Beate Karges1,2, Nicole Prinz3,4, Kerstin Placzek5, Nicolin Datz6, Matthias Papsch7, Ursula Strier8, Dirk Agena9, Walter Bonfig10, Heiner Kentrup2, Reinhard W Holl3,4. 1. Division of Endocrinology and Diabetes, Medical Faculty, RWTH Aachen University, Aachen, Germany bkarges@ukaachen.de. 2. Department of Pediatrics, Bethlehem Hospital Stolberg, Stolberg, Germany. 3. Institute of Epidemiology and Medical Biometry, ZIBMT, Ulm University, Ulm, Germany. 4. German Center for Diabetes Research (DZD), Neuherberg, Germany. 5. Department of Pediatrics, Medical Faculty, Martin-Luther University Halle-Wittenberg, Halle (Saale), Germany. 6. Diabetes Center for Children and Adolescents, Children's Hospital Auf der Bult, Hannover, Germany. 7. Department of Neonatology, Pediatric and Adolescent Medicine, Marienhospital Gelsenkirchen, Gelsenkirchen, Germany. 8. Department of Pediatrics, Elisabeth-Krankenhaus Rheydt, Mönchengladbach, Germany. 9. Practice of Pediatrics and Pediatric Diabetes, Hildesheim, Germany. 10. Department of Pediatrics, Klinikum Wels-Grieskirchen, Wels, Austria.
Abstract
OBJECTIVE: To investigate natural course, treatment, and outcomes in familial versus sporadic type 1 diabetes. RESEARCH DESIGN AND METHODS: In 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. RESULTS: Of 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 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, 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 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 [HR] 0.67, P < 0.001, and 0.91, P < 0.001, respectively) and of ketoacidosis (HR 0.64, P = 0.007, and 0.66, P < 0.001, respectively) after 10 years. CONCLUSIONS: Familial 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.
OBJECTIVE: To investigate natural course, treatment, and outcomes in familial versus sporadic type 1 diabetes. RESEARCH DESIGN AND METHODS: In 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. RESULTS: Of 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 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, 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 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 [HR] 0.67, P < 0.001, and 0.91, P < 0.001, respectively) and of ketoacidosis (HR 0.64, P = 0.007, and 0.66, P < 0.001, respectively) after 10 years. CONCLUSIONS: Familial 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.
Authors: Emily K Sims; Rachel E J Besser; Colin Dayan; Cristy Geno Rasmussen; Carla Greenbaum; Kurt J Griffin; William Hagopian; Mikael Knip; Anna E Long; Frank Martin; Chantal Mathieu; Marian Rewers; Andrea K Steck; John M Wentworth; Stephen S Rich; Olga Kordonouri; Anette-Gabriele Ziegler; Kevan C Herold Journal: Diabetes Date: 2022-04-01 Impact factor: 9.337