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
















  • Effect of two amino acids in TM17 of Sulfonylurea receptor SUR1 on the binding of ATP-sensitive K+ channel modulators.

    abstract::The sulfonylurea receptor (SUR) is the important regulatory subunit of ATP-sensitive K+ channels. It is an ATP-binding cassette protein comprising 17 transmembrane helices. SUR is endowed with binding sites for channel blockers like the antidiabetic sulfonylurea glibenclamide and for the chemically very heterogeneous ...


    pub_type: 杂志文章


    authors: Hambrock A,Kayar T,Stumpp D,Osswald H

    更新日期:2004-12-01 00:00:00

  • Influence of hyperinsulinemia and insulin resistance on in vivo β-cell function: their role in human β-cell dysfunction.

    abstract:OBJECTIVE:Recent work has shown that insulin stimulates its own secretion in insulin-sensitive humans, suggesting that insulin resistance in the β-cell could cause β-cell dysfunction. We have tested whether insulin exposure and insulin sensitivity modulate β-cell function in subjects with normal glucose tolerance (NGT)...


    pub_type: 临床试验,杂志文章


    authors: Mari A,Tura A,Natali A,Anderwald C,Balkau B,Lalic N,Walker M,Ferrannini E,RISC Investigators.

    更新日期:2011-12-01 00:00:00

  • Endogenous glucose production and glucose effectiveness in type 2 diabetic subjects derived from stable-labeled minimal model approach.

    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...


    pub_type: 杂志文章


    authors: Nagasaka S,Tokuyama K,Kusaka I,Hayashi H,Rokkaku K,Nakamura T,Kawakami A,Higashiyama M,Ishikawa S,Saito T

    更新日期:1999-05-01 00:00:00

  • Assessment of the severity of hypoglycemia and glycemic lability in type 1 diabetic subjects undergoing islet transplantation.

    abstract::Currently, the major indications for solitary islet transplantation are recurrent severe hypoglycemia and labile glucose control. Quantifying these problems remains subjective. We have developed a scoring system for both hypoglycemia and glycemic lability, established normative data, and used them in patients who have...


    pub_type: 杂志文章,多中心研究


    authors: Ryan EA,Shandro T,Green K,Paty BW,Senior PA,Bigam D,Shapiro AM,Vantyghem MC

    更新日期:2004-04-01 00:00:00

  • Factors in development of diabetic neuropathy. Baseline analysis of neuropathy in feasibility phase of Diabetes Control and Complications Trial (DCCT). The DCCT Research Group.

    abstract::The Diabetes Control and Complications Trial (DCCT) is a multicenter randomized clinical trial studying the effect of intensive insulin therapy on the early vascular and neurological complications of insulin-dependent diabetes mellitus (IDDM). During the feasibility phase of the DCCT, baseline neurological histories, ...


    pub_type: 临床试验,杂志文章,随机对照试验



    更新日期:1988-04-01 00:00:00

  • Beta-cell adaptation and decompensation during the progression of diabetes.

    abstract::Inadequate beta-cell function is an essential component of all forms of diabetes. The most obvious problem is a failure to maintain sufficient beta-cell mass and function to cope with whatever insulin resistance is present. The most striking functional defect is a loss of acute glucose-induced insulin secretion (GIIS)...


    pub_type: 杂志文章,评审


    authors: Weir GC,Laybutt DR,Kaneto H,Bonner-Weir S,Sharma A

    更新日期:2001-02-01 00:00:00

  • Time-Resolved Autoantibody Profiling Facilitates Stratification of Preclinical Type 1 Diabetes in Children.

    abstract::Progression to clinical type 1 diabetes varies among children who develop β-cell autoantibodies. Differences in autoantibody patterns could relate to disease progression and etiology. Here we modeled complex longitudinal autoantibody profiles by using a novel wavelet-based algorithm. We identified clusters of similar ...


    pub_type: 杂志文章


    authors: Endesfelder D,Zu Castell W,Bonifacio E,Rewers M,Hagopian WA,She JX,Lernmark Å,Toppari J,Vehik K,Williams AJK,Yu L,Akolkar B,Krischer JP,Ziegler AG,Achenbach P,TEDDY Study Group.

    更新日期:2019-01-01 00:00:00

  • Hepatic and extrahepatic responses to insulin in NIDDM and nondiabetic humans. Assessment in absence of artifact introduced by tritiated nonglucose contaminants.

    abstract::It is well established that patients with non-insulin-dependent diabetes mellitus (NIDDM) are resistant to insulin. However, the contribution of hepatic and extrahepatic tissues to insulin resistance remains controversial. The uncertainty may be at least in part due to errors introduced by the unknowing use in previou...


    pub_type: 临床试验,杂志文章


    authors: Butler PC,Kryshak EJ,Schwenk WF,Haymond MW,Rizza RA

    更新日期:1990-02-01 00:00:00

  • Fetal programming of perivenous glucose uptake reveals a regulatory mechanism governing hepatic glucose output during refeeding.

    abstract::Increased hepatic gluconeogenesis maintains glycemia during fasting and has been considered responsible for elevated hepatic glucose output in type 2 diabetes. Glucose derived periportally via gluconeogenesis is partially taken up perivenously in perfused liver but not in adult rats whose mothers were protein-restrict...


    pub_type: 杂志文章


    authors: Murphy HC,Regan G,Bogdarina IG,Clark AJ,Iles RA,Cohen RD,Hitman GA,Berry CL,Coade Z,Petry CJ,Burns SP

    更新日期:2003-06-01 00:00:00

  • Effects of salsalate therapy on recovery from vascular injury in female Zucker fatty rats.

    abstract:OBJECTIVE:Salsalate is a dimeric form of salicylic acid that has been shown to have anti-inflammatory activity and to reduce glucose levels, insulin resistance, and cytokine expression. However, the effect of salsalate on vascular injury has not been determined. The objective of this study is to investigate the effect ...


    pub_type: 杂志文章


    authors: Murthy SN,Desouza CV,Bost NW,Hilaire RC,Casey DB,Badejo AM,Dhaliwal JS,McGee J,McNamara DB,Kadowitz PJ,Fonseca VA

    更新日期:2010-12-01 00:00:00

  • Pharmacological vasodilation improves insulin-stimulated muscle protein anabolism but not glucose utilization in older adults.

    abstract:OBJECTIVE:Skeletal muscle protein metabolism is resistant to the anabolic action of insulin in healthy, nondiabetic older adults. This defect is associated with impaired insulin-induced vasodilation and mTORC1 signaling. We hypothesized that, in older subjects, pharmacological restoration of insulin-induced capillary r...


    pub_type: 杂志文章


    authors: Timmerman KL,Lee JL,Fujita S,Dhanani S,Dreyer HC,Fry CS,Drummond MJ,Sheffield-Moore M,Rasmussen BB,Volpi E

    更新日期:2010-11-01 00:00:00

  • Banting Lecture: glucose turnover. A key to understanding the pathogenesis of diabetes (indirect effects of insulin).

    abstract::This article is divided into two parts. A retrospective overview summarizes some of the work that provided the framework and tools of the more recent studies. The five novel areas of research are related to the indirect effects of insulin. Regulation of plasma glucose is of central importance in health and diabetes. U...


    pub_type: 杂志文章,评审


    authors: Vranic M

    更新日期:1992-09-01 00:00:00

  • The network of glucokinase-expressing cells in glucose homeostasis and the potential of glucokinase activators for diabetes therapy.

    abstract::The glucose-phosphorylating enzyme glucokinase has structural, kinetic, and molecular genetic features that are ideal for its primary role as glucose sensor in a network of neuro/endocrine sentinel cells that maintain glucose homeostasis in many vertebrates including humans. The glucokinase-containing, insulin-produci...


    pub_type: 杂志文章,评审


    authors: Matschinsky FM,Magnuson MA,Zelent D,Jetton TL,Doliba N,Han Y,Taub R,Grimsby J

    更新日期:2006-01-01 00:00:00

  • Quantitative and qualitative lipoprotein abnormalities in diabetes mellitus.

    abstract::In people with diabetes, the concentration of an individual lipoprotein or apolipoprotein can be highly variable and is totally different in the two major forms of the disease. Alterations in the concentrations of major lipids and lipoproteins are well characterized in both IDDM and NIDDM. In general, the lipoprotein ...


    pub_type: 杂志文章,评审


    authors: Taskinen MR

    更新日期:1992-10-01 00:00:00

  • Ghrelin, an endogenous growth hormone secretagogue, is a novel orexigenic peptide that antagonizes leptin action through the activation of hypothalamic neuropeptide Y/Y1 receptor pathway.

    abstract::Ghrelin, an endogenous ligand for growth hormone secretagogue (GHS) receptor originally isolated from the stomach, occurs in the hypothalamic arcuate nucleus and may play a role in energy homeostasis. Synthetic GHSs have activated the hypothalamic arcuate neurons containing neuropeptide Y (NPY), suggesting the involve...


    pub_type: 杂志文章


    authors: Shintani M,Ogawa Y,Ebihara K,Aizawa-Abe M,Miyanaga F,Takaya K,Hayashi T,Inoue G,Hosoda K,Kojima M,Kangawa K,Nakao K

    更新日期:2001-02-01 00:00:00

  • In vivo chloroquine-induced inhibition of insulin degradation in a diabetic patient with severe insulin resistance.

    abstract::We report on a 26-yr-old patient with an 11-yr history of insulin-dependent diabetes mellitus who exhibited insulin resistance with a requirement of up to 15,000 U of intravenous (i.v.) insulin/day. Attempts to diminish her insulin requirement by administration of sulfated insulin or Trasylol were unsuccessful, with t...


    pub_type: 杂志文章


    authors: Blazar BR,Whitley CB,Kitabchi AE,Tsai MY,Santiago J,White N,Stentz FB,Brown DM

    更新日期:1984-12-01 00:00:00

  • Effects of skyrin, a receptor-selective glucagon antagonist, in rat and human hepatocytes.

    abstract::Peptidic glucagon antagonists have been shown to lower blood glucose levels in diabetic models (1-3), but attempts to identify small molecular weight glucagon receptor-binding antagonists have met with little success. Skyrin, a fungal bisanthroquinone, exhibits functional glucagon antagonism by uncoupling the glucagon...


    pub_type: 杂志文章


    authors: Parker JC,McPherson RK,Andrews KM,Levy CB,Dubins JS,Chin JE,Perry PV,Hulin B,Perry DA,Inagaki T,Dekker KA,Tachikawa K,Sugie Y,Treadway JL

    更新日期:2000-12-01 00:00:00

  • Lack of glucagon response to hypoglycemia in type I diabetics after long-term optimal therapy with a continuous subcutaneous insulin infusion pump.

    abstract::Counterregulatory hormonal responses were studied in six patients after 4-18 mo treatment with a continuous subcutaneous insulin infusion pump. In response to insulin-induced hypoglycemia, significant increases in epinephrine, norepinephrine, cortisol, and growth hormone were measured in all subjects, while in five of...


    pub_type: 杂志文章


    authors: Bergenstal RM,Polonsky KS,Pons G,Jaspan JB,Rubenstein AH

    更新日期:1983-05-01 00:00:00

  • Noninvasive detection of cardiac sympathetic nervous dysfunction in diabetic patients using [123I]metaiodobenzylguanidine.

    abstract::The association between clinical autonomic dysfunction and myocardial MIBG accumulation was investigated. The study groups comprised 6 male diabetic patients with autonomic neuropathy (ANP+ group), 6 male diabetic patients without autonomic neuropathy (ANP-group), and 6 male nondiabetic control subjects. The mean age ...


    pub_type: 杂志文章


    authors: Mäntysaari M,Kuikka J,Mustonen J,Tahvanainen K,Vanninen E,Länsimies E,Uusitupa M

    更新日期:1992-09-01 00:00:00

  • Accumulation of 8-hydroxy-2'-deoxyguanosine and mitochondrial DNA deletion in kidney of diabetic rats.

    abstract::Oxidative stress may contribute to the pathogenesis of diabetic nephropathy. However, the detailed molecular mechanism remains uncertain. Here, we report oxidative mitochondrial DNA (mtDNA) damage and accumulation of mtDNA with a 4,834-bp deletion in kidney of streptozotocin-induced diabetic rats. At 8 weeks after the...


    pub_type: 杂志文章


    authors: Kakimoto M,Inoguchi T,Sonta T,Yu HY,Imamura M,Etoh T,Hashimoto T,Nawata H

    更新日期:2002-05-01 00:00:00

  • Growth hormone overexpression in the central nervous system results in hyperphagia-induced obesity associated with insulin resistance and dyslipidemia.

    abstract::It is well known that peripherally administered growth hormone (GH) results in decreased body fat mass. However, GH-deficient patients increase their food intake when substituted with GH, suggesting that GH also has an appetite stimulating effect. Transgenic mice with an overexpression of bovine GH in the central nerv...


    pub_type: 杂志文章


    authors: Bohlooly-Y M,Olsson B,Bruder CE,Lindén D,Sjögren K,Bjursell M,Egecioglu E,Svensson L,Brodin P,Waterton JC,Isaksson OG,Sundler F,Ahrén B,Ohlsson C,Oscarsson J,Törnell J

    更新日期:2005-01-01 00:00:00

  • U.K. prospective diabetes study 16. Overview of 6 years' therapy of type II diabetes: a progressive disease. U.K. Prospective Diabetes Study Group.

    abstract::The objective of the U.K. Prospective Diabetes Study is to determine whether improved blood glucose control in type II diabetes will prevent the complications of diabetes and whether any specific therapy is advantageous or disadvantageous. The study will report in 1998, when the median duration from randomization will...


    pub_type: 临床试验,杂志文章,多中心研究,随机对照试验



    更新日期:1995-11-01 00:00:00

  • Disruption of hepatic leptin signaling protects mice from age- and diet-related glucose intolerance.

    abstract:OBJECTIVE:The liver plays a critical role in integrating and controlling glucose metabolism. Thus, it is important that the liver receive and react to signals from other tissues regarding the nutrient status of the body. Leptin, which is produced and secreted from adipose tissue, is a hormone that relays information re...


    pub_type: 杂志文章


    authors: Huynh FK,Levi J,Denroche HC,Gray SL,Voshol PJ,Neumann UH,Speck M,Chua SC,Covey SD,Kieffer TJ

    更新日期:2010-12-01 00:00:00

  • Production of 12-hydroxyeicosatetraenoic acid and vitamin E status in platelets from type I human diabetic subjects.

    abstract::Vitamin E content and biosynthesis of 12-hydroxyeicosatetraenoic acid (12-HETE) have been measured in platelets from type I diabetic subjects and age- and sex-matched, nondiabetic control subjects. Platelets from diabetic subjects synthesized significantly greater quantities of 12-HETE than did platelets from control ...


    pub_type: 杂志文章


    authors: Karpen CW,Cataland S,O'Dorisio TM,Panganamala RV

    更新日期:1985-06-01 00:00:00

  • Cellular Origins of Beige Fat Cells Revisited.

    abstract::Activated beige adipocytes have therapeutic potential due to their ability to improve glucose and lipid homeostasis. To date, the origin of beige adipocytes remains enigmatic. Whether beige cells arise through de novo differentiation from resident precursors or through reprogramming of mature white adipocytes has been...


    pub_type: 杂志文章


    authors: Shao M,Wang QA,Song A,Vishvanath L,Busbuso NC,Scherer PE,Gupta RK

    更新日期:2019-10-01 00:00:00

  • Decreased cardiac glutathione peroxidase levels and enhanced mandibular apoptosis in malformed embryos of diabetic rats.

    abstract:OBJECTIVE:To characterize normal and malformed embryos within the same litters from control and diabetic rats for expression of genes related to metabolism of reactive oxygen species (ROS) or glucose as well as developmental genes. RESEARCH DESIGN AND METHODS:Embryos from nondiabetic and streptozotocin-induced diabeti...


    pub_type: 杂志文章


    authors: Wentzel P,Gäreskog M,Eriksson UJ

    更新日期:2008-12-01 00:00:00

  • Mitochondrial respiratory capacity and content are normal in young insulin-resistant obese humans.

    abstract::Considerable debate exists about whether alterations in mitochondrial respiratory capacity and/or content play a causal role in the development of insulin resistance during obesity. The current study was undertaken to determine whether such alterations are present during the initial stages of insulin resistance in hum...


    pub_type: 杂志文章


    authors: Fisher-Wellman KH,Weber TM,Cathey BL,Brophy PM,Gilliam LA,Kane CL,Maples JM,Gavin TP,Houmard JA,Neufer PD

    更新日期:2014-01-01 00:00:00

  • Insulin and metformin regulate circulating and adipose tissue chemerin.

    abstract:OBJECTIVE:To assess chemerin levels and regulation in sera and adipose tissue from women with polycystic ovary syndrome (PCOS) and matched control subjects. RESEARCH DESIGN AND METHODS:Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of chemerin. Serum chemerin was measured by enzy...


    pub_type: 杂志文章


    authors: Tan BK,Chen J,Farhatullah S,Adya R,Kaur J,Heutling D,Lewandowski KC,O'Hare JP,Lehnert H,Randeva HS

    更新日期:2009-09-01 00:00:00

  • A genome-wide scan for type 2 diabetes in African-American families reveals evidence for a locus on chromosome 6q.

    abstract::African Americans are at increased risk of type 2 diabetes and many diabetes complications. We have carried out a genome-wide scan for African American type 2 diabetes using 638 affected sibling pairs (ASPs) from 247 families ascertained through impaired renal function to identify type 2 diabetes loci in this high-ris...


    pub_type: 杂志文章


    authors: Sale MM,Freedman BI,Langefeld CD,Williams AH,Hicks PJ,Colicigno CJ,Beck SR,Brown WM,Rich SS,Bowden DW

    更新日期:2004-03-01 00:00:00

  • Intrahepatic glucose flux as a mechanism for defective intrahepatic islet alpha-cell response to hypoglycemia.

    abstract:OBJECTIVE:Glucagon responses to hypoglycemia from islets transplanted in the liver are defective. To determine whether this defect is related to intrahepatic glycogen, islets from inbred Lewis rats were transplanted into the hepatic sinus (H group), peritoneal cavity (P group), omentum (O group), and kidney capsule (K ...


    pub_type: 杂志文章


    authors: Zhou H,Zhang T,Bogdani M,Oseid E,Parazzoli S,Vantyghem MC,Harmon J,Slucca M,Robertson RP

    更新日期:2008-06-01 00:00:00