CAMBRIDGE, England—Researchers have discovered 13 new genetic variants that influence blood glucose regulation, insulin resistance and the function of insulin-secreting beta cells in populations of European descent; five of the newly discovered variants increase the risk of developing type 2 diabetes.
The studies appear online Jan. 17, 2010, in Nature Genetics and reveal clues about the role of beta cells in the development of type 2 diabetes.
Both studies were conducted by the Meta-Analyses of Glucose and Insulin-related Traits Consortium (MAGIC), a collaboration among researchers from centers in the United States, Canada, Europe and Australia that analyzed gene samples from 54 previous studies involving more than 122,000 individuals of European descent. The study, co-led by MGH scientists along with colleagues from Boston University, University of Cambridge, University of Oxford and the University of Michigan, began by analyzing about 2.5 million gene variations (called SNPs) from 21 genome-wide searches for variants associated with glucose and insulin regulation in more than 46,000 non-diabetic participants. The 25 most promising SNPs from the first phase were then tested in more than 76,000 non-diabetic participants in 33 other studies, leading to new associations of nine SNPs with fasting glucose levels and one with fasting insulin and with a measure of insulin resistance.
Analysis of genetic data from additional studies involving both diabetic and non-diabetic participants found that five glucose-level-associated variants—two of those newly identified and three discovered in previous studies—were also shown to raise type 2 diabetes risk. Most of the diabetes-associated variants appear to act through their impact on insulin secretion by the pancreatic beta cells and not by insulin resistance, which suggests, the authors note, that environmental factors such as diet, lifestyle and obesity may play a larger role in insulin resistance than in insulin secretion.
