Affected brother as the highest risk factor of type 1 diabetes development in children and adolescents: One center data before implementing type 1 diabetes national screening

Anna Wędrychowicz; Teresa Grzelak; Alicja Pietraszek; Maria Skrzyszowska; Mari Minasjan; Jerzy B Starzyk

doi:10.17219/acem/172446

Affected brother as the highest risk factor of type 1 diabetes development in children and adolescents: One center data before implementing type 1 diabetes national screening

Adv Clin Exp Med. 2023 Nov 24. doi: 10.17219/acem/172446. Online ahead of print.

Authors

Anna Wędrychowicz^{1

2}, Teresa Grzelak³, Alicja Pietraszek⁴, Maria Skrzyszowska⁴, Mari Minasjan⁴, Jerzy B Starzyk^{1

2}

Affiliations

¹ Department of Pediatric and Adolescent Endocrinology, Pediatric Institute, Jagiellonian University Medical College, Kraków, Poland.
² Department of Pediatric and Adolescent Endocrinology, University Children's Hospital, Kraków, Poland.
³ Department of Physiology, Poznan University of Medical Sciences, Poland.
⁴ Students' Scientific Society at the Department of Pediatric and Adolescent Endocrinology, Pediatric Institute, Jagiellonian University Medical College, Kraków, Poland.

PMID: 37999638
DOI: 10.17219/acem/172446

Abstract

Background: There is an increased risk for childhood type 1 diabetes (T1D) when T1D and type 2 diabetes (T2D) are reported in relatives.

Objectives: Our objective was to evaluate current family risk factors for T1D development before implementing a national screening program for T1D.

Material and methods: A population of 879 Caucasian children and adolescents with T1D and 286 healthy controls were enrolled in the study. All participants completed the same questionnaire, which collected information about family history of diabetes over 3 generations. In statistical analyses, frequency tables and χ2 tests evaluated possible multicollinearity among risk factors that were significantly associated with the outcomes.

Results: Family history of diabetes was more frequent in controls (n = 75, 26.2%) than in patients with T1D (n = 146, 16.6%, odds ratio (OR) = 1.785, 95% confidence interval (95% CI): 1.299-2.452, degrees of freedom (df) = 12.976, p = 0.004), especially with a family history of T2D (n = 62, 21.7% compared to n = 79, 9.0%, respectively, OR = 2.803, 95% CI: 1.948-4.034, df = 32.669, p < 0.001). Also, there was a tendency for the nuclear family of T1D patients to be more frequently affected by T1D (n = 74, 8.4%) than the controls (n = 15, 5.2%, OR = 1.605, 95% CI: 0.937-2.751, df = 3.081, p = 0.079). The risk of T1D was associated with the closest family members being affected and accelerated over generations. Indeed, it was highest in siblings, especially brothers (OR = 12.985, 95% CI: 0.782-215.743, Fisher's test: p < 0.001). A positive family history of T2D burden among second-degree relatives was 2.728 times more frequent in the control group than in the T1D group (OR = 2.728; 95% Cl: 1.880-3.962, p < 0.001). Furthermore, a positive family history of T1D among first-degree relatives was less frequent in the controls than in the T1D group (OR = 0.124; 95% Cl: 0.030-0.516, p = 0.004).

Conclusions: A family history of T1D, but not T2D, is a significant risk factor for T1D development. Indeed, the priority in screening for T1D should be given to first-degree relatives of T1D patients, starting from siblings.

Keywords: family history of diabetes; first-degree relatives; siblings; type 1 diabetes mellitus; type 2 diabetes mellitus.