Type 2 diabetes (T2D) is a major and growing health problem throughout much of the world. Its primary initial characteristic is high blood sugar, often caused by a combination of increased insulin resistance in the tissues and decreased output from the pancreatic β cells that produce insulin. Ultimately, the bcells cannot produce sufficient insulin to regulate blood sugar levels, leading to potential complications such as kidney dysfunction, eye problems, nerve damage and more. While behavioral and pharmaceutical interventions can moderate disease progression, there is no cure.
Poor diet, obesity and a sedentary lifestyle are among the important risk factors for T2D, but they are not deterministic. Most overweight, sedentary people do not develop the disease, and some thin, active people do. Genetic susceptibility, then, also plays a large role, but efforts to identify the causative factors have encountered daunting challenges. Hundreds of genomic sites have been associated with T2D—roughly 500 at last count—but none have been found to have a large effect in isolation. So how can scientists wade through the puzzle of variable environments and behaviors combined with complex genetics to reveal the biology underlying T2D and identify targets for more effective treatments?