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BOSTON: A groundbreaking study led by researchers at Massachusetts General Hospital (MGH) and the Broad Institute has identified numerous genetic clusters that may help explain the diverse clinical presentations of type 2 diabetes. Published in Nature Medicine, the research analyzed genetic data from over 1.4 million individuals across various ancestral backgrounds and uncovered key biological processes that likely contribute to the development of the disease.
Type 2 diabetes, a condition characterized by elevated blood sugar levels, affects approximately one in 10 people in the United States and can lead to severe health complications. Despite its prevalence, the reasons behind the variation in clinical features among individuals with the disease remain largely unknown.
“Understanding why certain people develop type 2 diabetes and why there is significant variation in clinical features is crucial,” says senior author Miriam S. Udler, MD, PhD, director of the MGH Diabetes Genetics Clinic and assistant professor of Medicine at Harvard Medical School. “Our findings provide new insights into the biology of type 2 diabetes and highlight the importance of considering genetic ancestry in disease risk and treatment.”
The study’s analyses resulted in the identification of 650 genetic variants associated with type 2 diabetes and 110 diabetes-related clinical traits. The researchers validated previously identified genetic clusters and discovered new ones related to cholesterol levels, bilirubin metabolism, and lipid processing in fat and liver tissues.
One of the key findings is that certain genetic clusters help explain differences in type 2 diabetes risk among populations. For instance, individuals from East Asian backgrounds may have a higher risk of developing the disease at lower body mass index levels due to variations in clusters related to fat usage and storage.
“Our study highlights the genetic underpinnings of type 2 diabetes and their role in explaining clinical differences across populations,” says co-lead author Kirk Smith, MS, a computational biologist in MGH’s Center for Genomic Medicine. “The genetic mechanisms we’ve identified offer the potential to guide the development of curative therapies,” adds co-lead author Aaron J. Deutsch, MD, an instructor in the division of Endocrinology at MGH.
The research was supported by the National Institute of Diabetes and Digestive and Kidney Diseases, the Doris Duke Foundation, the American Diabetes Association, and the Novo Nordisk Foundation. The findings pave the way for personalized treatment approaches that tailor therapies to individual patients’ genetic profiles, potentially revolutionizing the management of type 2 diabetes.
Resources: Brandon Chase, Massachusetts General Hospital