Type 1 diabetes disease characteristics differ based on age at diagnosis

Issue: October 2011

EASD 47th Annual Meeting

LISBON — A new study reported differing characteristics of type 1 diabetes among different age groups of children.

“If children diagnosed under the age of 15 years are grouped into age categories there are definitely differences in the disease characteristics between the groups,” Mikael Knip, MD, PhD, of the Children’s Hospital at University of Helsinki and Helsinki University Central Hospital, Finland, said in a press release.

According to Knip, based on data from the Childhood Diabetes in Finland (DiMe) study, children who were diagnosed with type 1 diabetes at age 2 years or younger were characterized by higher plasma glucose, higher acidity, higher frequency of diabetic ketoacidosis and lower serum C-peptide concentrations at diagnosis. In addition, the younger children tested positive for insulin autoantibodies more frequently, and had higher titers of islet cell antibodies and insulin autoantibodies. The islet antigen 2 antibody (IA-2A) levels tended to be lower in this group, and the children also carried protective HLA genotypes less often than older children, according to information from the press release.

Knip also discussed data based on children from the Finnish Pediatric Diabetes Register and Biobank who were diagnosed at age 15 years or younger. The children were analyzed in three age groups: diagnosis before age 5 years; diagnosis at 5 to 9.9 years; and diagnosis at 10 to 14.9 years. Those diagnosed at the youngest ages were characterized by higher frequency and higher titers of insulin autoantibodies, and lower frequency and lower titers of IA-2A and antibodies to zinc transporter 8 (ZnT8A). The oldest age group had higher plasma glucose and lower pH at diagnosis than the middle age group, and a higher frequency of diabetic ketoacidosis. Older age at diagnosis was also associated with lower frequencies and titers of islet cell antibodies, insulin autoantibodies, IA-2A and ZnT8A when compared with children who were diagnosed at age 5 to 9.9 years. In contrast, GADA titers were higher in the oldest age group.

Knip said these data suggest that the type 1 diabetes disease process is more aggressive in younger children, leading to a more rapid progression to overt disease.

The HLA genes on the short arm of chromosome 6 confer about half of the genetic susceptibility to type 1 diabetes; more than 40 non-HLA polymorphisms contribute to the remaining half. Knip and colleagues studied possible heterogeneity related to age at diagnosis in the risk associations of 23 non-HLA genes with type 1 diabetes. Four of the genetic polymorphisms were associated with an increased risk among children diagnosed younger than 5 years (odds ratio ranged from 1.44 to 1.60); no significant increased risk was found among older children.

“Taken together, there seems to be clinical, immunological and genetic heterogeneity of type 1 diabetes presenting in childhood,” Knip stated in the release. “Whether such heterogeneity should be reflected in the treatment and care of children affected by type 1 diabetes remains to be defined.”

He suggested that future clinical trial participants be genotyped in more detail to assess whether the new therapy may be more effective among carriers of specific genotypes. — by Katie Kalvaitis

For more information:

Knip M. Diabetes in young people. Is childhood type 1 diabetes a homogeneous condition? Presented at: The European Association for the Study of Diabetes 47th Annual Meeting; Sept. 12-16, 2011; Lisbon.

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