Understanding the Pathogenesis, Therapeutic Targets/Drug Action and Pharmacogenetics of Type 2 Diabetes: Is there a Future for Personalised Medicine?

Abstract

Type 2 diabetes (T2D) is a chronic non-communicable disease that is of major health concern with a steadily rising prevalence across the globe. It is a metabolic disorder characterized by high blood glucose level either as a result of impaired insulin secretion and/or insulin action usually termed insulin resistance. This disease is influenced by lifestyle/feeding habit changes and genetic factors that cause physiological changes in glucose and lipid metabolism. As such, antidiabetic treatments have targeted specific enzymes, receptors, transport proteins, hormones, transcription factors, etc. that are related to glucose metabolism, fat metabolism, insulin secretion and insulin signalization. Genetic variations due to mutations in certain target genes have been shown to influence the pathogenesis of T2D but also these polymorphisms have been observed to alter the therapeutic efficacy of drugs as well as their safety. Pharmacogenetic studies have been able to identify specific genetic variants of target genes that affect the metabolism, therapeutic response and adverse effects of antidiabetic drugs with the aim to translate the research findings to clinical practice. However, pharmacogenetic studies have not fully been able to identify distinct genetic markers that can serve as biomarkers for genetic screening, thus, limiting personalised medicine. As we advocate personalised medicine for the management of T2D in the future, pharmacogenetic studies should lay emphasis on addressing challenges of genetic screening and its translation to personalised therapy.