Abstract
Recognized in 2006 as a global health priority by the United Nations, type 2 diabetes (T2D) is a major disease affecting 300 million individuals worldwide and directly responsible for at least 4 million deaths every year. About 10% of global health care spending is already related to T2D or to its complications, and this is steeply increasing, for instance in France, where diabetes costs have been growing by 9% per year in the last decade. Furthermore, as a consequence of the obesity epidemics, which affects nearly 1 billion individuals today, the number of diabetic people is expected to double in the next twenty years. It is now believed that 1 in 3 children born in the US since 2000 will develop T2D and its late complications and comorbidities during lifetime. As a consequence, for the first time in the last 200 years the life expectancy of this US generation could be shorter than that of previous ones. Similar trends are expected in other western countries. The root cause of metabolic diseases is the interaction among several genes and between these genes and the patient’s environment and lifestyle. For more than a decade much expenditure has been spent to identify disease genes that predispose to T2D and obesity. A comprehensive map of interacting disease genes would lead to an unprecedented understanding of their pathogenesis. This would lead to targets for new and better drugs to fill depleted pharma pipelines with drug candidates that directly address the root causes of the disease or to diagnostics that are predictive of the disease or drug response. The Holy Grail arising from such discoveries could result in the combination of a drug tailored to patients with a particular genetic profile and a molecular diagnostic for selecting patients with that profile. This “individualized” or “personalized” drug would have a high probability of producing an optimal response and a low probability of causing an adverse reaction. This article summarizes current strategies and experimental efforts for the identification of those drugs, including their underlying molecular targets, as well as diagnostic tools for the therapy and prediction of T2D and obesity with emphasis on energy uptake and expenditure, low-grade inflammation, lipotoxicity, lipid metabolism, white and brown adipose tissue, microvesicles, circadian clock, gut flora and somatic gene therapy. The opportunities and challenges for future personalized therapy of T2D and obesity are discussed.
Keywords: Copy number variants, exosomes, gene therapy, genome-wide associations, glimepiride, insulin, lipotoxicity, metabolic diseases, microvesicles, obesity, personalized medicine, single-nucleotide polymorphisms, type II diabetes, white and brown adipose tissue
11