If you knew you were genetically predisposed to developing a disease like type 2 diabetes, would you live your life differently? See a doctor regularly, try to eat better, or exercise more? And if you did get sick, what if knowledge about your genetic makeup could inform better, more personalized therapies?

Type 2 diabetes, also known as diabetes mellitus, is a chronic condition characterized by persistently high blood sugar levels, which affects hundreds of millions of people worldwide, according to the International Diabetes Federation. Uncontrolled, it can cause serious health complications over time, including heart disease, stroke, nerve damage, and kidney disease.

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Environmental and lifestyle factors, such as body mass index (BMI), diet, and exercise, are known to impact one’s risk of developing diabetes, but genes also play an important role. At UMass Amherst, researchers in the Spracklen Lab are gaining valuable new insights into the genetic epidemiology of type 2 diabetes.

“Type 2 diabetes has a huge impact on public health and quality of life,” says Cassandra Spracklen, associate professor of epidemiology in the UMass Amherst School of Public Health & Health Sciences. “We’re working to better understand the genetics of type 2 diabetes and related cardiometabolic traits—like glucose, lipids, insulin, and BMI—and, ultimately, improve prevention and treatment of this disease.” 

A Complex Puzzle of Risk Factors

Spracklen completed her graduate training in epidemiology at the University of Iowa, where her research focused on pregnancy outcomes. Near the end of her PhD, she worked on a project related to the genetics of preterm birth and became fascinated by the interplay between epidemiology and genetics. She went on to pursue a postdoc at the University of North Carolina at Chapel Hill in the genetics department, where her research focused on diabetes.

“I was drawn to trying to figure out this puzzle, understanding how genetics, lifestyle components, and other risk factors all work together to determine health outcomes,” she says.  

Today, Spracklen’s research combines epidemiological, genetic, and bioinformatic methodologies to identify genetic variants associated with type 2 diabetes. Much of her work involves meta-analysis of all available data across large, genome-wide association studies, and it includes diverse, non-European ancestry populations who have been historically underrepresented in this type of research.

In 2024, Spracklen co-led an international team of researchers that published the largest genome-wide association study to date on type 2 diabetes in the journal Nature. Using cutting-edge computational approaches, they located 1,289 genetic markers associated with the disease—145 of which were newly identified—and generated risk scores for diabetes complications. They are currently working on an update to this work that nearly doubles the sample size to approximately 4.5 million people.

In 2026, they published another international study in Nature Metabolism, which revealed hundreds of genes and proteins likely to play a causal role in type 2 diabetes; it also highlighted the importance of looking beyond blood samples alone to study gene effects in diabetes-relevant tissues, including the pancreas, liver, and muscle.

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Chi “Josh” Zhao, a PhD student in the Spracklen Lab, is currently conducting research for his dissertation that attempts to integrate multiple polygenic risk scores for diabetes and associated cardiometabolic traits to better predict who will go on to develop the disease.

Beyond identifying genetic variants that increase diabetes risk, Spracklen aims to figure out the mechanism by which these variants are acting. “For example, are they increasing gene transcription, which is therefore creating some extra protein or enzyme in the body?” she says. Spracklen’s lab is collaborating with researchers at The Jackson Laboratory for Genomic Medicine on wet lab studies to understand how DNA variants may affect the genomic arc of pancreatic cells under different conditions. Ultimately, understanding the products of specific genes may lead to the development of new drugs to target those products—much as popular GLP-1 drugs like Ozempic and Wegovy target GLP-1 receptors found in the pancreas, brain, stomach, and heart. 

Zhao is also conducting ongoing research that seeks to cluster type 2 diabetes patients into different subtypes based on a number of clinical variables, including age of diabetes onset, BMI, renal function, and hemoglobin A1C (an indicator of average blood sugar levels over the past 90 days). He’s interested in whether certain subtypes are more strongly associated with different diabetes complications, including macrovascular complications (like cardiovascular disease and stroke) and microvascular complications (like diabetic kidney disease and diabetic retinopathy). 

“Understanding how diabetic subtypes are associated with certain complications may help guide clinical interventions in the future,” Zhao explains.

The group’s research also addresses how genetic variants interact with lifestyle behavior. In 2026, they published a study in the journal Diabetes suggesting that more than half of type 2 diabetes cases might be preventable with healthier lifestyle choices. The study, which analyzed data from more than 332,000 adults in the U.K. over a median period of 14 years, found several lifestyle factors that influence diabetes risk—most notably, BMI, as well as, to a lesser extent, physical activity, smoking, and diet—regardless of genetic predisposition.

“Even if you have a strong family history or high genetic risk, it’s not a foregone conclusion that you’ll develop type 2 diabetes,” Spracklen remarks. “Healthier lifestyle choices will mitigate your risk—even if you’ve lost the genetic lottery.”
 

A Future of Personalized Medicine

To date, the group’s research has contributed to the development of a fairly clear picture of the genetics of diabetes. In the future, Spracklen hopes this research will inform pharmacogenomics—the study of how one’s DNA affects the body’s response to medication. 

“We know that medications work better for some patients than others, and that some patients react poorly to certain drugs. A lot of that is due to biological or genetic differences,” Spracklen explains. “We’re moving toward this idea of personalized medicine, where a doctor can look at a patient’s genetic makeup and understand the implications of different genetic variants on their risk of developing diabetes as well as how they’ll respond to medications.”

This vision for personalized medicine is already becoming a reality in some small pockets of health care, including certain kinds of cancer care and, in the U.K., proactive therapies for children before the onset of type 1 diabetes. Spracklen believes personalized medicine could become much more widespread for treating diseases like type 2 diabetes in the next two decades; however, she says this will require not only continued research but also adequate funding, clinician training, public education, policies, and infrastructure.

“Ultimately, we’d like to have universal genetic testing early in life to allow for proactive screening and personalized treatment of diseases,” Spracklen says. “As we continue to learn more about the genetic contributors to different diseases, that information could be used to make a difference in everyday care.”

This story was originally published in July 2026.