The proportion of familial cases of type 1 diabetes is increasing simultaneously with the disease incidence: Eighteen years of the Israeli Pediatric Diabetes Registry

Zung, Amnon; Na’amnih, Wasef; Bluednikov, Yulia; Mery, Nisim; Blumenfeld, Orit

doi:10.1111/pedi.12617

Cited by 3 publications

(2 citation statements)

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“…Familial type 1 diabetes in this study was characterized by younger age at onset and higher prevalence of associated autoimmune disease in comparison with sporadic type 1 diabetes. The results differ from earlier reports describing similar ages in sporadic and familial cases in smaller populations (2,4,5,20) but are in accordance with previous observations in twins and siblings identifying young age at onset in the first sibling as a major risk factor for type 1 diabetes in the second sibling (3,(21)(22)(23). Higher autoimmune comorbidity, early disease manifestation, and short time between diagnoses in the first and second family member observed in the current study support the notion that patients with familial diabetes share higher HLA-associated and other genetic (21) and environmental (24) risks compared with patients with sporadic type 1 diabetes, leading to an accelerated immune-mediated disease.…”

Section: Discussioncontrasting

confidence: 99%

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A Comparison of Familial and Sporadic Type 1 Diabetes Among Young Patients

et al. 2020

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To investigate natural course, treatment, and outcomes in familial versus sporadic type 1 diabetes. RESEARCH DESIGN AND METHODSIn a population-based study, we compared patients with onset of type 1 diabetes before the age of 20 years who had a first-degree relative with type 1 diabetes (familial diabetes) with patients with type 1 diabetes who had no first-degree relative with type 1 diabetes (sporadic diabetes) at diagnosis and over the first 10 treatment years, using multivariable regression and proportional hazards models. Patients were identified from the Diabetes Prospective Follow-up Registry (DPV) between 1995 and 2018. RESULTSOf 57,371 patients with type 1 diabetes, 53,606 (93.4%) had sporadic diabetes and 3,765 (6.6%) had familial diabetes. Familial diabetes, compared with sporadic diabetes, was associated with younger age (median 7.9 vs. 9.7 years, P < 0.001), lower prevalence of ketoacidosis (11.9% vs. 20.4%, P < 0.001), and lower HbA 1c levels (9.7% vs. 11.1%, P < 0.001) at onset and higher prevalence of associated autoimmune disease (16.7% vs. 13.6%, P < 0.001). Over 10 years, patients with familial diabetes, in comparison with sporadic diabetes, more often used insulin pumps (P < 0.001) and had a lower rate of severe hypoglycemia (12.97 vs. 14.44 per 100 patient-years, P < 0.001) but similar HbA 1c levels (P ‡ 0.08) and ketoacidosis rates (1.85 vs. 2.06 per 100 patient-years, P = 0.11). In familial and sporadic diabetes, absence of ketoacidosis at onset predicted fewer events of severe hypoglycemia (hazard ratio [HR] 0.67, P < 0.001, and 0.91, P < 0.001, respectively) and of ketoacidosis (HR 0.64, P 5 0.007, and 0.66, P < 0.001, respectively) after 10 years. CONCLUSIONSFamilial type 1 diabetes, compared with sporadic type 1 diabetes, is characterized by earlier disease manifestation and higher autoimmune comorbidity as well as less metabolic decompensation at onset, likely related to higher disease awareness in affected families, while the course of disease is similar. These findings may have implications for the generalizability of results of diabetes prevention trials from patients with familial type 1 diabetes to patients with sporadic type 1 diabetes.The prevalence of familial type 1 diabetes varies, with estimates ranging from 5% (1) to 12.2% (2) depending on the population investigated, the length of observation,

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Section: Discussioncontrasting

confidence: 99%

“…and the study setting (3)(4)(5)(6). Those with familial diabetes carry the risk haplotype DR4-DQ8 more often than those with sporadic diabetes (2,4) indicating that HLA-associated genetic risk might play a role in familial clustering of the disease.…”

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confidence: 99%