prevalence of, and risk factors for, NAFLD in European women with previous gestational diabetes (GDM) at high risk of type 2 di...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-010-2009-0
更新日期：2011-03-01 00:00:00
abstract：:In postnatal organisms, insulin is well known as an essential anabolic hormone responsible for maintaining glucose homeostasis. Its biosynthesis by the pancreatic beta cell has been considered a model of tissue-specific gene expression. However, proinsulin mRNA and protein have been found in embryonic stages before th...
journal_title：Diabetologia
pub_type： 杂志文章,评审
doi：10.1007/s00125-006-0232-5
更新日期：2006-06-01 00:00:00
abstract：:It has been proposed that the development of diabetic complications may involve a depletion of cellular myo-inositol due to an increase in polyol (sorbitol) formation. We therefore initially examined the effect of diabetes on levels of these metabolites in isolated cerebral microvessels. Compared with microvessels fro...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00274782
更新日期：1988-10-01 00:00:00
abstract：:Insulin secretion rates after glucose loading were calculated from peripheral venous IRI concentrations considering half life and distribution space of exogenous insulin in normal men and dogs. The coefficients of multiple linear regression analysis between insulin secretion rates and plasma glucose (level and order a...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00290484
更新日期：1980-01-01 00:00:00
abstract：:A radioreceptor-assay for glucagon was developed employing pig liver plasma membranes isolated by means of an aqueous two-phase polymer system. The assay is simple, precise, and has a detection limit of 40 pg/ml. Acid-ethanol extracts of porcine intestinal mucosa and entero-glucagon purified by affinity chromatography...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00422324
更新日期：1975-06-01 00:00:00
abstract：AIMS/HYPOTHESIS:Osmotic and oxidative stress is associated with the progression and advancement of diabetic cataract. In the present study, we used a cDNA microarray method to analyse gene expression patterns in streptozotocin-induced diabetic rats and galactose-fed cataractous lenses. In addition, we investigated the ...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-005-1687-5
更新日期：2005-04-01 00:00:00
abstract：AIMS/HYPOTHESIS:Beta cells situated in the islet of Langerhans respond more vigorously to glucose than do dissociated beta cells. Mechanisms for this discrepancy were studied by comparing insulin-producing MIN6 cells aggregated into pseudoislets with MIN6 monolayer cells and mouse and human islets. METHODS:MIN6 monola...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-013-2903-3
更新日期：2013-07-01 00:00:00
abstract：AIMS/HYPOTHESIS:The UK Prospective Diabetes Study (UKPDS) risk engine has become a standard for cardiovascular risk assessment in type 2 diabetes mellitus. Skin autofluorescence was recently introduced as an alternative tool for cardiovascular risk assessment in diabetes. We investigated the prognostic value of skin au...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-009-1308-9
更新日期：2009-05-01 00:00:00
abstract：:The eyes, kidneys and pancreas of mice (SJL/J) infected with encephalomyocarditis virus were examined by light and electron microscopy. Diabetic mice with the longest duration (6 months) of diabetes showed marked renal and ocular alterations. Fasting blood glucose levels were 17.8-21.9 mmol/l and glycosuria was presen...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00282717
更新日期：1983-04-01 00:00:00
abstract：AIMS/HYPOTHESIS:No previous studies on the association between salt intake and the risk of type 2 diabetes have been reported. The aim of this study was to assess whether high salt intake, measured by 24-h urinary sodium excretion, is an independent risk factor for type 2 diabetes. METHODS:We followed prospectively 93...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-005-1824-1
更新日期：2005-08-01 00:00:00
abstract：AIMS/HYPOTHESIS:Obesity is a major risk factor for type 2 diabetes. Recent genome-wide association (GWA) studies have identified multiple loci robustly associated with BMI and risk of obesity. However, information on their associations with type 2 diabetes is limited. Such information could help increase our understand...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-011-2044-5
更新日期：2011-04-01 00:00:00
abstract：AIMS/HYPOTHESIS:Perinatal exposure to bisphenol A (BPA), a widely distributed environmental endocrine disruptor, is associated with insulin resistance and diabetes in offspring. The underlying molecular mechanisms could involve epigenetics, as adverse effects induced by environmental exposure in early life are suggeste...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-013-2944-7
更新日期：2013-09-01 00:00:00
abstract：:Use of monoclonal antibodies specific for rat lymphocyte subsets and an anti-insulin marker has allowed us to document the following sequence of events leading to the development of clinical diabetes in this animal model. The first change observed in the pancreas is increased expression of MHC class II molecules on va...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00280892
更新日期：1985-07-01 00:00:00
abstract：AIMS/HYPOTHESIS:Mitochondrial oxidative phosphorylation (OXPHOS) plays an important role in the pathophysiology of type 2 diabetes. Genes involved in OXPHOS have been reported to be down-regulated in skeletal muscle from patients with type 2 diabetes; however, hepatic regulation is unknown. MATERIALS AND METHODS:We an...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-006-0489-8
更新日期：2007-02-01 00:00:00
