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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.

Project description:AimThere are increasing evidence demonstrating that neutrophil-mediated inflammation plays a role in the etiology of type 2 diabetes. However, the molecular mechanisms by which neutrophils contribute to type 2 diabetes remain largely unknown. The aim of the present work was to identify possible changes in circulating neutrophils to better elucidate neutrophil involvement in human type 2 diabetes.MethodsPatients newly diagnosed with type 2 diabetes (n = 5) and age- and sex-matched healthy controls (n = 5) were recruited. Neutrophils were purified from type 2 diabetes patients and controls, and RNA sequencing (RNA-seq) was used for comprehensive transcriptome analysis. Differentially expressed genes (DEGs) were screened, and Gene Ontology (GO) and KEGG pathway enrichment analyses were performed. Real-time polymerase chain reaction (qPCR) was used for validation in external samples of type 2 diabetes patients (n = 8) and healthy controls (n = 8).ResultsGene expression analysis showed that, compared with neutrophils from healthy controls, there were 1990 upregulated DEGs and 1314 downregulated DEGs in neutrophils from type 2 diabetes patients. GO analysis demonstrated that the DEGs were mainly involved in myeloid leukocyte activation, T cell activation, adaptive immunity, and cytokine production. The top 20 enriched KEGG pathways included the cytokine-cytokine receptor interaction pathway, NF-?B signaling pathway, cell adhesion molecules, and chemokine signaling pathway. Furthermore, qPCR of genes related to neutrophil activation revealed that the expression of SELL, SELP, CXCR1, and S100A8 was significantly increased in neutrophils from type 2 diabetes patients compared with that in neutrophils from controls.ConclusionsOur study reveals an abnormal activation of circulating neutrophils at the transcriptome level in type 2 diabetes patients. These findings suggest a potential involvement of neutrophil dysfunction in the pathologic process of type 2 diabetes and provide insight into potential therapeutic targets for type 2 diabetes.

Project description:ObjectivesTo assess the long term clinical and cost effectiveness of the diabetes education and self management for ongoing and newly diagnosed (DESMOND) intervention compared with usual care in people with newly diagnosed type 2 diabetes.DesignWe undertook a cost-utility analysis that used data from a 12 month, multicentre, cluster randomised controlled trial and, using the Sheffield type 2 diabetes model, modelled long term outcomes in terms of use of therapies, incidence of complications, mortality, and associated effect on costs and health related quality of life. A further cost-utility analysis was also conducted using current "real world" costs of delivering the intervention estimated for a hypothetical primary care trust.SettingPrimary care trusts in the United Kingdom.ParticipantsPatients with newly diagnosed type 2 diabetes.InterventionA six hour structured group education programme delivered in the community by two professional healthcare educators.Main outcome measuresIncremental costs and quality adjusted life years (QALYs) gained.ResultsOn the basis of the data in the trial, the estimated mean incremental lifetime cost per person receiving the DESMOND intervention is pound209 (95% confidence interval - pound704 to pound1137; euro251, -euro844 to euro1363; $326, -$1098 to $1773), the incremental gain in QALYs per person is 0.0392 (-0.0813 to 0.1786), and the mean incremental cost per QALY is pound5387. Using "real world" intervention costs, the lifetime incremental cost of the DESMOND intervention is pound82 (- pound831 to pound1010) and the mean incremental cost per QALY gained is pound2092. A probabilistic sensitivity analysis indicated that the likelihood that the DESMOND programme is cost effective at a threshold of pound20 000 per QALY is 66% using trial based intervention costs and 70% using "real world" costs. Results from a one way sensitivity analysis suggest that the DESMOND intervention is cost effective even under more modest assumptions that include the effects of the intervention being lost after one year.ConclusionOur results suggest that the DESMOND intervention is likely to be cost effective compared with usual care, especially with respect to the real world cost of the intervention to primary care trusts, with reductions in weight and smoking being the main benefits delivered.

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

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

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