ESPE Yearbook of Paediatric Endocrinology

To read the full abstract: Diabetes Care. 2018;41:311-317

Some researchers assume that the etiology of T1DM is distinct from that of Type 2 diabetes mellitus. T1DM is characterized by autoimmune phenomena leading to the destruction of pancreatic islets and most importantly of beta-cells. Genetic factors are thought to influence the likelihood of autoimmune phenomena developing into overt autoimmune disease. Type 2 diabetes on the other hand is characterized by genetic susceptibility and mainly obesity traits leading to an exhaustion of the pancreatic insulin-synthesizing cell populations and insulin resistance in adipose tissue and other organs. Both, the exhaustion of the insulin synthesizing capacity on the one hand side and insulin resistance and glucose intolerance on the other hand can occur in different stages of both T1DM and Type 2 diabetes.

Here, the group from the Baylor College, Houston, Texas, investigated TCF7L2 gene variants in more than 800 patients with T1DM. TCF7L2 is thought to play a role in Type 2 diabetes and namely the development of insulin resistance even at a young age. Surprisingly, and unexpectantly Type 2 diabetes-linked TCF7L2 variants were associated with single autoantibody (among those ≥12 years old), higher C-peptide AUC, and lower glucose AUC levels during an OGTT at new-onset T1DM. The authors conclude that carriers of the TCF7L2 variant had a milder immunologic and metabolic phenotype at T1DM diagnosis. Thus, a genetic background that increases the risk to develop type 2 diabetes actually led to a milder manifestation of the autoimmune type of the disease. It is completely unclear which Type 2 diabetes-like pathogenic mechanisms may be linked to this phenomenon. In any case, this study shows that different and variable pathogenetic mechanisms cause T1DM and/or Type 2 diabetes and in the end the two disease may yet be different disease entities with common end-points namely glucose intolerance and destruction or loss of the insulin reserve.