Life table analysis of the risk of type 1 (insulin-dependent) diabetes mellitus in siblings according to islet cell antibodies and HLA markers. An 8-year prospective study

Diabetologia. 1992 Oct;35(10):951-7. doi: 10.1007/BF00401424.

Abstract

To determine whether genetic markers can improve the predictive value of islet cell antibodies for development of Type 1 (insulin-dependent) diabetes mellitus, 536 siblings aged 2-29 years were consecutively enrolled in a 8-year prospective survey. The risk of developing diabetes was estimated, using life-table methods, by years of follow-up and age, according to genetic factors (shared HLA-haplotypes, DR antigens, C4 allotypes) and islet cell antibody status. Fifteen siblings (2.8%) developed Type 1 diabetes during the study period (risk 4.4% after 8 years, 4% by age 22 years). DR3,4 heterozygosity identified higher risk (16% after 8 years, 12% by age 22 years, p less than 10(-5)) than HLA-identity (10% and 7%, respectively, p less than 0.01); risks for DR3 or DR4 positive and for haplo-identical siblings were low (4%, 3% and 4.4%, respectively, NS). C4BQO also conferred significant risk (11% vs 3% in non-C4BQO siblings, p less than 0.01). The predictive value of genetic markers alone was poor (12% for DR3,4, 7% for HLA-identity, 9% for C4BQO) compared with that of islet cell antibody levels greater than 4 Juvenile Diabetes Foundation units (41%, risk 56% after 8 years, p less than 10(-7)). HLA markers significantly contributed to risk prediction in combination with islet cell antibodies: islet cell antibody-positive DR3,4+ subjects had the highest risk (70% after 8 years, predictive value 58%, p less than 10(-7)) compared with islet cell antibody-positive DR3,4- (37% and 20%, respectively) and islet cell antibody-negative DR3,4+ (5% and 3.6%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Autoantibodies / analysis*
  • Autoantibodies / genetics
  • Autoantibodies / immunology
  • Biomarkers / analysis
  • Child
  • Child, Preschool
  • Complement C4b / analysis
  • Complement C4b / genetics
  • Diabetes Mellitus, Type 1 / epidemiology*
  • Diabetes Mellitus, Type 1 / genetics*
  • Diabetes Mellitus, Type 1 / immunology*
  • Female
  • France / epidemiology
  • HLA Antigens / analysis*
  • HLA Antigens / genetics
  • HLA Antigens / immunology
  • HLA-DR3 Antigen / analysis
  • HLA-DR3 Antigen / genetics
  • HLA-DR4 Antigen / analysis
  • HLA-DR4 Antigen / genetics
  • Haplotypes
  • Heterozygote
  • Humans
  • Islets of Langerhans / immunology
  • Life Tables*
  • Male
  • Predictive Value of Tests
  • Prospective Studies
  • Risk Factors
  • Sibling Relations*

Substances

  • Autoantibodies
  • Biomarkers
  • HLA Antigens
  • HLA-DR3 Antigen
  • HLA-DR4 Antigen
  • islet cell antibody
  • Complement C4b