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












  • The IDF Life for a Child Program Index of diabetes care for children and youth.

    abstract:BACKGROUND AND OBJECTIVES:Care for children and youth with diabetes varies markedly around the world. We developed a standardized, reproducible measure that can be used to document and compare critical factors influencing treatment outcomes. METHODS:A questionnaire consisting of 36 multiple-choice questions covering m...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Ogle GD,Middlehurst AC,Silink M

    更新日期:2016-08-01 00:00:00

  • Obesity and family history of diabetes as risk factors of impaired fasting glucose: implications for the early detection of prediabetes.

    abstract:OBJECTIVE:To determine whether the association between family history of diabetes (FHD) and impaired fasting glucose (IFG) is independent of body mass index (BMI) in children and adolescents. METHODS:In all 443 (11.9%) children and adolescents with FHD, and 3280 (88.1%) without FHD were enrolled in a population-based ...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Rodríguez-Moran M,Guerrero-Romero F,Aradillas-García C,Violante R,Simental-Mendia LE,Monreal-Escalante E,Mendoza Ede L

    更新日期:2010-08-01 00:00:00

  • Practical matters, rather than lack of trust, motivate non-participation in a long-term cohort trial.

    abstract:OBJECTIVE:The objective of this study was to investigate the importance of trust in researchers and other reasons that participating parents, former participants, and non-participants had for participating, or not participating, in a longitudinal cohort study on prediction and development of diabetes in children. STUD...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Helgesson G,Hansson MG,Ludvigsson J,Swartling U

    更新日期:2009-09-01 00:00:00

  • Comparison of the effectiveness of simple carbohydrates on hypoglycemic episodes in children and adolescents with type 1 diabetes mellitus: A randomized study in a diabetes camp.

    abstract:BACKGROUND:Hypoglycemia is the most common and severe complication of insulin treatment during the management of type 1 diabetes mellitus (T1DM). Despite its importance, there is a lack of data about the efficacy and superiority of the carbohydrate sources used in hypoglycemia management in children and adolescents. O...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Erbas IM,Abaci A,Anik A,Simsek E,Tuhan HU,Kocyigit C,Yıldız M,Dundar BN,Bober E,Catli G

    更新日期:2020-07-13 00:00:00

  • Influence of initial insulin dosage on blood glucose dynamics of children and adolescents with newly diagnosed type 1 diabetes mellitus.

    abstract:OBJECTIVE:To investigate the effect of initial insulin dosage on blood glucose (BG) dynamics, β-cell protection, and oxidative stress in type 1 diabetes mellitus. METHODS:Sixty newly diagnosed type 1 diabetes mellitus patients were randomly assigned to continuous subcutaneous insulin infusions of 0.6 ± 0.2 IU/kg/d (gr...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章,随机对照试验


    authors: Wang Y,Gong C,Cao B,Meng X,Wei L,Wu D,Liang X,Li W,Liu M,Gu Y,Su C

    更新日期:2017-05-01 00:00:00

  • Presentation of youth with type 2 diabetes in the Pediatric Diabetes Consortium.

    abstract:OBJECTIVE:Type 2 diabetes (T2D) in youth is recognized as a pediatric disease, but few reports describe the characteristics during diagnosis. We describe the clinical presentation of 503 youth with T2D. METHODS:The Pediatric Diabetes Consortium (PDC) T2D Clinic Registry enrolled T2D participants from eight pediatric d...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章,多中心研究


    authors: Klingensmith GJ,Connor CG,Ruedy KJ,Beck RW,Kollman C,Haro H,Wood JR,Lee JM,Willi SM,Cengiz E,Tamborlane WV,Pediatric Diabetes Consortium.

    更新日期:2016-06-01 00:00:00

  • Management of cardiovascular disease risk in teens with type 1 diabetes: Perspectives of teens with and without dyslipidemia and parents.

    abstract::Hypertension and dyslipidemia are often suboptimally managed in teens with type 1 diabetes (T1D). Teen and parent perspectives on hypertension and dyslipidemia management need further study to enhance the development of cardiovascular disease (CVD) risk factor management plans. We sought to describe barriers to and st...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Katz ML,Guo Z,Cheema A,Laffel LM

    更新日期:2019-03-01 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

  • Maternal diabetes distress is linked to maternal depressive symptoms and adolescents' glycemic control.

    abstract:OBJECTIVE:Mothers of youth with type 1 diabetes experience increased levels of stress and depression related to the burden of diabetes management, but the concept of diabetes distress, or distress linked specifically to diabetes and its management, has not been applied to mothers. The current study examined diabetes di...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Rumburg TM,Lord JH,Savin KL,Jaser SS

    更新日期:2017-02-01 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

  • Plasma insulin levels in childhood are related to maternal factors--results of the Ulm Birth Cohort Study.

    abstract:AIMS:The cardiovascular risk factor profile of a child as well as the development of body weight are influenced by genetic and childhood factors. Circulating insulin concentrations reflect the metabolic cardiovascular risk and may trigger weight gain. We aimed at identifying parental and childhood factors which may inf...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Brandt S,Moß A,Lennerz B,Koenig W,Weyermann M,Rothenbacher D,Brenner H,Wabitsch M

    更新日期:2014-09-01 00:00:00

  • Corticotropic axis drive of overnight cortisol secretion is suppressed in adolescents and young adults with type 1 diabetes mellitus.

    abstract:CONTEXT:Type 1 diabetes mellitus (T1DM) is a pro-inflammatory stress state, which, with its attendant hyperglycemia, likely disrupts hypothalamo-pituitary-adrenal (HPA) control, further dysregulating glucose homeostasis. OBJECTIVE:To test the hypothesis that endogenous adrenocorticotropic hormone (ACTH)-cortisol dose-...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Sharma AN,Wigham J,Veldhuis JD

    更新日期:2014-09-01 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

  • Treatment options for type 2 diabetes in adolescents and youth: a study of the comparative efficacy of metformin alone or in combination with rosiglitazone or lifestyle intervention in adolescents with type 2 diabetes.

    abstract::Despite the increased prevalence of type 2 diabetes mellitus (T2DM) in the pediatric population, there is limited information about the relative effectiveness of treatment approaches. This article describes the rationale and design of a National Institutes of Health-sponsored multi-site, randomized, parallel group cli...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: TODAY Study Group.,Zeitler P,Epstein L,Grey M,Hirst K,Kaufman F,Tamborlane W,Wilfley D

    更新日期:2007-04-01 00:00:00

  • Sweet dreams?--nocturnal hypoglycemia in children with type 1 diabetes.

    abstract::Hypoglycemia is an inevitable consequence of the treatment of type 1 diabetes in childhood. Nocturnal hypoglycemia is often considered as merely the submerged part of this serious complication yet there are reasons to believe that hypoglycemia occurring during sleep may be different in physiological terms. Glucose hom...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Matyka KA

    更新日期:2002-06-01 00:00:00

  • Pathogenicity of a glucokinase gene mutation and description of its clinical phenotype.

    abstract::Glucokinase gene (GCK) mutations comprise approximately 10% of cases of maturity-onset diabetes of the young (MODY). Over 800 different mutations in GCK have been reported in the Human Gene Mutation Database, the vast majority of which result in MODY type 2. The missense mutation p.Leu122Val is listed in that database...

    journal_title:Pediatric diabetes



    authors: Hunter JD,Staton H,Constantacos C,Walsh ET,Crudo DF

    更新日期:2020-09-01 00:00:00

  • Bilirubin is an independent factor inversely associated with glycated hemoglobin level in pediatric patients with type 1 diabetes.

    abstract:OBJECTIVE:Bilirubin is a potent antioxidant, and serum total bilirubin (STB) concentrations correlate negatively with cardiovascular risk. In adult diabetic patients and in healthy adults, a negative correlation between STB and glycated hemoglobin (HbA1c) has been reported. We investigated whether there is such an asso...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Mianowska B,Kamińska A,Fendler W,Szadkowska A,Młynarski W

    更新日期:2014-08-01 00:00:00

  • Infant anthropometry, early life infection, and subsequent risk of type 1 diabetes mellitus: a prospective birth cohort study.

    abstract:BACKGROUND:Higher birthweight is associated with increased type 1 diabetes mellitus (T1DM) risk, but the contribution of higher adiposity or lean mass is unclear. In this Tasmanian infant cohort, early upper respiratory infection has been associated with higher asthma risk. PATIENTS AND METHODS:Eligible infants repres...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章,多中心研究


    authors: Ponsonby AL,Pezic A,Cochrane J,Cameron FJ,Pascoe M,Kemp A,Dwyer T

    更新日期:2011-06-01 00:00:00

  • Alterations in left ventricular, left atrial, and right ventricular structure and function to cardiovascular risk factors in adolescents with type 2 diabetes participating in the TODAY clinical trial.

    abstract::Data on cardiovascular disease (CVD) risk in adolescents with type 2 diabetes (T2D) are limited. Echocardiography was performed in the last year of the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) clinical trial (median 4½ yr from diagnosis of T2D, average age 18 yr), including MMode and 2D m...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章,多中心研究,随机对照试验


    authors: Levitt Katz L,Gidding SS,Bacha F,Hirst K,McKay S,Pyle L,Lima JA,TODAY Study Group.

    更新日期:2015-02-01 00:00:00

  • Instability of different adolescent metabolic syndrome definitions tracked into early adulthood metabolic syndrome: Tehran Lipid and Glucose Study (TLGS).

    abstract:BACKGROUND AND OBJECTIVE:There are substantial controversies about the clinical utility of adolescent metabolic syndrome (MetS). The current study examined the stability of adolescent MetS by assessing the agreement and discriminative abilities of four different definitions of adolescent MetS and the adult MetS definit...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Asghari G,Eftekharzadeh A,Hosseinpanah F,Ghareh S,Mirmiran P,Azizi F

    更新日期:2017-02-01 00:00:00

  • Changes to Care Delivery at Nine International Pediatric Diabetes Clinics in Response to the COVID-19 Global Pandemic.

    abstract:BACKGROUND:Pediatric diabetes clinics around the world rapidly adapted care in response to COVID-19. We explored provider perceptions of care delivery adaptations and challenges for providers and patients across nine international pediatric diabetes clinics. METHODS:Providers in a quality improvement collaborative com...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Cristello Sarteau A,Souris KJ,Wang J,Ramadan AA,Addala A,Bowlby D,Corathers S,Forsander G,King B,Law JR,Liu W,Malik F,Pihoker C,Seid M,Smart C,Sundberg F,Tandon N,Yao M,Headley T,Mayer-Davis E

    更新日期:2021-01-19 00:00:00

  • Improvement in glycemic control through changes in insulin regimens: findings from a Japanese cohort of children and adolescents with type 1 diabetes.

    abstract:OBJECTIVE:Although insulin analogs have dramatically changed diabetes treatment, scarce evidence is available on those effects. We aimed to explore whether glycemic control had improved, the use of insulin analogs had been increased, and hypoglycemic events had decreased over time in Japanese pediatric patients with ty...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Mochizuki M,Kikuchi T,Urakami T,Kikuchi N,Kawamura T,Yokomichi H,Hoshino T,Matsuura N,Sasaki N,Sugihara S,Amemiya S,Japanese Study Group of Insulin Therapy for Childhood Adolescent Diabetes (JSGIT).

    更新日期:2017-09-01 00:00:00

  • Eligibility for clinical trials is limited for youth with type 2 diabetes: Insights from the Pediatric Diabetes Consortium T2D Clinic Registry.

    abstract:BACKGROUND/OBJECTIVE:Restrictive eligibility criteria have hampered enrollment into trials for new drugs for youth with type 2 diabetes (T2D). We utilized Pediatric Diabetes Consortium (PDC) T2D Registry enrollment data to estimate the percentage of patients who would be excluded from current T2D trials based on out-of...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Tamborlane WV,Chang P,Kollman C,Klingensmith GJ,Ruedy K,Gal RL,Van Name M,Bacha F,Willi S,Beck RW,Pediatric Diabetes Consortium.

    更新日期:2018-12-01 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

  • Two's company, is three a crowd? Ethical cognition in decision making and the role of industry third parties in pediatric diabetes care.

    abstract::Families of children with diabetes increasingly obtain health information from a variety of sources. Doctor-patient relationships have accordingly become more fluid and dynamic with input from other parties. These outside parties include representatives from the diabetes health care industry-industry third parties (IT...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章,评审


    authors: Cameron FJ,Moore B,Gillam L

    更新日期:2019-02-01 00:00:00

  • Benefit of supplementary fat plus protein counting as compared with conventional carbohydrate counting for insulin bolus calculation in children with pump therapy.

    abstract:OBJECTIVE:To investigate carbohydrate (CARB) and supplementary fat/protein (CFP) counting using normal and dual-wave bolus in pump therapy of children and young people with type 1 diabetes (T1D). STUDY DESIGN AND METHODS:A randomized clinical trial was conducted in 42 patients (age 6-21 yr) with T1D for at least 1 yr ...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章,随机对照试验


    authors: Kordonouri O,Hartmann R,Remus K,Bläsig S,Sadeghian E,Danne T

    更新日期:2012-11-01 00:00:00

  • Measurement of diabetes stress in older children and adolescents with type 1 diabetes mellitus.

    abstract:OBJECTIVE:Studies indicate general psychological stress plays a role in the glycemic control of individuals with type 1 diabetes mellitus (T1DM). Disease-specific rather than general measures may be more closely related to measures of health outcomes. Therefore, measurement of diabetes-related stress is needed to advan...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Delamater AM,Patiño-Fernández AM,Smith KE,Bubb J

    更新日期:2013-02-01 00:00:00

  • School-aged children with type 1 diabetes benefit more from a coping skills training program than adolescents in China: 12-month outcomes of a randomized clinical trial.

    abstract:BACKGROUND:Managing type 1 diabetes can be challenging, especially for youth, so there is a need for effective interventions to help youth live with diabetes. OBJECTIVE:To determine the efficacy of a coping skills training (CST) program for Chinese youth with type 1 diabetes and to explore whether the efficacy of the ...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Guo J,Luo J,Yang J,Huang L,Wiley J,Liu F,Li X,Zhou Z,Whittemore R

    更新日期:2020-05-01 00:00:00

  • Worldwide childhood type 1 diabetes incidence--what can we learn from epidemiology?

    abstract::Type 1 diabetes is the most common form of diabetes in most part of the world, although reliable data are still unavailable in several countries. Wide variations exist between the incidence rates of different populations, incidence is lowest in China and Venezuela (0.1 per 100,000 per year) and highest in Finland and ...

    journal_title:Pediatric diabetes

    pub_type: 杂志文章


    authors: Soltesz G,Patterson CC,Dahlquist G,EURODIAB Study Group.

    更新日期:2007-10-01 00:00:00