Dissection of type 2 diabetes: a genetic perspective

Abstract

Diabetes is a leading cause of global mortality and disability, and its economic burden is substantial. This Review focuses on type 2 diabetes, which makes up 90-95% of all diabetes cases. Type 2 diabetes involves a progressive loss of insulin secretion often alongside insulin resistance and metabolic syndrome. Although obesity and a sedentary lifestyle are considerable contributors, research over the last 25 years has shown that type 2 diabetes develops on a predisposing genetic background, with family and twin studies indicating considerable heritability (ie, 31-72%). This Review explores type 2 diabetes from a genetic perspective, highlighting insights into its pathophysiology and the implications for precision medicine. More specifically, the traditional understanding of type 2 diabetes genetics has focused on a dichotomy between monogenic and polygenic forms. However, emerging evidence suggests a continuum that includes monogenic, oligogenic, and polygenic contributions, revealing their complementary roles in type 2 diabetes pathophysiology. Recent genetic studies provide deeper insights into disease mechanisms and pave the way for precision medicine approaches that could transform type 2 diabetes management. Additionally, the effect of environmental factors on type 2 diabetes, particularly from epigenetic modifications, adds another layer of complexity to understanding and addressing this multifaceted disease.