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Extended family history of type 1 diabetes and phenotype and genotype of newly diagnosed children.

ABSTRACT: OBJECTIVE: To determine the frequency of newly diagnosed diabetic children with first- and second-degree relatives affected by type 1 diabetes and to characterize the effects of this positive family history on clinical markers, signs of ?-cell autoimmunity, and HLA genotype in the index case. RESEARCH DESIGN AND METHODS: Children (n = 1,488) with type 1 diabetes diagnosed under 15 years of age were included in a cross-sectional study from the Finnish Pediatric Diabetes Register. Data on family history of diabetes and metabolic decompensation at diagnosis were collected using a questionnaire. Antibodies to ?-cell autoantigens (islet cell antibodies, insulin autoantibodies, GAD antibodies, and antibodies to the islet antigen 2 molecule) and HLA genotypes were analyzed. RESULTS: A total of 12.2% of the subjects had a first-degree relative with type 1 diabetes (father 6.2%, mother 3.2%, and sibling 4.8%) and 11.9% had an affected second-degree relative. Children without affected relatives had lower pH (P < 0.001), higher plasma glucose (P < 0.001) and ?-hydroxybutyrate concentrations (P < 0.001), a higher rate of impaired consciousness (P = 0.02), and greater weight loss (P < 0.001). There were no differences in signs of ?-cell autoimmunity. The familial cases carried the HLA DR4-DQ8 haplotype more frequently than sporadic cases (74.0 vs. 67.0%, P = 0.02). CONCLUSIONS: When the extended family history of type 1 diabetes is considered, the proportion of sporadic diabetes cases may be reduced to <80%. A positive family history for type 1 diabetes associates with a less severe metabolic decompensation at diagnosis, even when only second-degree relatives are affected. Autoantibody profiles are similar in familial and sporadic type 1 diabetes, suggesting similar pathogenetic mechanisms.

SUBMITTER: Parkkola A

PROVIDER: S-EPMC3554291 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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Extended family history of type 1 diabetes and phenotype and genotype of newly diagnosed children.

Parkkola Anna A Härkönen Taina T Ryhänen Samppa J SJ Ilonen Jorma J Knip Mikael M

Diabetes care 20121001 2

<h4>Objective</h4>To determine the frequency of newly diagnosed diabetic children with first- and second-degree relatives affected by type 1 diabetes and to characterize the effects of this positive family history on clinical markers, signs of β-cell autoimmunity, and HLA genotype in the index case.<h4>Research design and methods</h4>Children (n = 1,488) with type 1 diabetes diagnosed under 15 years of age were included in a cross-sectional study from the Finnish Pediatric Diabetes Register. Dat ...[more]

PMID: 23033245

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Project description:ObjectiveTo investigate the association between a parental and/or sibling history of diabetes and clinical characteristics.DesignA cross-sectional study.SettingThe data were collected from the endocrinology department of The Second Xiangya Hospital of Central South University from June 2017 to October 2019.ParticipantsA total of 894 newly diagnosed patients with type 2 diabetes were recruited. Data on clinical characteristics were collected from patient medical records. Pancreatic β-cell function and insulin resistance were calculated with the homeostatic model assessment. SPSS V.25.0 was used to perform the analysis.ResultsThe percentages of patients with parental and sibling histories of diabetes were 14.8% and 9.8%, respectively. The prevalence of diabetic ketoacidosis (DKA) was 3.9%. Compared with those with no parental history of diabetes, patients with a parental history of diabetes were characterised by early-onset disease (41.70±10.88 vs 51.17±14.09 years), poor glycaemic control of fasting blood glucose (10.84±5.21 vs 8.91±4.38 mmol/L) and a high prevalence of DKA (7.6% vs 3.3%). The patients with a sibling history of diabetes had later disease onset (56.05±9.86 vs 49.09±14.29 years) and lower BMI (24.49±3.48 vs 25.69±3.86 kg/m2) than those with no sibling history of diabetes. Univariate regression suggested that both parental history (p=0.037) and sibling history (p=0.011) of diabetes were associated with β-cell function; however, multiple regression analysis showed that only a sibling history of diabetes was associated with β-cell function (p=0.038). Univariate regression revealed a positive correlation between parental history of diabetes (p=0.023, OR=2.416, 95% CI 1.132 to 5.156) and DKA. Unfortunately, this correlation was not statistically significant for either patients with a parental history (p=0.234, OR=1.646, 95% CI 0.724 to 3.743) or those with a sibling history (p=0.104, OR=2.319, 95% CI 0.841 to 6.389) after adjustments for confounders.ConclusionA sibling history of diabetes was associated with poor β-cell function, and a parental history of diabetes was associated with poor glycaemic control and a high prevalence of DKA.

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Extended family history of type 1 diabetes and phenotype and genotype of newly diagnosed children.

Publications

Extended family history of type 1 diabetes and phenotype and genotype of newly diagnosed children.

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