ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2021) 18 10.13 | DOI: 10.1530/ey.18.10.13

Diabetologia. 2020;63(12):2605–2615. doi: 10.1007/s00125-020-05276-4.

Diabetes diagnosed at <6 months of age is often of monogenic origin. However, 10-15% of affected infants do not have a pathogenic variant in one of the 26 known neonatal diabetes genes. In this study, 166 infants diagnosed at <6 months of age without such pathogenic variants showed all the the classic features of T1D.

They were compared to infants with monogenic neonatal diabetes (n=164) and children with T1D diagnosed at age 6–24 months (n=152). T1D genetic risk score (T1D-GRS), islet autoantibodies, C-peptide and clinical features were assessed and recorded.

An excess of infants with high T1D-GRS was found: 38% (63/166) had a T1D-GRS >95th centile of healthy individuals (5% would be expected by chance). Infants with a high T1D-GRS had a similar rate of autoantibody positivity to infants with T1D diagnosed at age 6–24 months (41% vs 58%, P=0.2), and had markedly reduced C-peptide levels (median <3 pmol/l within 1 year of diagnosis), indicating rapid loss of insulin secretion. These infants also had reduced birthweights (median z score −0.89), especially among infants diagnosed with T1D at <3 months (median z score −1.98).

Comprehensive genetic testing for all neonatal diabetes genes remains essential for all infants diagnosed with diabetes at <6 months of age. However, these findings provide strong evidence that T1D can present even before age 6 months. These infants show the classic features of T1D: high polygenic genetic risk, autoimmunity and rapid beta cell loss. Furthermore, the association with reduced birthweight raises the possibility of reduced insulin secretion already in utero. This population may represent a subgroup of patients with a high potential for early comorbidities and related disease.

Article tools

My recent searches

No recent searches.