Published on Mar 6, 2012; Accepted on Jul 26, 2012; Released on Feb, 2013.
This study aims to investigate the relationship between extended family history of type 1 diabetes and the phenotype and genotype of newly diagnosed children. By examining the genetic factors contributing to the development of diabetes within families, researchers hope to gain a better understanding of the hereditary nature of the disease.
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Abstract
OBJECTIVE
An examination into the occurrence of recently diagnosed diabetic children with affected relatives with type 1 diabetes and the implications on clinical indicators, signs of β-cell autoimmunity, and HLA genetics in the central case.
RESEARCH DESIGN AND METHODS
The investigation encompassed children (n = 1,488) with type 1 diabetes below 15 years old identified from the Finnish Pediatric Diabetes Register. Details on the family history of diabetes and metabolic imbalances at the time of diagnosis were gathered. Analysis was carried out on antibodies to β-cell autoantigens and HLA genotypes.
RESULTS
CONCLUSIONS
The clustering of type 1 diabetes within families raises the risk for contracting the disease, with most diagnosed children being isolated cases. The fraction of children with affected relatives upon diagnosis is approximately 10-12%, and this ratio grows over time. Paternal transmission of the disease appears to be more prevalent than maternal.
RESEARCH DESIGN AND METHODS
Subjects
Starting from 2002, the Finnish Pediatric Diabetes Register requested all juvenile patients diagnosed with diabetes to participate. Around 70% contributed blood samples for autoantibodies and HLA-DR-DQA1-DQB1 haplotypes.
Participants in the register received a survey concerning clinical condition, metabolic decompensation at diagnosis, and family background of diabetes. Legal guardians and siblings of the children provided their consent for participation.
By 2006, the register enrolled 2,663 children with type 1 diabetes, with 1,488 meeting the study criteria.
Most children had blood samples taken within 5 days of diagnosis. Levels of insulin antibodies were linked to the autoimmune response.
Autoantibodies
Autoantibodies were examined using established methods with specific thresholds for positivity. Sensitivity and specificity of antibodies were determined based on a control group.
HLA typing
HLA typing was carried out for the majority of the central cases to assess major DR-DQ haplotypes.
Markers of metabolic decompensation at diagnosis
At diagnosis, blood pH, plasma glucose, and β-hydroxybutyrate levels in the children were assessed in local labs. Due to discrepancies in methods across labs, Hemoglobin A1c was not measured.
Statistical analyses relied on SPSS software, encompassing cross-tabulation, χ 2 stats, Fisher exact test, Student t-test, one-way ANOVA, Mann-Whitney U test, Wilcoxon rank sums test, and Kruskal-Wallis test with Dunn post hoc test. A significance value of 0.05 or less was acknowledged.
Central cases ranged from 0.28 to 14.99 years at diagnosis. A majority were male, with many having at least one sibling. A small fraction had relatives with type 1 diabetes.
21.8% of children had an affected relative among first and/or second-degree relatives. There were no variations in age at diagnosis among comparison groups.
Children with familial type 1 diabetes exhibited genetic markers more frequently. No significant differences were noted in autoantibody levels between groups.
This investigation offers insights into familial and non-familial type 1 diabetes cases. Reports point to an increased presence of fathers with type 1 diabetes. No conclusive evidence supporting preferential transmission patterns was found due to limited analysis capabilities.
On the whole, this study illuminates the distribution and genetic elements in type 1 diabetes cases within families.
Individuals with a family history of type 1 diabetes experienced a less severe metabolic imbalance at diagnosis compared to isolated cases. This can be attributed to the heightened awareness of parents regarding early symptoms, resulting in a swifter diagnosis and treatment. Families with a history of type 1 diabetes also displayed an enhancement in metabolic status at diagnosis. A minority of children with type 1 diabetes having affected relatives in both first- and second-degree showed even milder metabolic imbalances at diagnosis than those with only one affected family member. This emphasizes the accumulated knowledge of the disease within these families.
Research indicates comparable frequencies or levels of disease-related autoantibodies in cases of both sporadic and familial type 1 diabetes, suggesting similar pathological mechanisms. Genetic variations, such as the DR4-DQ8 haplotype, were observed between familial and sporadic cases, contributing to the clustering of type 1 diabetes within families.
Challenges in accurate prevalence estimation arise from limited awareness of second-degree relatives and possible recall bias in reporting family history of type 1 diabetes. The absence of a control group in our study restricts direct comparison with the general population. Nevertheless, the observed prevalence of type 1 diabetes among siblings is notably higher than that of the general population.
Supplementary Material
Acknowledgments
Funding for this study was provided by various organizations, and authors disclose no conflicts of interest. Author contributions are clearly outlined, with acknowledgments extended for technical support.
We would like to thank the research participants who volunteered their time and insights for this study. Their contributions were invaluable to the success of our research.
Additionally, we extend our gratitude to the staff members who assisted with data collection and analysis. Their dedication and hard work were essential to the completion of this project.
APPENDIX
The Finnish Pediatric Diabetes Register and Biobank involves a diverse group of researchers and professionals from various medical centers and research institutions in Finland.
Footnotes
*A comprehensive list of researchers from the Finnish Pediatric Diabetes Register can be found in the APPENDIX. For further details and contact information, please refer to the original article.
References
- Familial connection in diabetes mellitus. Exp Clin Endocrinol Diabetes 2007;115:634–640 [DOI] [PubMed] [Google Scholar]
- Type 1 diabetes and multiple sclerosis: a Danish population-based cohort study. Arch Neurol 2006;63:1001–1004 [DOI] [PubMed] [Google Scholar]
- Differential transmission of type 1 diabetes from diabetic fathers and mothers to their offspring. Diabetes 2006;55:1517–1524 [DOI] [PubMed] [Google Scholar]
- Evidence for the importance of gender and birth cohort for risk of IDDM in offspring of IDDM parents. Diabetologia 1995;38:975–982 [DOI] [PubMed] [Google Scholar]
- Family history and risk of type 1 diabetes mellitus. Acta Diabetol 2002;39:111–115 [DOI] [PubMed] [Google Scholar]
- Familial association between type 1 diabetes and autoimmune and related diseases. Diabetologia 2009;52:1820–1828 [DOI] [PubMed] [Google Scholar]
- Risk of diabetes in siblings and other relatives of IDDM subjects. Diabetes 1991;40:831–836 [DOI] [PubMed] [Google Scholar]
- Genetic susceptibility, beta cell autoimmunity, and metabolic characteristics in familial and nonfamilial insulin-dependent diabetes mellitus. Childhood Diabetes in Finland (DiMe) Study Group. J Clin Invest 1996;98:2489–2495 [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
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