What Have Slow Progressors Taught Us About T1D-Mind the Gap!

Abstract

Purpose of review: Progression rate from islet autoimmunity to clinical diabetes is unpredictable. In this review, we focus on an intriguing group of slow progressors who have high-risk islet autoantibody profiles but some remain diabetes free for decades.

Recent findings: Birth cohort studies show that islet autoimmunity presents early in life and approximately 70% of individuals with multiple islet autoantibodies develop clinical symptoms of diabetes within 10 years. Some "at risk" individuals however progress very slowly. Recent genetic studies confirm that approximately half of type 1 diabetes (T1D) is diagnosed in adulthood. This creates a conundrum; slow progressors cannot account for the number of cases diagnosed in the adult population. There is a large "gap" in our understanding of the pathogenesis of adult onset T1D and a need for longitudinal studies to determine whether there are "at risk" adults in the general population; some of whom are rapid and some slow adult progressors.

Keywords: Adult onset; Islet autoantibodies; Slow progression; Type 1 diabetes (T1D).

Fig. 1

Timeline towards focused study of type 1 diabetes in childhood populations. In the 1970s, data from pancreatic histology, the description of islet antibodies and genetic association with HLA confirmed the autoimmune basis of the condition. The observation of increased HLA mediated susceptibility in those developing the condition young, and the need for defined phenotypes for successful GWAS has resulted in excellent characterisation of early-onset diabetes but relative lack of understanding of the pathogenesis of adult onset type 1 diabetes