Metabolomics Makes a Mark: Early Changes Associated With Autoimmune Diabetes

Abstract

History, to the Roman Cicero, is “the witness of time, the life of memory, the mistress of life.” But history can be a cruel mistress, illustrating all we have not achieved. A glance back challenges us to reconsider what we have learned about type 1 diabetes and to what effect. More specifically, what happened after 1974, the annus mirabilis , when The Lancet reported the genetic basis of this disease (through HLA genes) (1) and a principle disease-associated biomarker (islet cell autoantibodies) (2). Certainly, we can predict the disease broadly based on these two observations, allied to progressive loss of insulin secretion, but without any tangible clinical benenfit. For the purpose of prediction is prevention, and that, thus far, we cannot do. As a result, attention has focused on nongenetic, specifically environmental, factors that lead to type 1 diabetes and might be modified. Two features of such environmental effects have had an impact on our understanding of the disease pathogenesis, as illustrated in this month’s Diabetes (3). First, early environmental events appear to cause type 1 diabetes (4). Second, the age at diagnosis of this disease impacts the clinical phenotype (5). Twin, migration, population, and birth cohort studies emphasize the importance of environmental factors operating in early childhood when disease-predictive autoantibodies appear (6). Even disproportionate maternal and birth-related events can influence the disease risk (Table 1). Other putative factors include temperate climate, increased hygiene, increasing wealth, overcrowding in childhood, virus infections, early diet including exposure to cow’s milk, reduced rates or duration …