HLA genotyping supports a nonautoimmune etiology in patients diagnosed with diabetes under the age of 6 months.


:Children with permanent diabetes are usually assumed to have type 1 diabetes. It has recently been shown that there are genetic subgroups of diabetes that are often diagnosed during the neonatal period but may present later. A recent Italian study proposed that type 1 diabetes is rare before 6 months of age. We aimed to examine genetic susceptibility to type 1 diabetes in patients diagnosed with diabetes before the age of 2 years. We analyzed HLA class II genotypes, markers of autoimmune diabetes, in 187 children with permanent diabetes diagnosed at <2 years of age. Of the 79 subjects diagnosed at <6 months of age, 41% (95% CI 0.30-0.51) had type 1 diabetes-associated high-risk genotypes, a proportion similar to that in healthy population control subjects (44%, P=0.56). This group included 32 patients with mutations in the KCNJ11 gene, which encodes Kir6.2 (44% high-risk HLA class II genotypes), and 47 in whom the etiology of diabetes was unknown (38% high-risk HLA class II genotypes). Of 108 patients diagnosed between 6 and 24 months of age, 93% (0.86-0.99) had high-risk HLA class II genotypes compared with 44% of the population control subjects (P<0.0001). We conclude that infants diagnosed with diabetes before 6 months of age are unlikely to have autoimmune type 1 diabetes and are most likely to have a monogenic etiology.






Edghill EL,Dix RJ,Flanagan SE,Bingley PJ,Hattersley AT,Ellard S,Gillespie KM




Has Abstract


2006-06-01 00:00:00
















  • Correlation of serum triglyceride levels and hemoglobin AIc concentrations in diabetes mellitus.

    abstract::Studies in 10 nonketotic diabetic subjects (five juvenile- and five adult-onset) before and after control of carbohydrate metabolism showed a high degree of correlation between hemoglobin AIc (HbAIc) concentrations and serum triglyceride levels. Serum triglyceride levels were found to correlate more closely with Hb AI...


    pub_type: 杂志文章


    authors: Peterson CM,Koenig RJ,Jones RL,Saudek CD,Cerami A

    更新日期:1977-05-01 00:00:00

  • Inhibition of Id1 augments insulin secretion and protects against high-fat diet-induced glucose intolerance.

    abstract:OBJECTIVE:The molecular mechanisms responsible for pancreatic β-cell dysfunction in type 2 diabetes remain unresolved. Increased expression of the helix-loop-helix protein Id1 has been found in islets of diabetic mice and in vitro models of β-cell dysfunction. Here, we investigated the role of Id1 in insulin secretion ...


    pub_type: 杂志文章


    authors: Akerfeldt MC,Laybutt DR

    更新日期:2011-10-01 00:00:00

  • Insulin resistance by uncleaved insulin proreceptor. Emergence of binding site by trypsin.

    abstract::Two sisters presented with severe insulin resistance and markedly decreased insulin binding to erythrocytes, cultured fibroblasts, and transformed lymphocytes. The dose-response curve of insulin-stimulated amino acid uptake in the fibroblasts was shifted to the right. The molecular weight of the insulin receptor on th...


    pub_type: 杂志文章


    authors: Kobayashi M,Sasaoka T,Takata Y,Hisatomi A,Shigeta Y

    更新日期:1988-05-01 00:00:00

  • Mitochondrial respiration is decreased in skeletal muscle of patients with type 2 diabetes.

    abstract::We tested the hypothesis of a lower respiratory capacity per mitochondrion in skeletal muscle of type 2 diabetic patients compared with obese subjects. Muscle biopsies obtained from 10 obese type 2 diabetic and 8 obese nondiabetic male subjects were used for assessment of 3-hydroxy-Acyl-CoA-dehydrogenase (HAD) and cit...


    pub_type: 杂志文章


    authors: Mogensen M,Sahlin K,Fernström M,Glintborg D,Vind BF,Beck-Nielsen H,Højlund K

    更新日期:2007-06-01 00:00:00

  • Upregulation of mesangial growth factor and extracellular matrix synthesis by advanced glycation end products via a receptor-mediated mechanism.

    abstract::Enhanced advanced glycosylation end product (AGE) formation has been shown to participate in the pathogenesis of diabetes-induced glomerular injury by mediating the increased extracellular matrix (ECM) deposition and altered cell growth and turnover leading to mesangial expansion. These effects could be exerted via an...


    pub_type: 杂志文章


    authors: Pugliese G,Pricci F,Romeo G,Pugliese F,Mené P,Giannini S,Cresci B,Galli G,Rotella CM,Vlassara H,Di Mario U

    更新日期:1997-11-01 00:00:00

  • Studies of the peptide YY and neuropeptide Y2 receptor genes in relation to human obesity and obesity-related traits.

    abstract::Peptide-YY (PYY) is secreted from endocrine L-cells of the gastrointestinal tract in response to caloric ingestion and may mediate postprandial satiety through the hypothalamic neuropeptide Y2 receptor (Y2R). We examined whether variants in the genes encoding PYY and Y2R might be associated with obesity-related phenot...


    pub_type: 杂志文章


    authors: Hung CC,Pirie F,Luan J,Lank E,Motala A,Yeo GS,Keogh JM,Wareham NJ,O'Rahilly S,Farooqi IS

    更新日期:2004-09-01 00:00:00

  • Polymerase I and transcript release factor regulates lipolysis via a phosphorylation-dependent mechanism.

    abstract:OBJECTIVE:Polymerase I and transcript release factor (PTRF) is a protein highly expressed in adipose tissue and is an integral structural component of caveolae. Here, we report on a novel role of PTRF in lipid mobilization. RESEARCH DESIGN AND METHODS:PTRF expression was examined in different adipose depots of mice du...


    pub_type: 杂志文章


    authors: Aboulaich N,Chui PC,Asara JM,Flier JS,Maratos-Flier E

    更新日期:2011-03-01 00:00:00

  • Insulin suppresses its own secretion in vivo.

    abstract::This study addressed the controversial question of whether a negative-insulin-feedback loop exists in vivo. We utilized prehepatic insulin production, calculated by computerized deconvolution analysis of peripheral C-peptide concentration, as a measure of endogenous insulin secretion. Prehepatic insulin production was...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Argoud GM,Schade DS,Eaton RP

    更新日期:1987-08-01 00:00:00

  • Bioactives of Artemisia dracunculus L. mitigate the role of ceramides in attenuating insulin signaling in rat skeletal muscle cells.

    abstract::Ectopic lipids in peripheral tissues have been implicated in attenuating insulin action in vivo. The botanical extract of Artemisia dracunculus L. (PMI 5011) improves insulin action, yet the precise mechanism is not known. We sought to determine whether the mechanism by which PMI 5011 improves insulin signaling is thr...


    pub_type: 杂志文章


    authors: Obanda DN,Hernandez A,Ribnicky D,Yu Y,Zhang XH,Wang ZQ,Cefalu WT

    更新日期:2012-03-01 00:00:00

  • Increased frequency of apolipoprotein epsilon 4 allele in type II diabetes with hypercholesterolemia.

    abstract::The apolipoprotein E (apoE) phenotype and allele frequencies were examined in type II (non-insulin-dependent) diabetic patients with normolipidemia (n = 134) and hypercholesterolemia (type IIa hyperlipoproteinemia, n = 35; type IIb hyperlipoproteinemia, n = 42). The frequencies of apoE4-present phenotypes (apoE4/3, ap...


    pub_type: 杂志文章


    authors: Eto M,Watanabe K,Iwashima Y,Morikawa A,Chonan N,Oshima E,Sekiguchi M,Ishii K

    更新日期:1987-11-01 00:00:00

  • The effects of Goldblatt hypertension on development of the glomerular lesions of diabetes mellitus in the rat.

    abstract::Rats with classic Goldblatt (two-kidney) hypertension had diabetes induced by streptozotocin. After four months of diabetes, glomeruli of the unclipped kidney of hypertensive diabetic rats had markedly increased diabetic changes, including mesangial matrix thickening and mesangial immunoglobulin (IgG and IgM) and comp...


    pub_type: 杂志文章


    authors: Mauer SM,Steffes MW,Azar S,Sandberg SK,Brown DM

    更新日期:1978-07-01 00:00:00

  • Sequence variation in PPARG may underlie differential response to troglitazone.

    abstract::Thiazolidinediones (TZDs) are peroxisome proliferator-activated receptor-gamma (PPARG) agonists used to treat type 2 diabetes. TZDs can also be used to reduce rates of type 2 diabetes in at-risk individuals. However, a large fraction of TZD-treated patients (30-40%) do not respond to TZD treatment with an improvement ...


    pub_type: 杂志文章,随机对照试验


    authors: Wolford JK,Yeatts KA,Dhanjal SK,Black MH,Xiang AH,Buchanan TA,Watanabe RM

    更新日期:2005-11-01 00:00:00

  • Heterologous expression and characterization of rat liver glucokinase regulatory protein.

    abstract::Glucokinase is a critical component of the physiological glucose sensor found in cell types that are responsive to changes in plasma glucose levels. The acute regulation of glucokinase activity has been shown to occur via a regulatory protein found in liver parenchymal cells (Van Schaftingen E, Detheux M, Da Cunha MV....


    pub_type: 杂志文章


    authors: Mookhtiar KA,Kalinowski SS,Brown KS,Tsay YH,Smith-Monroy C,Robinson GW

    更新日期:1996-12-01 00:00:00

  • Prolactin enhances cell-to-cell communication among beta-cells in pancreatic islets.

    abstract::To determine the role of prolactin in increasing junctional communication among islet beta-cells, we studied dye coupling in pancreatic islets exposed to elevated levels of prolactin in vivo and in vitro. Islets were isolated from rats immediately after lactation or from rats bearing mammosomatotropic tumors (MtTW15),...


    pub_type: 杂志文章


    authors: Michaels RL,Sorenson RL,Parsons JA,Sheridan JD

    更新日期:1987-10-01 00:00:00

  • Lactate production in pancreatic islets.

    abstract::Lactate production, glucose utilization, glucose oxidation, and insulin release were studied in islets from rat and ob/ob mice. Lactate was determined with a highly sensitive method, based on esterification, subsequent separation, and quantitation with high-performance liquid chromatography. There was a significant la...


    pub_type: 杂志文章


    authors: Tamarit-Rodriguez J,Idahl LA,Giné E,Alcazar O,Sehlin J

    更新日期:1998-08-01 00:00:00

  • Sweet Dopamine: Sucrose Preferences Relate Differentially to Striatal D2 Receptor Binding and Age in Obesity.

    abstract::Alterations in dopaminergic circuitry play a critical role in food reward and may contribute to susceptibility to obesity. Ingestion of sweets releases dopamine in striatum, and both sweet preferences and striatal D2 receptors (D2R) decline with age and may be altered in obesity. Understanding the relationships betwee...


    pub_type: 杂志文章


    authors: Pepino MY,Eisenstein SA,Bischoff AN,Klein S,Moerlein SM,Perlmutter JS,Black KJ,Hershey T

    更新日期:2016-09-01 00:00:00

  • Fatty acid signaling in the beta-cell and insulin secretion.

    abstract::Fatty acids (FAs) and other lipid molecules are important for many cellular functions, including vesicle exocytosis. For the pancreatic beta-cell, while the presence of some FAs is essential for glucose-stimulated insulin secretion, FAs have enormous capacity to amplify glucose-stimulated insulin secretion, which is p...


    pub_type: 杂志文章,评审


    authors: Nolan CJ,Madiraju MS,Delghingaro-Augusto V,Peyot ML,Prentki M

    更新日期:2006-12-01 00:00:00

  • Mannose phosphorylation by glucokinase from liver and transplantable insulinoma. Cooperativity and discrimination of anomers.

    abstract::Glucokinase from rat liver or transplantable, radiation-induced insulinomas was partially purified by ion exchange chromatography using DEAE-Cibacron Blue F3GA agarose. Phosphorylation of alpha,beta-D-mannose by glucokinase occurred with cooperative rate dependence on mannose concentration (nH: 1.50). Half-maximal pho...


    pub_type: 杂志文章


    authors: Meglasson MD,Schinco M,Matschinsky FM

    更新日期:1983-12-01 00:00:00

  • CD5+ B lymphocytes in high-risk islet cell antibody-positive and newly diagnosed IDDM subjects.

    abstract::Human CD5+ B lymphocytes produce autoantibodies that bind to self- and exogenous antigens. Extremely high percentages of CD5+ B lymphocytes are present in the fetal and newborn periods, whereas they constitute only a minority of B lymphocytes in healthy adults. Increased percentages of circulating CD5+ lymphocytes hav...


    pub_type: 杂志文章


    authors: Schatz DA,Lang F,Cantor AB,Riley WJ,Maclaren NK,Sleasman JW,Barrett DJ

    更新日期:1991-10-01 00:00:00

  • Lower heart rate variability is associated with the development of coronary heart disease in individuals with diabetes: the atherosclerosis risk in communities (ARIC) study.

    abstract::The objective of this study was to test prospectively in a population sample whether individuals with impaired heart rate variability (HRV) are at increased risk of developing coronary heart disease (CHD) and of non-CHD mortality and to test whether this relationship is more pronounced among individuals with diabetes....


    pub_type: 杂志文章


    authors: Liao D,Carnethon M,Evans GW,Cascio WE,Heiss G

    更新日期:2002-12-01 00:00:00

  • Hyperglycemia and beta-cell adaptation during prolonged somatostatin infusion with glucagon replacement in man.

    abstract::To assess the relationship between beta-cell function and the level and duration of hyperglycemia during generalized beta-cell impairment, we studied the effects of acute and prolonged infusion of somatostatin in seven normal men. Twenty minutes after beginning an acute infusion of somatostatin (200 microgram/h) plus ...


    pub_type: 杂志文章


    authors: Ward WK,Halter JB,Best JD,Beard JC,Porte D Jr

    更新日期:1983-10-01 00:00:00

  • Women with mitochondrial haplogroup N9a are protected against metabolic syndrome.

    abstract::To identify mitochondrial haplogroups that confer resistance against or susceptibility to metabolic syndrome, we performed a large-scale association study on 1,337 unrelated Japanese individuals, including 871 subjects with metabolic syndrome and 466 control subjects. Metabolic syndrome was diagnosed according to modi...


    pub_type: 杂志文章


    authors: Tanaka M,Fuku N,Nishigaki Y,Matsuo H,Segawa T,Watanabe S,Kato K,Yokoi K,Ito M,Nozawa Y,Yamada Y

    更新日期:2007-02-01 00:00:00

  • Prevention of diabetes with pioglitazone in ACT NOW: physiologic correlates.

    abstract::We examined the metabolic characteristics that attend the development of type 2 diabetes (T2DM) in 441 impaired glucose tolerance (IGT) subjects who participated in the ACT NOW Study and had complete end-of-study metabolic measurements. Subjects were randomized to receive pioglitazone (PGZ; 45 mg/day) or placebo and w...


    pub_type: 杂志文章,随机对照试验


    authors: Defronzo RA,Tripathy D,Schwenke DC,Banerji M,Bray GA,Buchanan TA,Clement SC,Gastaldelli A,Henry RR,Kitabchi AE,Mudaliar S,Ratner RE,Stentz FB,Musi N,Reaven PD,ACT NOW Study.

    更新日期:2013-11-01 00:00:00

  • Two-color flow cytometry analysis of activated T-lymphocyte subsets in type I diabetes mellitus.

    abstract::We addressed the question of whether newly diagnosed type I (insulin-dependent) diabetes mellitus patients showed an increased number of DR (la+) T-lymphocytes compared with nondiabetic siblings and normal control subjects. Two-color flow cytometry measurements of peripheral-blood lymphocytes showed a slight but stati...


    pub_type: 杂志文章


    authors: Legendre CM,Schiffrin A,Weitzner G,Colle E,Guttmann RD

    更新日期:1988-06-01 00:00:00

  • Podocyte-Specific Loss of Krüppel-Like Factor 6 Increases Mitochondrial Injury in Diabetic Kidney Disease.

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    pub_type: 杂志文章


    authors: Horne SJ,Vasquez JM,Guo Y,Ly V,Piret SE,Leonardo AR,Ling J,Revelo MP,Bogenhagen D,Yang VW,He JC,Mallipattu SK

    更新日期:2018-11-01 00:00:00

  • Patients with chronic pancreatitis have islet progenitor cells in their ducts, but reversal of overt diabetes in NOD mice by anti-CD3 shows no evidence for islet regeneration.

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    pub_type: 杂志文章


    authors: Phillips JM,O'Reilly L,Bland C,Foulis AK,Cooke A

    更新日期:2007-03-01 00:00:00

  • Mechanism of improvement in glucose metabolism after chronic glyburide therapy.

    abstract::The effect of glyburide on glucose metabolism was examined in 10 non-insulin-dependent diabetic subjects (NIDDM) and 7 young, control subjects. After 3 mo of glyburide treatment in NIDDM, fasting plasma glucose declined from 198 to 141 mg/dl (P less than 0.01) without change in fasting insulin levels. Basal hepatic gl...


    pub_type: 杂志文章


    authors: Simonson DC,Ferrannini E,Bevilacqua S,Smith D,Barrett E,Carlson R,DeFronzo RA

    更新日期:1984-09-01 00:00:00

  • Integrated concentration of growth hormone in juvenile-onset diabetes.

    abstract::Twenty-four-hour patterns of plasma growth hormone concentrations were evaluated during 50 studies of 42 subjects with juvenile-onset diabetes mellitus. Blood was sampled continuously over 24 h using a portable peristaltic pump under conditions in which subjects remained ambulatory and maintained their daily dietary a...


    pub_type: 杂志文章


    authors: Hayford JT,Danney MM,Hendrix JA,Thompson RG

    更新日期:1980-05-01 00:00:00

  • Implications of Integrated Pancreatic Microcirculation: Crosstalk between Endocrine and Exocrine Compartments.

    abstract::The endocrine and exocrine pancreas have been studied separately by endocrinologists and gastroenterologists as two organ systems. The pancreatic islet, consisting of 1-2% mass of the whole pancreas, has long been believed to be regulated independently from the surrounding exocrine tissues. Particularly, islet blood f...


    pub_type: 杂志文章


    authors: Dybala MP,Gebien LR,Reyna ME,Yu Y,Hara M

    更新日期:2020-12-01 00:00:00

  • Lower within-subject variability of insulin detemir in comparison to NPH insulin and insulin glargine in people with type 1 diabetes.

    abstract::The aim of this randomized double-blind study was to compare the within-subject variability of the glucose-lowering effect of a novel insulin analog, insulin detemir, with that of insulin glargine and NPH insulin in people with type 1 diabetes. Fifty-four subjects (32 males and 22 females, age 38 +/- 10 years [mean +/...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Heise T,Nosek L,Rønn BB,Endahl L,Heinemann L,Kapitza C,Draeger E

    更新日期:2004-06-01 00:00:00