Endocrine Abstracts

Worldwide diabetes epidemic leads to exponential increase in incidence and prevalence of associated co-morbidities and mortality. During the last 10 years we have devoted to investigate how clinical and genetic biomarkers can be used to facilitate prediction of these life-threatening hazards. Accumulating evidence from our large prospective studies indicate that decline in insulin secretion adjusted for the degree of insulin sensitivity is the key factor contributing to overt type 2 diabetes. Furthermore, genetic data indicate that risk alleles in genetic loci for type 2 diabetes influenced changes in pancreatic beta-cell function over time, while having no effect on changes in body mass index. Presently, genetic information has insufficient power to predict common type 2 diabetes. However, our follow-up studies on variants in TCF7L2, MTNR1B, GIPR, GRB10 genes unravelled multiple and pleiotropic mechanisms of genetic loci which significantly contributed to our understanding of pathogenesis of type 2 diabetes including effects on insular-incretin axis (GIP/GLP-1 and glucagon) and hepatic glucose production in the liver. We and others have also reported α-hydroxybutyrate, linoleoyl glycerophosphocholine, and copeptin as novel biomarkers to be associated with increased risk of type 2 diabetes. However, these new biomarkers require a systematic evaluation and validation across different studies and populations before their actual diagnostic and prognostic value is confirmed.