Article

Diabetologia

, Volume 45, Issue 6, pp 798-804

First online:

Permanent diabetes mellitus in the first year of life

  • D. IafuscoAffiliated withDepartment of Paediatrics, Second University of Naples, Via S. Andrea delle Dame n 4 – 80100 Napoli
  • , M. StaziAffiliated withDepartment of Epidemiology – Istituto Superiore di Sanità, Rome
  • , R. CotichiniAffiliated withDepartment of Epidemiology – Istituto Superiore di Sanità, Rome
  • , M. CotellessaAffiliated withDepartment of Paediatrics, University of Genoa, G. Gaslini Institute, Genoa
  • , M. MartinucciAffiliated withRegional Center for Juvenile Diabetes, Meyer Paediatric Hospital, Florence
  • , M. MazzellaAffiliated withDepartment of Paediatrics, University of Genoa, G. Gaslini Institute, Genoa
  • , V. CherubiniAffiliated withDepartment of Paediatrics, University of Ancona, Ancona
  • , F. BarbettiAffiliated withLaboratory of Molecular Endocrinology and Metabolism, IBCIT, Biomedical Scientific Park Rome S. Raffaele, Rome and Bambino Gesù Paediatric Hospital, IRCCS, Rome
  • , M. MartinettiAffiliated withHLA Laboratory, Immunohematology and Transfusion Center, IRCCS Policlinic, Pavia
    • , F. CeruttiAffiliated withDepartment of Paediatrics, University of Turin, Turin
    • , F. PriscoAffiliated withDepartment of Paediatrics, Second University of Naples, Via S. Andrea delle Dame n 4 – 80100 Napoli
    • , and the Early Onset Diabetes Study Group of the Italian Society of Paediatric Endocrinology and Diabetology Affiliated withDepartment of Paediatrics, Second University of Naples, Via S. Andrea delle Dame n 4 – 80100 Napoli

Abstract

Aims/hypothesis. The pathogenesis of permanent diabetes mellitus diagnosed early in life is heterogeneous and, in most cases, not known. We aimed at identifying markers differentiating between non-autoimmune and autoimmune diabetes.

Methods. The clinical, genetic and epidemiological features of 111 diabetic patients (62 males) who received insulin within 12 months of life were studied.

Results. The epidemic curve by age of diabetes onset revealed two subsets of patients at a cutoff of 180 days. In the group with diabetes onset before 180 days ("early onset" permanent diabetes) the analysis of HLA susceptibility heterodimers (available for 21 individuals) showed that 76% had a "protective" HLA genotype for Type I (insulin-dependent) diabetes mellitus as compared to 11.9% (5/42) of the later onset group. Accordingly, "early onset" children were less likely to have autoimmunity markers (4 out of 26 tested) than children with onset after 180 days (13 out 20 tested) (15.4% vs. 65.0%, p<0.01). Of note, 19 out of 20 (or the 95%) patients who were born on the island of Sardinia, an Italian region where the incidence of Type I diabetes is six times higher than continental Italy (33/100000/year vs 5/100000/year), were included in the later onset group (>180 days). Small-for-date birthweight, a possible sign of reduced foetal insulin secretion, was more common in the "early onset" group (OR=9.9, 95%-CI 2.6–38.6).

Conclusion/interpretation. These results, obtained in the largest population-based cohort of diabetic infants hitherto reported, suggest that "early onset" permanent diabetes cases differ from later onset cases and that most of them do not have an autoimmune pathogenesis.

Permanent neonatal diabetes non-autoimmune diabetes mellitus Type I diabetes HLA protective heterodimers autoimmune enteropathy