Diabetes is a disease of dys-regulation of glucose and lipid homeostasis that does not only affect the insulin production in the β cells but also the metabolism in organs such as liver, muscle and fat. Worldwide, the prevalence of T2D is rapidly increasing, which, when not properly treated, ultimately leads to reduced life expectancy due to microvascular (retinopathy, nephropathy and neuropathy) and macrovascular (heart disease and stroke (Chap. 11) complications. Like in obesity (Chap. 8), both genetic and environmental factors contribute to the development of diabetes. For example, persons at high risk for developing T2D should benefit from lifestyle changes involving healthy diet, moderate weight loss and increased physical activity. Despite large GWAS screening for risk genes, at present less than 10 % of the inheritance of T2D is understood. Therefore, in addition, epigenome-wide changes, both pre-natal as well as in adult life, are intensively investigated.
In this chapter, we will describe the different forms of diabetes, their diagnosis and the worldwide prevalence of the disease. We will discuss the dys-regulation of glucose homeostasis in T2D. In this context, we will present the genetic and physiologic basis of the disease and again we will highlight chronic inflammation as the core of the disease, this time affecting islets of the pancreas. We will realize that the present understanding of T2D risk genes is insufficient and that most likely epigenetics plays an important role in the disease, as examplified through the thrifty gene hypothesis.
KeywordsT1D T2D OGTT Insulin β cells Liver Skeletal muscle Adipose tissue Inflammation MODY GWAS Epigenetic programming Thrifty gene hypothesis
- International Diabetes Federation (IDF): www.idf.org/diabetesatlas