New insights from monogenic diabetes for “common” type 2 diabetes

Abstract

Boundaries between monogenic and complex genetic diseases are becoming increasingly blurred, as a result of better understanding of phenotypes and their genetic determinants. This had a large impact on the way complex disease genetics is now being investigated. Starting with conventional approaches like familial linkage, positional cloning and candidate genes strategies, the scope of complex disease genetics has grown exponentially with scientific and technological advances in recent times. Despite identification of multiple loci harboring common and rare variants associated with complex diseases, interpreting and evaluating their functional role has proven to be difficult. Information from monogenic diseases, especially related to the intermediate traits associated with complex diseases comes handy. The significant overlap between traits and phenotypes of monogenic diseases with related complex diseases provides a platform to understand the disease biology better. In this review, we would discuss about one such complex disease, type 2 diabetes, which shares marked similarity of intermediate traits with different forms of monogenic diabetes.

Diabetes and data in many forms

“…Resultantly, the major limitation in applying diabetes genomics to clinical care is the lack of genomic findings which can be used in clinical practice [31]. The way forward seems to consist of improved understanding of genetic variant interactions with environmental factors [32]. Given the low penetrance of most alleles in type 2 diabetes and poor predictive value, methods must be devised to communicate the risks accruing from genetic factors so that beneficial health outcomes can be achieved [33].…”

The Impact of Personalized Medicine of Type 2 Diabetes Mellitus in the Global Health Context

“…Moreover, T2DM is increasingly considered a polygenic syndrome comprising multiple phenotypic changes (insulin resistance, decrease in β-cell function) rather than a single disease. The complexity of pathways leading to T2DM is hence a further hindering factor in the way to identify one clear set of genes [30]. Insights from different types of diabetes may help to highlight the role of single genes in β-cell (dys)function in the pathogenesis of T2DM.…”

Identification of Novel Potential Type 2 Diabetes Genes Mediating β-Cell Loss and Hyperglycemia Using Positional Cloning

“…Type 2 diabetes (T2D) arises from a complex interplay of multiple genetic and environmental factors that contribute to inadequate insulin secretion, insulin resistance, or both ( American Diabetes Association, 2005 ; Tallapragada et al, 2015 ). A high percentage of obese people become diabetic, and the majority will at least experience insulin resistance and some degree of β-cell dysfunction ( Kahn et al, 2006 ).…”