Genetic Screening for the Risk of Type 2 Diabetes

Abstract

The prevalence and incidence of type 2 diabetes, representing >90% of all cases of diabetes, are increasing rapidly throughout the world. The International Diabetes Federation has estimated that the number of people with diabetes is expected to rise from 366 million in 2011 to 552 million by 2030 if no urgent action is taken. Furthermore, as many as 183 million people are unaware that they have diabetes (www.idf.org). Therefore, the identification of individuals at high risk of developing diabetes is of great importance and interest for investigators and health care providers. Type 2 diabetes is a complex disorder resulting from an interaction between genes and environment. Several risk factors for type 2 diabetes have been identified, including age, sex, obesity and central obesity, low physical activity, smoking, diet including low amount of fiber and high amount of saturated fat, ethnicity, family history, history of gestational diabetes mellitus, history of the nondiabetic elevation of fasting or 2-h glucose, elevated blood pressure, dyslipidemia, and different drug treatments (diuretics, unselected β-blockers, etc.) (1–3). There is also ample evidence that type 2 diabetes has a strong genetic basis. The concordance of type 2 diabetes in monozygotic twins is ~70% compared with 20–30% in dizygotic twins (4). The lifetime risk of developing the disease is ~40% in offspring of one parent with type 2 diabetes, greater if the mother is affected (5), and approaching 70% if both parents have diabetes. In prospective studies, we have demonstrated that first-degree family history is associated with twofold increased risk of future type 2 diabetes (1,6). The challenge has been to find genetic markers that explain the excess risk associated with family history of diabetes. Advances in genotyping technology during the last 5 years have facilitated rapid progress in large-scale genetic studies. Since 2007, …