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

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posted on 06.04.2021, 22:14 by Beate Karges, Nicole Prinz, Kerstin Placzek, Nicolin Datz, Matthias Papsch, Ursula Strier, Dirk Agena, Walter Bonfig, Heiner Kentrup, Reinhard W. Holl
Objective To investigate natural course, treatment and outcomes in familial versus sporadic type 1 diabetes (T1D).

Research design and methods In a population-based study, we compared patients with onset of T1D before the age of 20 years who had a first-degree relative with T1D (familial diabetes) with patients who had no first-degree relative with T1D (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 (DPV) database between 1995 and 2018.

Results Of 57,371 patients with T1D, 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 HbA1c 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, compared 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 HbA1c 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 0.67, p<0.001, and 0.91, p<0.001, respectively) and of ketoacidosis (hazard ratio 0.64, p=0.007, and 0.66, p<0.001, respectively) after 10 years.

Conclusions Familial T1D, compared with sporadic T1D, 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 familial to sporadic T1D patients.

Funding

This work was supported by the German Center for Diabetes Research (DZD, grant number 82DZD14A02) funded by the Federal Ministry of Education and Research, Berlin, Germany; by the German Diabetes Association; and by the Robert Koch Institute, Berlin, Germany.

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