DNA methylation near the INS gene is associated with INS genetic variation (rs689) and type 1 diabetes in the Diabetes Autoimmunity Study in the Young.


OBJECTIVE:Mechanisms underlying the role of non-human leukocyte antigen (HLA) genetic risk variants in type 1 diabetes (T1D) are poorly understood. We aimed to test the association between methylation and non-HLA genetic risk. METHODS:We conducted a methylation quantitative trait loci (mQTL) analysis in a nested case-control study from the Dietary Autoimmunity Study in the Young. Controls (n = 83) were frequency-matched to T1D cases (n = 83) based on age, race/ethnicity, and sample availability. We evaluated 13 non-HLA genetic markers known be associated with T1D. Genome-wide methylation profiling was performed on peripheral blood samples collected prior to T1D using the Illumina 450 K (discovery set) and infinium methylation EPIC beadchip (EPIC validation) platforms. Linear regression models, adjusting for age and sex, were used to test to each single nucleotide polymorphism (SNP) -probe combination. Logistic regression models were used to test the association between T1D and methylation levels among probes with a significant mQTL. A meta-analysis was used to combine odds ratios from the two platforms. RESULTS:We identified 10 SNP-methylation probe pairs (false discovery rate (FDR) adjusted P < .05 and validation P < .05). Probes were associated with the GSDMB, C1QTNF6, IL27, and INS genes. The cg03366382 (OR: 1.9, meta-P = .0495), cg21574853 (OR: 2.5, meta-P = .0232), and cg25336198 (odds ratio: 6.6, meta-P = .0081) probes were significantly associated with T1D. The three probes were located upstream from the INS transcription start site. CONCLUSIONS:We confirmed an association between DNA methylation and rs689 that has been identified in related studies. Measurements in our study preceded the onset of T1D suggesting methylation may have a role in the relationship between INS variation and T1D development.


Pediatr Diabetes


Pediatric diabetes


Carry PM,Vanderlinden LA,Johnson RK,Dong F,Steck AK,Frohnert BI,Rewers M,Yang IV,Kechris K,Norris JM




Has Abstract


2020-06-01 00:00:00












  • Imbalance of bacteriome profiles within the Finnish Diabetes Prediction and Prevention study: Parallel use of 16S profiling and virome sequencing in stool samples from children with islet autoimmunity and matched controls.

    abstract:BACKGROUND:We set out to explore associations between the stool bacteriome profiles and early-onset islet autoimmunity, taking into account the interactions with the virus component of the microbiome. METHODS:Serial stool samples were longitudinally collected from 18 infants and toddlers with early-onset islet autoimm...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章,多中心研究


    authors: Cinek O,Kramna L,Lin J,Oikarinen S,Kolarova K,Ilonen J,Simell O,Veijola R,Autio R,Hyöty H

    更新日期:2017-11-01 00:00:00

  • Measurement site of visceral adipose tissue and prediction of metabolic syndrome in youth.

    abstract:OBJECTIVE:It is unknown whether measurement site of visceral adipose tissue (VAT) influences the relationship between VAT and associated health risk in youth and if so, whether ethnic differences exist in this relationship. We examined the influence of the measurement site of VAT on the relationships between VAT and me...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Lee S,Kuk JL,Kim Y,Arslanian SA

    更新日期:2011-05-01 00:00:00

  • Detection and treatment efficacy of hypoglycemic events in the everyday life of children younger than 7 yr.

    abstract:BACKGROUND:Mild hypoglycemia is commonly observed in children treated for type 1 diabetes mellitus (T1DM). Hypoglycemia disturbs cognition and learning. OBJECTIVE:To describe how and to what extent hypoglycemia in young children with T1DM is detected in everyday life. To learn how parents and caregivers treat hypoglyc...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Sundberg F,Forsander G

    更新日期:2014-02-01 00:00:00

  • Longitudinal assessment of hippocampus structure in children with type 1 diabetes.

    abstract::The extant literature finds that children with type 1 diabetes mellitus (T1D) experience mild cognitive alterations compared to healthy age-matched controls. The neural basis of these cognitive differences is unclear but may relate in part to the effects of dysglycemia on the developing brain. We investigated longitud...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Foland-Ross LC,Reiss AL,Mazaika PK,Mauras N,Weinzimer SA,Aye T,Tansey MJ,White NH,Diabetes Research in Children Network (DirecNet).

    更新日期:2018-04-19 00:00:00

  • The changing presentation of children with newly diagnosed type 1 diabetes mellitus.

    abstract::Although it is known that the incidence of type 1 diabetes mellitus (DM) in childhood is progressively increasing, it is less clear whether the presentation of newly diagnosed DM is changing. The aim of this study was to establish whether any biochemical or clinical presentation parameters have altered over time. A re...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Jackson W,Hofman PL,Robinson EM,Elliot RB,Pilcher CC,Cutfield WS

    更新日期:2001-12-01 00:00:00

  • Prediction and prevention of type 1 diabetes: update on success of prediction and struggles at prevention.

    abstract::Type 1 diabetes mellitus (T1DM) is the archetypal example of a T cell-mediated autoimmune disease characterized by selective destruction of pancreatic β cells. The pathogenic equation for T1DM presents a complex interrelation of genetic and environmental factors, most of which have yet to be identified. On the basis o...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章,评审


    authors: Michels A,Zhang L,Khadra A,Kushner JA,Redondo MJ,Pietropaolo M

    更新日期:2015-11-01 00:00:00

  • Twenty-one years of prospective incidence of childhood type 1 diabetes in Hungary--the rising trend continues (or peaks and highlands?).

    abstract::The aim of this study was to examine secular trends in the incidence of type 1 diabetes in children aged 0-14 yr in Hungary over the period 1989-2009. Newly diagnosed children with type 1 diabetes aged 0-14 yr in Hungary were prospectively registered from 1989 to 2009. Primary ascertainment of cases was by prospective...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Gyurus EK,Patterson C,Soltesz G,Hungarian Childhood Diabetes Epidemiology Group.

    更新日期:2012-02-01 00:00:00

  • Insulin Resistance during normal child growth and development is associated with a distinct blood metabolic phenotype (Earlybird 72).

    abstract:BACKGROUND:While insulin resistance (IR) is associated with specific metabolite signatures in adults, there have been few truly longitudinal studies in healthy children, either to confirm which abnormalities are present, or to determine whether they precede or result from IR. Therefore, we investigated the association ...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Hosking J,Pinkney J,Jeffery A,Cominetti O,Da Silva L,Collino S,Kussmann M,Hager J,Martin FP

    更新日期:2019-11-01 00:00:00

  • Triple diabetes: coexistence of type 1 diabetes mellitus and a novel mutation in the gene responsible for MODY3 in an overweight adolescent.

    abstract::We report an interesting and unique case of an overweight adolescent with a novel mutation of the maturity-onset diabetes of the young (MODY)3 gene [hepatocyte nuclear factor-1 alpha (HNF-1alpha)] and positive islet cell autoantibodies. The patient is a 17-yr-old Caucasian female, who was diagnosed with type 2 diabete...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Bowden SA,Hoffman RP

    更新日期:2008-04-01 00:00:00

  • The ENCOURAGE healthy families study: A comparative effectiveness trial to reduce risk for type 2 diabetes in mothers and children.

    abstract:INTRODUCTION:Trials in adults have demonstrated that interventions targeting lifestyle are effective in preventing or delaying type 2 diabetes (T2D). To address this need in youth, we developed ENCOURAGE Healthy Families (ENCOURAGE), based on the US Diabetes Prevention Program (DPP). STUDY DESIGN:Here, we present resu...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Hannon TS,Saha CK,Carroll AE,Palmer KN,O'Kelly Phillips E,Marrero DG

    更新日期:2018-05-20 00:00:00

  • A multivariate model exploring the predictive value of demographic, adolescent, and family factors on glycemic control in adolescents with type 1 diabetes.

    abstract:OBJECTIVE:The current study examined how a comprehensive set of variables from multiple domains, including at the adolescent and family level, were predictive of glycemic control in adolescents with type 1 diabetes (T1D). METHODS:Participants included 100 adolescents with T1D ages 10-16 yrs and their parents. Particip...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Agarwal S,Jawad AF,Miller VA

    更新日期:2016-11-01 00:00:00

  • Use of a real-time continuous glucose monitoring system in children and young adults on insulin pump therapy: patients' and caregivers' perception of benefit.

    abstract:BACKGROUND:Real-time continuous glucose monitoring systems (RT-CGMS) are a recently introduced technology for type 1 diabetes and experience in children is limited. OBJECTIVE:To assess patient and caregiver's perception of benefits and disadvantages of RT-CGMS in children or young adults with type 1 diabetes mellitus ...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Cemeroglu AP,Stone R,Kleis L,Racine MS,Postellon DC,Wood MA

    更新日期:2010-05-01 00:00:00

  • Intramyocellular lipid, adiposity, and muscle oxygen supply in prepubertal type 1 diabetes.

    abstract:BACKGROUND:In the non-diabetic population, intramyocellular lipid (IMCL) accumulation is associated with obesity and poor muscle oxygen supply. IMCL levels are increased in type 1 diabetes, but their significance is less clear. METHODS:We studied a group of 16 prepubertal boys (age 6.4-9.9 yr) with type 1 diabetes and...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Ling AH,Donaghue KC,Howard NJ,Arrowsmith FE,Ward JA,Baur LA,Thompson CH

    更新日期:2003-09-01 00:00:00

  • Permanent neonatal diabetes with arthrogryposis multiplex congenita and neurogenic bladder - a new syndrome?

    abstract::Neonatal diabetes mellitus is a rare (1/400 000 newborns) but potentially devastating condition, which may be transient or permanent; typical symptoms occur within the first 4 wk of life. The transient form is a developmental insulin production disorder that resolves postnatally. Fifty to 60% of cases can be seen as t...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Goksen D,Darcan S,Coker M,Aksu G,Yildiz B,Kara S,Kültürsay N

    更新日期:2006-10-01 00:00:00

  • Inflammatory cytokine, growth factor and counterregulatory responses to exercise in children with type 1 diabetes and healthy controls.

    abstract::In children with type 1 diabetes (T1DM), altered adaptive responses to exercise (secretion of growth factors, inflammatory cytokines, and glucoregulatory mediators) may have potential implications in growth and development, early onset of disease complications, and incidence of hypoglycemia. We therefore measured a br...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Galassetti PR,Iwanaga K,Crisostomo M,Zaldivar FP,Larson J,Pescatello A

    更新日期:2006-02-01 00:00:00

  • Islet/pancreas transplantation: challenges for pediatrics.

    abstract::Beta cell replacement is a valid alternative to exogenous insulin injections to treat type 1 diabetic patients. The rate of success obtained after whole-pancreas transplantation, performed alone or in combination with kidney, and, as shown recently, by islet transplantation, justifies optimism and sets the stage for a...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Bottino R,Balamurugan AN,Giannoukakis N,Trucco M

    更新日期:2002-12-01 00:00:00

  • Treatment adherence and BMI reduction are key predictors of HbA1c 1 year after diagnosis of childhood type 2 diabetes in the United Kingdom.

    abstract:BACKGROUND/OBJECTIVE:Type 2 Diabetes (T2DM) is increasing in childhood especially among females and South-Asians. Our objective was to report outcomes from a national cohort of children and adolescents with T2DM 1 year following diagnosis. METHODS:Clinician reported, 1-year follow-up of a cohort of children (<17 years...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Candler TP,Mahmoud O,Lynn RM,Majbar AA,Barrett TG,Shield JPH

    更新日期:2018-12-01 00:00:00

  • Incidence of type 1 diabetes mellitus in 0 to 14-yr-old children in Croatia--2004 to 2012 study.

    abstract:BACKGROUND:The incidence of type 1 diabetes mellitus (T1DM) among children and adolescents increased during the last 50 yr. The T1DM incidence in Croatia was 8.87/100.000/yr over 1995-2003, with an annual increase of 9%, which placed Croatia among countries with moderate risk for T1DM. AIM:To investigate incidence rat...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Rojnic Putarek N,Ille J,Spehar Uroic A,Skrabic V,Stipancic G,Krnic N,Radica A,Marjanac I,Severinski S,Svigir A,Bogdanic A,Dumic M

    更新日期:2015-09-01 00:00:00

  • Validation of a self-report version of the diabetes self-management profile.

    abstract::Inadequate treatment adherence impedes achievement of glycemic control targets in type 1 diabetes (T1D). Valid and reliable measurement of treatment adherence is a prerequisite to rigorous evaluation of pertinent interventions. The diabetes self-management profile (DSMP), a structured interview measure of T1D adherenc...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Wysocki T,Buckloh LM,Antal H,Lochrie A,Taylor A

    更新日期:2012-08-01 00:00:00

  • Aerobic exercise capacity in normal adolescents and those with type 1 diabetes mellitus.

    abstract:OBJECTIVE:To compare the aerobic exercise capacity between normal adolescents and those with type 1 diabetes mellitus (T1DM). METHODS:An experimental group with 72 individuals diagnosed with T1DM aged 9--20, time from diagnosis 4.9 +/- 3.6 yr, without clinical cardiopulmonary disease or anemia and a control group (C) ...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Komatsu WR,Gabbay MA,Castro ML,Saraiva GL,Chacra AR,de Barros Neto TL,Dib SA

    更新日期:2005-09-01 00:00:00

  • Insulin pump use in young children in the T1D Exchange clinic registry is associated with lower hemoglobin A1c levels than injection therapy.

    abstract::Insulin delivery via injection and continuous subcutaneous insulin infusion (CSII) via insulin pump were compared in a cross-sectional study (n = 669) and retrospective longitudinal study (n = 1904) of young children (<6 yr) with type 1 diabetes (T1D) participating in the T1D Exchange clinic registry. Use of CSII corr...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Blackman SM,Raghinaru D,Adi S,Simmons JH,Ebner-Lyon L,Chase HP,Tamborlane WV,Schatz DA,Block JM,Litton JC,Raman V,Foster NC,Kollman CR,DuBose SN,Miller KM,Beck RW,DiMeglio LA

    更新日期:2014-12-01 00:00:00

  • Glucose metabolism in children and adolescents: Population-based reference values and comparisons to children and adolescents enrolled in obesity treatment.

    abstract:BACKGROUND:Alterations in glucose metabolism that lead to the development of metabolic and cardiovascular disease may begin already in childhood. OBJECTIVE:This study aims to generate pediatric age and sex-specific reference values for fasting concentrations of glucose, hemoglobin A1c (HbA1c), insulin, C-peptide, and ...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Frithioff-Bøjsøe C,Lund MAV,Kloppenborg JT,Nielsen TTH,Fonvig CE,Lausten-Thomsen U,Hedley PL,Hansen T,Pedersen OB,Christiansen M,Baker JL,Hansen T,Holm JC

    更新日期:2019-08-01 00:00:00

  • Gender differences in the relationship between parental report of self-regulation skills and adolescents' management of type 1 diabetes.

    abstract:OBJECTIVE:To examine the extent to which self-regulation skills of adolescents with type 1 diabetes (T1D), including executive functioning and emotion regulation, relate to treatment adherence and glycemic control. METHOD:Participants were 109 adolescents aged 12-18 yr with TID and their primary caregiver who attended...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Graziano PA,Geffken GR,Williams LB,Lewin AB,Duke DC,Storch EA,Silverstein JH

    更新日期:2011-06-01 00:00:00

  • A 10-yr follow-up study for the detection of peripheral neuropathy in young patients with type 1 diabetes.

    abstract:OBJECTIVE:The main objective of this work was to follow-up the development of diabetic neuropathy (DN) and its severity in patients with type 1 diabetes over 10 yr. Our intention was also to observe risk factor changes and verify which of them influence the development of neuropathy. The other objective was longitudina...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Hajas G,Kissova V,Tirpakova A

    更新日期:2016-12-01 00:00:00

  • The influence of physical activity on ghrelin and IGF-1/IGFBP-3 levels in children and adolescents with type 1 diabetes mellitus.

    abstract:OBJECTIVES:The aim of the study was to determine the influence of regular physical activity on ghrelin and IGF-1/IGFBP-3 levels during a diabetes camp. METHODS:Twenty-eight children and adolescents (14 boys; mean age 12.1 yr) with type 1 diabetes mellitus (T1DM, mean duration of diabetes 4.8 yr) attending a 2-wk diabe...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Huber J,Fröhlich-Reiterer EE,Sudi K,Suppan E,Weinhandl G,Jasser-Nitsche H,Aigner R,Borkenstein MH

    更新日期:2010-09-01 00:00:00

  • Long-term metabolic consequences of being born small for gestational age.

    abstract::This review highlights the evidence of linking small for gestational age (SGA) with metabolic/cardiovascular disturbances (dysmetabolic syndrome) in later life. The metabolic and cardiovascular complications associated with in utero undernutrition have been identified during the past 10 yr. Reduced fetal growth is ind...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章,评审


    authors: Levy-Marchal C,Jaquet D

    更新日期:2004-09-01 00:00:00

  • Partial remission in Brazilian children and adolescents with type 1 diabetes. Association with a haplotype of class II human leukocyte antigen and synthesis of autoantibodies.

    abstract:OBJECTIVE:Characterization of partial remission using the insulin dose-adjusted HbA1c (IDAA1c) ≤ 9 definition in a multiethnic Brazilian population of children and adolescents with type 1 diabetes (T1D), in addition with the determination of both Class II HLA genotype and autoantibodies. METHODS:We analyzed the preval...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Camilo DS,Pradella F,Paulino MF,Baracat ECE,Marini SH,Guerra G Jr,Pavin EJ,Parisi C,Longhini ALF,Marques SB,Guariento EG,Lieber SR,Macedo CF,Gama E Silva L,Farias AS,Santos LMB,Volpini WMG

    更新日期:2020-06-01 00:00:00

  • Changes in body composition after a 12-wk aerobic exercise program in obese boys.

    abstract:UNLABELLED:Previous studies have shown that vigorous aerobic training programs for obese children result in minimal weight changes, and concluded that they may not be beneficial. Weight change alone may not detect important beneficial changes in body composition associated with vigorous training in these children. Fift...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: DeStefano RA,Caprio S,Fahey JT,Tamborlane WV,Goldberg B

    更新日期:2000-06-01 00:00:00

  • Clinical application of regulatory T cells in type 1 diabetes.

    abstract::Regulatory T cells (Tregs) are responsible for the maintenance of peripheral tolerance. Animal studies have shown that administration of Tregs can prevent type 1 diabetes (DM1). Several clinical trials attempted to induce Tregs with various agents, and thus provide long-term tolerance of β cells in DM1. Nevertheless, ...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章,评审


    authors: Marek-Trzonkowska N,Myśliwec M,Siebert J,Trzonkowski P

    更新日期:2013-08-01 00:00:00

  • Blood pressure measurement methodology and technology in the SWEET diabetes centers: An international SWEET database survey.

    abstract:INTRODUCTION:The accuracy of blood pressure (BP) measurement is a prerequisite for the reliable diagnosis and management of hypertension. OBJECTIVES:This survey evaluated the use of office and out-of-office BP measurements and the antihypertensive pharmacological treatment in expert pediatric diabetes centers. METHOD...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Gerasimidi-Vazeou A,Birkebaek NH,Iotova V,Cherubini V,Piccini B,Biester T,Stipancic G,Jefferies C,Maffeis C,Stergiou GS,SWEET study group.

    更新日期:2020-12-01 00:00:00