Summary
The possible association between residual B-cell function and specific HLA antigens in Type 1 (insulin-dependent) diabetes was studied in a cross-sectional series of 144 diabetic children and adolescents, as well as in a prospective series of 44 newly diagnosed diabetic subjects who were observed for the initial 2 years of their diabetes. In the cross-sectional study, the HLA-Dw3/Dw4 heterozygotes had a lower mean serum C-peptide concentration during 1980, 0.03 ±0.01 nmol/l (mean ± SEM) vs. 0.09 ± 0.01 nmol/1 (p < 0.02), as well as a lower 24-h urinary C-peptide excretion, 0.27 ±0.06 nmol/m2 vs. 1.34 ± 0.19 nmol/m2 (p < 0.05), than the other subjects. In addition, the Dw3/Dw4 heterozygotes had a clinical remission of shorter duration, 113 ± 47 days vs. 203 ± 22 days (p < 0.05), and a higher mean glycosylated haemoglobin level during 1980, 14.8 ± 0.05% vs. 13.7 ± 0.2% (p < 0.05), than those without the Dw3/Dw4 combination. In the prospective study the serum C-peptide concentrations were of the same magnitude in the Dw3/Dw4 heterozygotes and the other subjects during the first month. Subsequently the C-peptide concentrations in the subjects with the Dw3/Dw4 combination started to decrease 2 months earlier than in the other subjects. The Dw3/Dw4 children had a significantly lower serum C-peptide concentration at 21 months, 0.01 ± 0.01 nmol/1 vs. 0.13 ± 0.02 nmol/1 (p<0.01), and at 24 months, 0.03 ±0.01 nmol/1 vs. 0.12 ± 0.02 nmol/l (p < 0.05). Our observations suggest that Dw3/Dw4 heterozygosity is, at least in children, associated with a distinct form of Type 1 diabetes characterized by a rapid B-cell destruction, a clinical remission of short duration and poor metabolic control. This expands the concept of genetic heterogeneity within Type 1 diabetes in childhood, and may have important implications for research on the aetiology, pathogenesis and natural history of the disease.
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Knip, M., Ilonen, J., Mustonen, A. et al. Evidence of an accelerated B-cell destruction in HLA-Dw3/Dw4 heterozygous children with Type 1 (insulin-dependent) diabetes. Diabetologia 29, 347–351 (1986). https://doi.org/10.1007/BF00903342
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DOI: https://doi.org/10.1007/BF00903342