Abstract:
:This article seeks to determine whether factors related to autoimmunity risk remain significant after the initiation of two or more diabetes-related autoantibodies and continue to contribute to type 1 diabetes (T1D) risk among autoantibody-positive children in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Characteristics included are age at multiple autoantibody positivity, sex, selected high-risk HLA-DR-DQ genotypes, relationship to a family member with T1D, autoantibody at seroconversion, INS gene (rs1004446_A), and non-HLA gene polymorphisms identified by the Type 1 Diabetes Genetics Consortium (T1DGC). The risk of progression to T1D was not different among those with or without a family history of T1D (P = 0.39) or HLA-DR-DQ genotypes (P = 0.74). Age at developing multiple autoantibodies (hazard ratio = 0.96 per 1-month increase in age; 95% CI 0.95, 0.97; P < 0.001) and the type of first autoantibody (when more than a single autoantibody was the first-appearing indication of seroconversion [P = 0.006]) were statistically significant. Female sex was also a significant risk factor (P = 0.03). Three single nucleotide polymorphisms were associated with increased diabetes risk (rs10517086_A [P = 0.03], rs1534422_G [P = 0.006], and rs2327832_G [P = 0.03] in TNFAIP3) and one with decreased risk (rs1004446_A in INS [P = 0.006]). The TEDDY data suggest that non-HLA gene polymorphisms may play a different role in the initiation of autoimmunity than they do in progression to T1D once autoimmunity has appeared. The strength of these associations may be related to the age of the population and the high-risk HLA-DR-DQ subtypes studied.
journal_name
Diabetesjournal_title
Diabetesauthors
Krischer JP,Liu X,Lernmark Å,Hagopian WA,Rewers MJ,She JX,Toppari J,Ziegler AG,Akolkar B,TEDDY Study Group.doi
10.2337/db17-0261subject
Has Abstractpub_date
2017-12-01 00:00:00pages
3122-3129issue
12eissn
0012-1797issn
1939-327Xpii
db17-0261journal_volume
66pub_type
杂志文章相关文献
DIABETES文献大全abstract::Antibodies to islet cell proteins detected as 37,000 and 40,000 M(r), tryptic fragments (37- and 40-kDa antigens) are strongly associated with progression to IDDM. The 40-kDa antigen has recently been identified as the tyrosine phosphatase-like protein IA-2 (ICA512) whereas the 37-kDa antigen has been suggested to be ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.45.9.1187
更新日期:1996-09-01 00:00:00
abstract::Cardiovascular diseases are the leading cause of morbidity and mortality in diabetes. Lipoprotein lipase (LPL), a major secretory product of macrophages, has been suggested to play a key role in the development of atherosclerosis. In the present study, we evaluated the effect of high glucose on macrophage LPL mRNA exp...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.47.3.431
更新日期:1998-03-01 00:00:00
abstract::A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19]) is now at global pandemic levels causing significant morbidity and mortality. Patients with diabetes are particularly vulnerable and more likely to get severe complications when infected with this vi...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/dbi20-0022
更新日期:2020-10-01 00:00:00
abstract::Treatment of male sand rats kept on a balanced laboratory chow diet ad libitum with beta,beta'-tetramethyl-substituted hexadecanedioic acid (MEDICA 16) resulted in a hypolipidemic effect accompanied by an extensive reduction in adiposity, with a concomitant hypoglycemic-hypoinsulinemic effect. The overall effect was s...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.12.1618
更新日期:1988-12-01 00:00:00
abstract::GLUT4 is necessary for acute insulin- and contraction-induced skeletal muscle glucose uptake, but its role in chronic muscle loading (overload)-induced glucose uptake is unknown. Our goal was to determine whether GLUT4 is required for overload-induced glucose uptake. Overload was induced in mouse plantaris muscle by u...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db16-1075
更新日期:2017-06-01 00:00:00
abstract:OBJECTIVE:To examine the prospective association between objectively measured time spent sedentary and insulin resistance and whether this association is independent of moderate- and vigorous-intensity physical activity (MVPA) and other relevant confounders. RESEARCH DESIGN AND METHODS:This was a population-based stud...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db08-1773
更新日期:2009-08-01 00:00:00
abstract::The data being reported are part of an epidemiologic study of health and disease in an entire community, Tecumseh, Michigan. Approximately 1,300 males age 16-65 were classified into three groups on the basis of their habitual leisure and occupational physical activity. A blood sample was drawn one hour after a glucose...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.26.3.172
更新日期:1977-03-01 00:00:00
abstract::Nondiabetic obese humans adapt to insulin resistance by increasing beta-cell mass. In contrast, obese humans with type 2 diabetes have an approximately 60% deficit in beta-cell mass. Recent studies in rodents reveal that beta-cell mass is regulated, increasing in response to insulin resistance through increased beta-c...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.52.9.2304
更新日期:2003-09-01 00:00:00
abstract::Insulin sensitivity, glucose effectiveness, and endogenous glucose production (EGP) during stable-labeled, frequently sampled insulin-modified intravenous glucose tolerance test (FSIGT) were evaluated by a single-and two-compartment minimal model combined with nonparametric deconvolution in eleven nonobese Japanese ty...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.48.5.1054
更新日期:1999-05-01 00:00:00
abstract::Diabetic nephropathy is a major complication of diabetes and a leading cause of end-stage renal diseases in the U.S. Pigment epithelium-derived factor (PEDF) is a potent angiogenic inhibitor that has been extensively studied in diabetic retinopathy. Recently, we reported that PEDF is expressed at high levels in normal...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db05-1448
更新日期:2006-06-01 00:00:00
abstract::Insulin resistance (IR) is a harbinger of type 2 diabetes (T2D) and partly determined by genetic factors. However, genetically regulated mechanisms of IR remain poorly understood. Using gene expression, genotype, and insulin sensitivity data from the African American Genetics of Metabolism and Expression (AAGMEx) coho...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db18-1229
更新日期:2019-07-01 00:00:00
abstract::Type 1 diabetes is caused by adaptive immune responses, but innate immunity is important because monocytes infiltrate islets. Activated monocytes express cyclooxygenase (COX)-2, promoting prostaglandin-E(2) (PGE(2)) secretion, whereas COX-1 expression is constitutive. We aimed to define monocyte COX expression in type...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db06-0447
更新日期:2006-12-01 00:00:00
abstract:OBJECTIVE:Pharmacogenomics is a key component of personalized medicine. The Israel Cardiovascular Events Reduction with Vitamin E Study, a prospective placebo-controlled study, recently demonstrated that vitamin E could dramatically reduce CVD in individuals with diabetes and the haptoglobin (Hp) 2-2 genotype (40% of d...
journal_title:Diabetes
pub_type: 杂志文章,随机对照试验
doi:10.2337/db08-0450
更新日期:2008-10-01 00:00:00
abstract:OBJECTIVE:Obesity causes insulin resistance, which has been interpreted as reduced downstream insulin signaling. However, changes in access of insulin to sensitive tissues such as skeletal muscle may also play a role. Insulin injected directly into skeletal muscle diffuses rapidly through the interstitial space to caus...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-0839
更新日期:2010-03-01 00:00:00
abstract::Type 2 diabetes (T2D) is hallmarked by insulin resistance, impaired insulin secretion, and increased hepatic glucose production. The worldwide increasing prevalence of T2D calls for efforts to understand its pathogenesis in order to improve disease prevention and management. Recent genome-wide association studies have...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-1921
更新日期:2014-10-01 00:00:00
abstract::Fasting hyperglycemia occurs when an excessive rate of endogenous glucose production (EGP) is not accompanied by an adequate compensatory increase in the rate of glucose disappearance (Rd). The situation following food ingestion is more complex as the amount of glucose that reaches the circulation for disposal is a fu...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db15-1166
更新日期:2016-05-01 00:00:00
abstract::To investigate the effects of insulin on platelets in obesity and in non-insulin-dependent diabetes mellitus (NIDDM)--classic insulin-resistant states--we determined ADP-induced platelet aggregation and platelet cGMP (guanosine 3',5'-cyclic monophosphate) content in platelet-rich plasma obtained from nine obese subjec...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.44.11.1318
更新日期:1995-11-01 00:00:00
abstract::Mice genetically deficient in the glucagon receptor (Gcgr(-/-)) show improved glucose tolerance, insulin sensitivity, and α-cell hyperplasia. In addition, Gcgr(-/-) mice do not develop diabetes after chemical destruction of β-cells. Since fibroblast growth factor 21 (FGF21) has insulin-independent glucose-lowering pro...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db13-0710
更新日期:2014-01-01 00:00:00
abstract::A workshop sponsored by the National Institute of Child Health and Human Development was held in June 1988 to discuss the initial events in the pathogenesis of insulin-dependent diabetes and to make recommendations for future studies. Better definition of immunological markers to reliably predict the disease will enab...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diab.38.4.534
更新日期:1989-04-01 00:00:00
abstract::Hepatocyte nuclear factor (HNF)-4alpha is a transcription factor known as a key molecule in the development and functions of the beta-cells. In a previously performed genome-wide scan of Japanese type 2 diabetic sibpairs, we observed linkage of type 2 diabetes to chromosome 20q12-q13, a region in which the HNF4A gene ...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db05-0620
更新日期:2006-05-01 00:00:00
abstract::Muscle insulin sensitivity for stimulating glucose uptake is enhanced in the period after a single bout of exercise. We recently demonstrated that AMPK is necessary for AICAR, contraction, and exercise to enhance muscle and whole-body insulin sensitivity in mice. Correlative observations from both human and rodent ske...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db18-0769
更新日期:2019-09-01 00:00:00
abstract:OBJECTIVE:Posttranslational prenylation (e.g., farnesylation) of small G-proteins is felt to be requisite for cytoskeletal remodeling and fusion of secretory vesicles with the plasma membrane. Here, we investigated roles of protein farnesylation in the signaling steps involved in Raf-1/extracellular signal-related kina...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/db09-1334
更新日期:2010-04-01 00:00:00
abstract::To determine the contribution of the rate of glucose recycling via the Cori cycle (glucose----3-carbon compounds----glucose) to the higher rate of endogenous glucose production (EGPR) in subjects with non-insulin-dependent diabetes mellitus (NIDDM), we studied eight obese, weight-stabilized diabetic Pima Indians befor...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.37.2.154
更新日期:1988-02-01 00:00:00
abstract::It has long been recognized that islet cell function is rapidly altered in vitro, but can be maintained, at least in part, when cells are layered on defined extracellular matrices. The present work addresses the influence of short-term cell-matrix interactions on islet beta-cell function and provides first insight int...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.49.2.233
更新日期:2000-02-01 00:00:00
abstract::A patient with functioning islet cell carcinoma is described who had amelioration of her hypoglycemia during the development of ectopic ACTH syndrome. Moon facies and hyperkalemic metabolic acidosis were also present in this patient, features uncommonly seen in the actopic ACTH syndrome. At autopsy, she was found to h...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.24.6.600
更新日期:1975-06-01 00:00:00
abstract::Nearly 20 years ago, it was suggested that individuals exist who are not obese on the basis of height and weight, but who, like people with overt obesity, are hyperinsulinemic, insulin-resistant, and predisposed to type 2 diabetes, hypertriglyceridemia, and premature coronary heart disease. Since then it has become in...
journal_title:Diabetes
pub_type: 杂志文章,评审
doi:10.2337/diabetes.47.5.699
更新日期:1998-05-01 00:00:00
abstract::GAD is a pancreatic beta-cell autoantigen in humans and nonobese diabetic (NOD) mice. Modulation of GAD expression in pancreatic beta-cells has been suggested to be associated with the development of autoimmune diabetes. Hormonal changes through environmental stimuli are considered to influence the expression of the d...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.51.9.2764
更新日期:2002-09-01 00:00:00
abstract::The interaction of insulin with the vascular endothelium was studied using bovine aortic endothelial cells in monolayer cultures. Confluent cell cultures exhibited specific binding of 125I-insulin to high- and low-affinity cell surface receptor sites. Binding was reversible, saturable, and accompanied by internalizati...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diacare.31.12.1077
更新日期:1982-12-01 00:00:00
abstract::The inhibitory action of insulin and proinsulin on basal and glucagon-activated glycogenolysis was studied in cultured rat hepatocytes containing [14C]glycogen. Insulin or proinsulin given as sole hormones in the presence of 5 mM glucose decreased basal release of [14C]glucose from [14C]glycogen to 20%. Half-maximal e...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diab.36.5.551
更新日期:1987-05-01 00:00:00
abstract::Liver X receptors (LXRs) are important regulators of cholesterol and lipid metabolism and are also involved in glucose metabolism. However, the functional role of LXRs in human skeletal muscle is at present unknown. This study demonstrates that chronic ligand activation of LXRs by a synthetic LXR agonist increases the...
journal_title:Diabetes
pub_type: 杂志文章
doi:10.2337/diabetes.54.4.1108
更新日期:2005-04-01 00:00:00