Extended Family History of Type 1 Diabetes and Phenotype and Genotype of Newly Diagnosed Children

Parkkola, Anna; Härkönen, Taina; Ryhänen, Samppa J.; Ilonen, Jorma; Knip, Mikael

doi:10.2337/dc12-0445

Cited by 89 publications

(95 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…To further characterize the effects of a positive family history of AIDs, we grouped the index children into autoimmune families, in which autoimmunity was truly clustered, and accordingly, differences in pathogenetic mechanisms should be evident. The only significant difference observed, however, was the milder metabolic decompensation at diagnosis among the children from autoimmune families, which is probably due to the effect of familial diabetes and the earlier recognition of symptoms in such families (29). These findings do not consistently support the hypothesis of different pathogenetic mechanisms of diabetes operating in families with clustered autoimmunity.…”

Section: Discussionmentioning

confidence: 61%

“…This could reflect the increased genetic risk of autoimmunity in the relatives of mothers or a recollection bias in the form of mothers being more aware than fathers of the diseases diagnosed in their relatives. Interestingly, in the same dataset, such a difference was not observed for T1D; it was reported equally often in maternal (6.5%) and paternal (6.0%) second-degree relatives, but was more common in fathers (6.2%) than in mothers (3.2%) (29). This emphasizes the differential sex distributions and possible sex-dependent inheritance patterns in T1D and other AIDs.…”

Section: Discussionmentioning

confidence: 63%

“…The register contains information on the family history of AIDs collected by a structured questionnaire (29). The families are asked to list any family members with AIDs, and the following examples are given: CD, dermatitis herpetiformis, AIT, autoimmune adrenal dysfunction, rheumatoid arthritis, multiple sclerosis, pernicious anemia, and systemic lupus erythematosus.…”

Section: Study Design and Subjectsmentioning

confidence: 99%

See 2 more Smart Citations

Extended family history of autoimmune diseases and phenotype and genotype of children with newly diagnosed type 1 diabetes

Parkkola

Härkönen

Ryhänen

et al. 2013

European Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

Objective: Based on the concept of clustering autoimmunity, children with a positive family history of autoimmunity could be expected to have a different pathogenetic form of type 1 diabetes (T1D) and thus a stronger autoimmune reactivity against b-cells and an increased prevalence of the HLA-DR3-DQ2 haplotype.Design and methods: We tested this hypothesis in a cross-sectional observational study from the Finnish Pediatric Diabetes Register. HLA class II genotypes and b-cell autoantibodies were analyzed, and data on the extended family history of autoimmunity and clinical markers at diagnosis were collected with a structured questionnaire from 1488 children diagnosed with T1D under the age of 15 years (57% males). Results: Only 23 children (1.5%) had another autoimmune disease (AID) known at diagnosis, and they had a milder metabolic decompensation at diabetes presentation. One-third (31.4%) had at least one relative with an AID other than T1D with affected mothers being overrepresented (8.2%) compared with fathers (2.8%). The children with a positive family history of other AIDs had higher levels of islet cell antibodies (PZ0.003), and the HLA-DR3-DQ2 haplotype in the children was associated with celiac disease in the extended family (P!0.001), but not with an increased frequency of autoimmune disorders, in general.Conclusions: Approximately one-third of children with newly diagnosed T1D have a first-and/or second-degree relative affected by an AID. Our data do not consistently support the hypothesis of differential pathogenetic mechanisms in such children.

show abstract

Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 63%

Section: Study Design and Subjectsmentioning

confidence: 99%

See 1 more Smart Citation

Extended family history of autoimmune diseases and phenotype and genotype of children with newly diagnosed type 1 diabetes

Parkkola

Härkönen

Ryhänen

et al. 2013

European Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

show abstract

“…A recent study on the Finnish population [2] reported that 12.2 % of the newly diagnosed T1DM children had a 1st degree relative with T1DM and 11.9 % had an affected 2nd degree relative. Children without affected relatives had lower pH, higher plasma glucose and a higher rate of impaired consciousness, and more relevant weight loss at T1DM onset.…”

Section: Discussionmentioning

confidence: 99%

Family history and ethnicity influencing clinical presentation of type 1 diabetes in childhood

Bizzarri

Paladini²,

Benevento

et al. 2015

J Endocrinol Invest

View full text Add to dashboard Cite

The milder metabolic decompensation in children with a positive family history of T1DM is probably explained by the awareness of the families in terms of early symptoms of T1DM, while the younger age at onset and the higher levels of autoantibodies may suggest a stronger genetic susceptibility, associated with a more aggressive autoimmune process. The younger age in non-Caucasian children is probably explained by the higher genetic susceptibility in subjects belonging to ethnic groups with a low T1DM incidence. Social aspects and poor living conditions probably predominate in determining the increased severity of metabolic decompensation at onset in children from non-Caucasian ethnicities.

show abstract

“…The intervention proved to have no effect on the progression to T1D (13). Cases with T1D were diagnosed by the World Health Organization (WHO) criteria (14) and ascertained from the patient records of the University Hospitals of Turku, Oulu, and Tampere, and from the National Diabetes Register (15). Follow-up for T1D continued until the end of October 2012.…”

Section: Subjects and Study Designmentioning

confidence: 99%

Insulin secretion and sensitivity in the prediction of type 1 diabetes in children with advanced β-cell autoimmunity

Siljander

Hermann

Hekkala

et al. 2013

European Journal of Endocrinology

Self Cite

View full text Add to dashboard Cite

Objective: Reduced early insulin response has been shown to predict type 1 diabetes (T1D) in firstdegree relatives of diabetic patients, while its role, as well as that of insulin resistance, has remained poorly defined in young children representing the general population. The predictive values of these markers and their relation to other risk factors of T1D were assessed in children with advanced b-cell autoimmunity, i.e. persistent positivity for two or more autoantibodies. Design and methods: Intravenous glucose tolerance tests (IVGTTs) were carried out in 218 children with HLA-DQB1-conferred disease susceptibility and advanced b-cell autoimmunity. Baseline, metabolic and growth data were compared between children progressing to diabetes and those remaining unaffected. Hazard ratios for the disease predictors and the progression rate of T1D were assessed. Results: Children developing T1D were younger at seroconversion, progressed more rapidly to advanced b-cell autoimmunity and had lower first-phase insulin response (FPIR) and homeostasis model assessment index for insulin resistance (HOMA-IR) than those remaining non-diabetic. The levels of HOMA-IR/FPIR, islet cell antibodies, insulin autoantibodies (IAA) and islet antigen 2 antibodies (IA-2A) were higher in progressors. BMI SDS, FPIR, age at IVGTT and levels of IAA and IA-2A were predictive markers for T1D. Conclusions: Young age, higher BMI SDS, reduced FPIR and higher levels of IAA and IA-2A predicted T1D in young children with HLA-DQB1-conferred disease susceptibility and advanced b-cell autoimmunity. Disease risk estimates were successfully stratified by the assessment of metabolic status and BMI. The role of insulin resistance as an accelerator of the disease process was minor.

show abstract

Extended Family History of Type 1 Diabetes and Phenotype and Genotype of Newly Diagnosed Children

Cited by 89 publications

References 33 publications

Extended family history of autoimmune diseases and phenotype and genotype of children with newly diagnosed type 1 diabetes

Extended family history of autoimmune diseases and phenotype and genotype of children with newly diagnosed type 1 diabetes

Family history and ethnicity influencing clinical presentation of type 1 diabetes in childhood

Insulin secretion and sensitivity in the prediction of type 1 diabetes in children with advanced β-cell autoimmunity

Contact Info

Product

Resources

About