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

Abstract

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,

Familial autoimmunity in pediatric patients with type 1 diabetes (T1D) and its associations with the severity of clinical presentation at diabetes diagnosis and with coexisting autoimmunity

“…The latter observation is in accordance with the existing literature, indicating that genetic factors may play a significant role in the pathogenesis of T1D, resulting in a more aggressive autoimmune process [12,21,[25][26][27]. On the other hand, multifactorial logistic regression analysis of our data showed that the presence of T1D family history acted protectively against DKA manifestation due to timely diagnosis.…”

“…Children with a firstdegree relative with autoimmune disease had a three-fold higher risk of experiencing a second autoimmune disease during the course of T1D, independently of the patient's age or the duration of the disease (OR:2.72, p = 0.021). Additionally, children with coexisting autoimmunity had a higher proportion (i.e., > 3) of relatives with autoimmunity compared to the rest of the study group (p = 0.026), this being in accordance with previous reports [12,25,31]. A thorough follow-up that includes monitoring for possible coexisting autoimmune diseases is recommended in T1D patients, especially those with a family history of autoimmunity and prompt advice should be offered to the relatives of these patients concerning the higher risk for development of an autoimmune disease in the future.…”

“…Our findings are in accordance with previous reports in the international literature. [12,19] In particular, the study patients with familial type T1D were diagnosed at a younger age, while they had lower HbA1c levels, lower prevalence of DKA at diagnosis, and higher prevalence of associated autoimmune diseases compared to those with sporadic T1D [12].…”

“…We also evaluated the correlation of familial autoimmunity with laboratory parameters (c-peptide and pancreatic autoantibodies), as well as its association with the development of additional autoimmune diseases in the patients. There are very few studies to date assessing the frequencies of familial autoimmune diseases in the relatives of children and adolescents with T1D, and, to our knowledge, only one of them has reported on its association with the presence and severity of DKA at diagnosis of diabetes or pancreatic autoimmunity [12]. Several common genetic loci along with environmental factors can predispose to the manifestation of either a specific type or a spectrum of autoimmune diseases within the members of the family [13].…”

Pädiatrie aktuell – Forschung kurz notiert

“…Eine deutsch-österreichische Multizenteranalyse [ 4 ] vergleicht ausgewählte Parameter bei familiärem vs. sporadischem Diabetes für den Zeitraum 1995–2018. Im Rahmen des Diabetes Prospective Follow-up Registry (DPV) wurden 57.371 Patienten mit Diabetes Typ 1 erfasst, davon waren 93,4 % sporadische Fälle, 6,6 % familiäre Fälle (zumindest ein Verwandter 1.…”