Type 1 diabetes risk assessment : improvement by follow-up measurements in young islet autoantibody-positive relatives

• Published in: Diabetologia 2006-12, Vol.49 (12), p.2969-2976
• Main Authors: ACHENBACH, P, WARNCKE, K, REITER, J, WILLIAMS, A. J. K, ZIEGLER, A. G, BINGLEY, P. J, BONIFACIO, E
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Algorithms; Antibodies; Autoantibodies - blood; Biological and medical sciences; Child; Child, Preschool; Diabetes; Diabetes Mellitus, Type 1 - epidemiology; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 1 - mortality; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Families & family life; Family; Follow-Up Studies; Humans; Insulin; Islets of Langerhans - immunology; Medical sciences; Middle Aged; Models, Genetic; Proportional Hazards Models; Proteins; Risk Assessment; Survival Analysis; Time Factors
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s00125-006-0451-9

Combinations of autoantibody characteristics, including antibody number, titre, subclass and epitope have been shown to stratify type 1 diabetes risk in islet autoantibody-positive relatives. The aim of this study was to determine whether autoantibody characteristics change over time, the nature of such changes, and their implications for the development of diabetes. Five-hundred and thirteen follow-up samples from 141 islet autoantibody-positive first-degree relatives were tested for islet autoantibody titre, IgG subclass, and GAD and IA-2 antibody epitope. All samples were categorised according to four risk stratification models. Relatives had a median follow-up of 6.8 years and 48 developed diabetes during follow-up. Survival analysis was used to determine the probability of change in risk category and of progression to diabetes. For each stratification model, the majority of relatives (71-81%) remained in the same risk category throughout follow-up. In the remainder, changes occurred both from lower to higher and from higher to lower risk categories. For all four models, relatives aged < 15 years were more likely to change risk category than those aged >15 years (0.001 < p < 0.03). Relatives whose autoantibody status changed from low- to high-risk categories had a higher risk of diabetes than relatives who remained in low-risk categories, and inclusion of autoantibody status during follow-up improved diabetes risk stratification in Cox proportional hazards models (p < 0.001). Changes in islet autoantibodies are relevant to pathogenesis, and are likely to signal alterations in the disease process. Detection of changes through follow-up measurement will improve diabetes risk stratification, particularly in young individuals.