Familial clustering of diabetic kidney disease and retinopathy in offspring of parents with type 1 diabetes: a population-based study.

Isabella Herrlin; Fanny Jansson Sigfrids; Niina Sandholm; Lena M Thorn; Per-Henrik Groop; Valma Harjutsalo
Abstract
Familial clustering of diabetic kidney disease and diabetic retinopathy has been reported among siblings with type 1 diabetes. We aimed to further unveil the phenomenon among parent-offspring pairs. Among all individuals diagnosed with type 1 diabetes between 1965 and 1979 in Finland (n = 5144) with at least one child with the same disease and a diabetes duration of 15 years or more, we compiled a population-based study cohort comprising 221 parent-offspring pairs. The original cohort was compiled by the Finnish Institute for Health and Welfare, and their offspring identified from the Finnish Central Population Register. The status of diabetic kidney disease and severe diabetic retinopathy (defined as retinal laser treatment) was determined by systematically reviewing the participants' medical records. The follow-up ranged from the diabetes onset until 31 December 2020. In total, 56 (32%) parents developed severe albuminuria and 84 (51%) severe diabetic retinopathy during follow-up. Among the offspring of parents free of kidney disease, 23 (18%) developed moderate albuminuria, 10 (8%) developed severe albuminuria, and 1 (1%) developed kidney failure, while among offspring of parents with kidney disease, 20 (34%) developed moderate albuminuria, 10 (17%) developed severe albuminuria, and 1 (2%) developed kidney failure during follow-up. Among the offspring of parents free of severe diabetic retinopathy, 8 (9%) developed severe diabetic retinopathy, whereas the corresponding proportion was 29 (33%) among the offspring of parents with severe diabetic retinopathy. The presence of severe albuminuria in the parent increased the risk of offspring moderate albuminuria 2.27-fold (95% confidence interval 1.25-4.14, p = 0.0075) and offspring severe albuminuria 2.41-fold (1.00-5.83, p = 0.049), as compared to offspring of parents without kidney disease. The presence of kidney failure in the parent further increased the risk of offspring moderate albuminuria to 2.60-fold (1.33-5.07, p = 0.0051) and offspring severe albuminuria to 3.04-fold (1.21-7.65, p = 0.019). Severe diabetic retinopathy in the parent increased the risk of the same complication in the offspring 4.34-fold (1.98-9.50, p = 0.00024). Offspring of parents with diabetic kidney disease or severe diabetic retinopathy have a several-fold risk of developing the corresponding complication compared with offspring of parents without the complications. This observation highlights the importance of family history when assessing the complication risk among individuals with type 1 diabetes. Folkhälsan Research Foundation, Medical Society of Finland, Wilhelm and Else Stockmann Foundation, Finnish Diabetes Research Foundation, Waldemar von Frenckell Foundation, Liv och Hälsa Society, Academy of Finland (grant number 316664), Novo Nordisk Foundation (grant number NNF OC0013659).
Journal ECLINICALMEDICINE
ISSN 2589-5370
Published 01 May 2025
Volume 83
Issue
Pages 103232
DOI 10.1016/j.eclinm.2025.103232
Type Journal Article
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