Age and number of islet autoantibodies associated with diabetes risk

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1. Patients with a younger age of autoantibody seroconversion were associated with an increased risk of developing type 1 diabetes.

2. Patients with a higher numbers of islet autoantibodies were associated with an increased risk of developing type 1 diabetes.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Type 1 diabetes is usually seen in young individuals who have developed autoantibodies to their pancreatic islet B cells, which normally function to secrete insulin. The initial manifestation of type 1 diabetes may be the asymptomatic seroconversion of such autoantibodies. Eventually, beta-cell function continues to decline over years until glucose and C-peptide concentrations meet diagnostic criteria for type 1 diabetes. In this study, the authors perform a meta-analysis of three prospective cohort studies from Colorado, Finland, and Germany to evaluate the disease course of diabetes in children known to be at a genetic risk.

Out of 585 children who developed 2 or more pancreatic autoantibodies, 69.7% developed diabetes within 10 years and 84.2% developed it within 15 years. The results of this analysis are particularly strengthened with the utilization of 3 study centers across different countries that provide similar results. Nonetheless, it should be noted that the entry criteria were not standardized between the 3 studies which may affect the analysis. Moving forward, the present study raises the need to further investigate interventions that could reduce one’s risk of type 1 diabetes or delay its onset.

Click to read the study, published today in JAMA

Click to read an accompanying editorial, published today in JAMA

Relevant Reading: Genetic, pathogenesis and clinical interventions in type 1 diabetes.

In Depth [meta-analysis]: This meta analysis examined 13,377 children enrolled into prospective studies in Colorado (n=1,962) Finland (n=8,597), and Germany (n=2,818). A total of 1,059 children seroconverted to islet autoantibody-positive while 12,318 remained islet autoantibody-negative. In total, 428 children developed diabetes (403 autoantibody-positive and 25 autoantibody- negative). 585 (4.4%) of the 1059 developed multiple islet autoantibodies. The median age of seroconversion in these 585 children was 2.1 years. A total of 355 children (60.7%) with multiple islet autoantibodies progressed to diabetes at a median of 3.5 years post-seroconversion. Following seroconversion of multiple autoantibodies, 43.5% (95% CI, 39.4%-47.8%) developed diabetes within 5 years and 69.7 (95%CI, 65.1%-74.3%) percent developed diabetes by within 10 years. An age <3 years at seroconversion was associated with a quicker onset of diabetes.

By John Prendergass and Rif Rahman

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