Abstract：
AIMS/HYPOTHESIS:The study aimed to assess, in multiple populations, the role of HLA alleles on early and late age at onset of type 1 diabetes. METHODS:Stepwise linear regression models were used to determine which HLA class I and class II risk alleles to include. High-resolution genotyping data for patients from the Type 1 Diabetes Genetics Consortium (T1DGC) collection (n = 2,278) and four independent cohorts from Denmark, Sardinia and the USA (Human Biological Data Interchange [HBDI] and Joslin Diabetes Center) (n = 1,324) (total n = 3,602) were used to assess the role of HLA variation on age of onset and predict early onset (age ≤ 5 years) and late onset (age ≥ 15 years) of type 1 diabetes. RESULTS:In addition to carriage of HLA class I alleles A*24:02, B*39:06, B*44:03 and B*18:01, HLA class II DRB1-DQB1 loci significantly contributed to age at onset, explaining 3.4% of its variance in the combined data. HLA genotypes, together with sex, were able to predict late onset in all cohorts studied, with AUC values ranging from 0.58 to 0.63. Similar AUC values (0.59-0.70) were obtained for early onset for most cohorts, except in the Sardinian study, in which none of the models tested had significant predictive power. CONCLUSIONS/INTERPRETATION:HLA associations with age of onset are consistent across most white populations and HLA information can predict some of the risk of early and late onset of type 1 diabetes. Considerable heterogeneity was observed between Sardinian and other populations, particularly with regard to early age of onset.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Valdes AM,Erlich HA,Carlson J,Varney M,Moonsamy PV,Noble JAdoi
10.1007/s00125-012-2608-zsubject
Has Abstractpub_date
2012-09-01 00:00:00pages
2394-401issue
9eissn
0012-186Xissn
1432-0428journal_volume
55pub_type
杂志文章相关文献
DIABETOLOGIA文献大全abstract：AIMS/HYPOTHESIS:The workplace is a potentially important arena for prevention of type 2 diabetes and the first step is to identify occupations where the disease is common and/or risk is high. Therefore, our aim was to analyse incidence and prevalence of type 2 diabetes across all occupational groups in Sweden. METHODS...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-019-04997-5
更新日期：2020-01-01 00:00:00
abstract：AIMS/HYPOTHESIS:Type 2 diabetes mellitus is associated with reduced incretin effects. Although previous studies have shown that hyperglycaemia contributes to impaired incretin responses in beta cells, it is largely unknown how hyperlipidaemia, another feature of type 2 diabetes, contributes to impaired glucagon-like pe...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-012-2776-x
更新日期：2013-02-01 00:00:00
abstract：AIMS/HYPOTHESIS:Oxidized LDL is immunogenic and immune complexes formed by oxidized LDL and corresponding antibodies are pro-atherogenic and pro-inflammatory. Considering that macroalbuminuria is a risk factor for coronary heart disease and that common pathogenic factors for atherosclerosis and glomerulosclerosis exist...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-002-0962-y
更新日期：2002-11-01 00:00:00
abstract：AIMS/HYPOTHESIS:Diabetic retinopathy is characterised by morphological lesions related to disturbances in retinal blood flow. It has previously been shown that the early development of retinal lesions temporal to the fovea may predict the development of treatment-requiring diabetic maculopathy. The aim of this study wa...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-017-4424-y
更新日期：2017-12-01 00:00:00
abstract：:Cytokines could contribute to beta-cell damage in Type I diabetes mellitus. The radical nitric oxide, generated by the inducible form of nitric oxide synthase (iNOS), is a potential mediator of cytokine-induced beta-cell dysfunction. In rat pancreatic islets and insulin-producing cell lines, interleukin-1beta (IL-1bet...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s001250051036
更新日期：1998-09-01 00:00:00
abstract：:Forearm perfusion studies were carried out to determine the responsiveness to insulin of the superficial forearm tissues in non-obese Type 2 (non-insulin-dependent) diabetics, and the interrelationships among plasma concentrations of glucose, insulin and non-esterified fatty acids (NEFA), tissue uptake of glucose and ...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00281298
更新日期：1982-04-01 00:00:00
abstract：AIMS/HYPOTHESIS:This study aimed to elucidate the mechanism of increased proliferation of alpha cells in recent-onset type 1 diabetes. Pancreatic beta cells express GAD and produce γ-aminobutyric acid (GABA), which inhibits alpha cell secretion of glucagon. We explored the roles of GABA in alpha cell proliferation in c...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-017-4239-x
更新日期：2017-06-01 00:00:00
abstract：AIMS/HYPOTHESIS:High levels of cardiorespiratory fitness (CRF) and physical activity (PA) are associated with a favourable metabolic risk profile. However, there has been no thorough exploration of the independent contributions of cardiorespiratory fitness and subcomponents of activity (total PA, time spent sedentary, ...
journal_title：Diabetologia
pub_type： 杂志文章,多中心研究
doi：10.1007/s00125-007-0762-5
更新日期：2007-09-01 00:00:00
abstract：AIMS/HYPOTHESIS:The aim was to conduct a systematic review and meta-analysis of randomised controlled clinical trials assessing the effect of probiotic, prebiotic or synbiotic supplementation on gut microbiota and glucose control and lipid levels in individuals with diabetes. METHODS:MEDLINE, EMBASE and the Cochrane L...
journal_title：Diabetologia
pub_type： 杂志文章,评审
doi：10.1007/s00125-020-05295-1
更新日期：2021-01-01 00:00:00
abstract：:Urinary albumin excretion has been assessed in 585 newly-presenting Type 2 (non-insulin-dependent) diabetic patients (aged 53 (8) years, 67% male) at diagnosis with fasting plasma glucose 10.3 (3.2) mmol/l and over 3 years of dietary treatment. Urinary albumin at diagnosis, geometric mean (1 SD interval) corrected for...
journal_title：Diabetologia
pub_type： 杂志文章
doi：
更新日期：1993-10-01 00:00:00
abstract：:We compared urinary albumin excretion during and after pregnancy in 30 insulin-dependent diabetic (IDDM) women with normoalbuminuria and in 12 IDDM women with microalbuminuria (> 15 micrograms.min-1) prior to conception. There was a 6.7-fold increase in the urinary albumin excretion up until the third trimester in the...
journal_title：Diabetologia
pub_type： 临床试验,杂志文章
doi：10.1007/BF00400946
更新日期：1994-09-01 00:00:00
abstract：AIMS/HYPOTHESIS:In the light of a report suggesting that insulin glargine may increase cancer occurrence, the EASD asked us to perform this study. METHODS:We followed 114,841 individuals who had a prescription dispensed for insulin between 1 July and 31 December 2005. From 1 January 2006 to 31 December 2007, we noted ...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-009-1444-2
更新日期：2009-09-01 00:00:00
abstract：:Insulin secretion from pancreatic beta cells is dependent on membrane potential changes that result from the concerted regulation of multiple ion channels. Among the distinct K+ channels known to be expressed in beta cells, large conductance Ca(2+)-activated K+ channels have been suggested to play an important role in...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00403907
更新日期：1996-08-01 00:00:00
abstract：AIMS/HYPOTHESIS:Peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1 (PPARGC1), a coactivator regulating the transcription of genes involved in oxidative metabolism, is downregulated in patients with type 2 diabetes and in their first-degree relatives. Whether this downregulation is a cause or effect o...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-006-0369-2
更新日期：2006-10-01 00:00:00
abstract：:Restriction fragment length polymorphism of the human insulin receptor gene was analyzed with a 4.2 Kb cDNA probe in Japanese normal subjects and Type 2 (non-insulin-dependent) diabetic patients. Restriction endonuclease Rsa I digestion showed polymorphism of the human insulin receptor gene, with a band at 6.7 Kb, 6.2...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00869268
更新日期：1986-09-01 00:00:00
abstract：AIMS/HYPOTHESIS:Early detection of risk of microalbuminuria could prevent early renal damage. We investigated whether urine retinol binding protein and N-acetyl-glucosaminidase could predict the risk of microalbuminuria in a large cohort of children followed from diagnosis of Type I (insulin-dependent) diabetes mellitu...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s001250051603
更新日期：2001-02-01 00:00:00
abstract：:Metformin is an effective agent with a good safety profile that is widely used as a first-line treatment for type 2 diabetes, yet its mechanisms of action and variability in terms of efficacy and side effects remain poorly understood. Although the liver is recognised as a major site of metformin pharmacodynamics, rece...
journal_title：Diabetologia
pub_type： 杂志文章,评审
doi：10.1007/s00125-015-3844-9
更新日期：2016-03-01 00:00:00
abstract：AIMS/HYPOTHESIS:The WFS1 gene encodes an endoplasmic reticulum (ER) membrane-embedded protein called Wolfram syndrome 1 protein, homozygous mutations of which cause selective beta cell loss in humans. The function(s) of this protein and the mechanism by which the mutations of this gene cause beta cell death are still n...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-009-1270-6
更新日期：2009-04-01 00:00:00
abstract：:In order to establish a model for the in vivo assessment of islet function we have used the Rowett nude rat with transplantation of allogeneic and xenogeneic (mouse) islets into the renal subcapsular space following a minimal period of diabetic induction. Thirty-one nude rats were given streptozotocin and 30 became di...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF02341509
更新日期：1988-06-01 00:00:00
abstract：AIMS/HYPOTHESIS:The effect of renin inhibition on type 2 diabetes is still unclear. The present study was undertaken to examine the efficacy of aliskiren, a direct renin inhibitor, on cardiovascular injuries, glucose intolerance and pancreatic injury in a mouse model of type 2 diabetes. METHODS:Groups of db/db mice, w...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-009-1575-5
更新日期：2010-01-01 00:00:00
abstract：:The importance of both insulin resistance and beta cell dysfunction in the pathogenesis of glucose intolerance is widely recognised. Also popular is the concept that beta cell secretory function must be viewed in the context of extant insulin resistance. This For Debate moves from the premise that, whilst insulin acti...
journal_title：Diabetologia
pub_type： 杂志文章,评审
doi：10.1007/s00125-004-1381-z
更新日期：2004-05-01 00:00:00
abstract：AIMS/HYPOTHESIS:FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesit...
journal_title：Diabetologia
pub_type： 杂志文章,meta分析
doi：10.1007/s00125-011-2370-7
更新日期：2012-04-01 00:00:00
abstract：:The immune response of diabetic patients to influenza vaccination was examined in 31 patients, 10 with Type 1 (insulin-dependent) diabetes and 21 with Type 2 (non-insulin-dependent diabetes), and in 19 normal subjects. Each received a single intramuscular injection of the 3 virus strains (A/Chile,A/Philippines,B/USSR)...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00870139
更新日期：1986-12-01 00:00:00
abstract：:The basal energy expenditure of 10 Type 1 (insulin-dependent) C-peptide-negative diabetic patients (2042 +/- 62 kcal/24 h) was found to be significantly higher than the 1774 +/- 52 kcal/24 h predicted from their age, sex and body surface area (p less than 0.01). Intravenous insulin treatment significantly reduced ener...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/BF00253494
更新日期：1984-07-01 00:00:00
abstract：AIMS/HYPOTHESIS:A shift towards younger age at onset of diabetes in susceptible people has been suggested as a possible explanation for the increasing temporal trend in incidence of type 1 diabetes. We aimed to test this hypothesis by assessing trends in incidence rates in the period 1984-2004 in children and young adu...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-009-1538-x
更新日期：2009-12-01 00:00:00
abstract：AIMS/HYPOTHESIS:According to the foetal origins hypothesis, there is a relation between foetal nutrition and adult glucose intolerance. In adults, insulin resistance has been associated with dietary polyunsaturated fatty acids. We examined whether the availability of polyunsaturated fatty acids during foetal life, as i...
journal_title：Diabetologia
pub_type： 杂志文章,多中心研究
doi：10.1007/s00125-001-0764-7
更新日期：2002-03-01 00:00:00
abstract：AIMS/HYPOTHESIS:To investigate the incidence of foetal macrosomia (i.e. birth weight >90th percentile) in a non-selected nationwide cohort of women with Type I (insulin-dependent) diabetes mellitus in The Netherlands and to identify risk indicators predictive for macrosomia. METHODS:We conducted a prospective nationwi...
journal_title：Diabetologia
pub_type： 杂志文章,多中心研究
doi：10.1007/s00125-002-0958-7
更新日期：2002-11-01 00:00:00
abstract：AIMS/HYPOTHESIS:Obesity is a major risk factor for type 2 diabetes, but little is known about the contribution of BMI-associated loci to type 2 diabetes risk in East Asian populations. METHODS:In this study, 30 known BMI-associated variants and a genetic risk score (GRS) calculated by summing the BMI-increasing allele...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s00125-014-3308-7
更新日期：2014-09-01 00:00:00
abstract：:The effects of the aldose reductase inhibitor, sorbinil, on symptomatic symmetrical diabetic polyneuropathy were studied during a 6-month period in a double-blind parallel group placebo-controlled trial. Twenty-seven patients received sorbinil and 28 placebo. The patients were assessed by clinical examination, neuroph...
journal_title：Diabetologia
pub_type： 临床试验,杂志文章
doi：10.1007/BF00283137
更新日期：1985-06-01 00:00:00
abstract：AIMS/HYPOTHESIS:Patients treated with human immunodeficiency virus-1 protease inhibitors often develop impaired glucose tolerance or diabetes, most likely due to an induction of insulin resistance. We therefore investigated whether the protease inhibitor indinavir alters insulin signalling. METHODS:We incubated HepG2 ...
journal_title：Diabetologia
pub_type： 杂志文章
doi：10.1007/s001250051505
更新日期：2000-09-01 00:00:00
