Type 1 Diabetes

The metabolic syndrome of type 1 diabetes results from insulin deficiency secondary to pancreatic β-cell destruction and is classified as type 1A or 1B depending on the presence or absence of pancreatic islet autoantibodies. Type 1A is an autoimmune disease in which islet autoantibodies are present by 3 years of age in the majority of children who will develop clinical disease. Susceptibility is polygenic, but alleles at the human leukocyte antigen (HLA) locus account for about half the lifetime risk. The second most significant locus is the insulin gene itself, and insulin is a key autoantigen that drives β−cell destruction. The incidence of type 1A is rising as a result of environmental factors, which has enhanced the penetrance of lower risk HLA alleles. The type 1A stereotype of the thin juvenile now overlaps with the type 2 diabetes stereotype of the obese, insulin-resistant adult. The gut microbiome, a bellwether of the external environment, is altered in type 1A and its modification may be an approach to primary prevention. Recognition that type 1A is primarily an autoimmune β-cell disease that progresses to a metabolic disorder only in its end-stage will expand therapeutic options for earlier intervention and secondary prevention.