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UA Study Finds the Benefits of Physical Activity for Diabetes Prevention are Weakest among Women at High Genetic Risk

Yann Klimentidis, PhD

It is well established that physical activity reduces type 2 diabetes risk. Millions of Americans count on exercise as a way to protect against this chronic disease.

New research from the University of Arizona Mel and Enid Zuckerman College of Public Health suggests the protective effect of physical activity against diabetes is weakest among those at high genetic risk. The study is published this month in Diabetologia, the journal of the European Association for the Study of Diabetes.

The researchers examined the interaction of 65 type 2 diabetes-associated genetic variants, collectively and individually, with each individual’s baseline level of physical activity on incident type 2 diabetes in a prospective cohort study.

In an interview with Healio, lead researcher Yann Klimentidis, PhD, assistant professor of epidemiology at the UA Zuckerman College of Public Health, said, “Although physical activity can protect against type 2 diabetes, the extent of this protection might be stronger or weaker in some individuals, due to their genetic profile. The results from our study suggest that this level of protection is weakest among those with a high level of genetic risk for type 2 diabetes, and specifically, a high level of genetic risk for insulin resistance. The bottom line is that, although this area of research is still in its infancy, prevention and treatment measures for type 2 diabetes could eventually be more precisely tailored to an individual’s genetic profile.”

The researchers used data on 8,101 self-identified white participants in the Atherosclerosis Risk in Communities study (ARIC). The ARIC study is a multi-center prospective study of atherosclerosis in men and women between 45 and 64 years of age. Within this cohort, there were 821 incident type 2 diabetes cases. The researchers studied interactions of physical activity with 1) each of 65 type 2 diabetes-associated SNPs, 2) a genetic risk score (GRS) comprised of all 65 SNPs, 3) two GRSs comprised of SNPs implicated in insulin resistance and insulin secretion, and 4) GRSs for fasting insulin and glucose.

Each individual’s level of physical activity was assessed through the Baecke Physical Activity questionnaire, a standard assessment tool. The researchers focused on the sport and exercise components of physical activity.

Dr. Klimentidis and colleagues found a significant interaction of physical activity and the type 2 diabetes GRS, suggesting a weaker protective effect of physical activity in those at high genetic risk. Based on the interactions observed with the insulin resistance GRS and the fasting insulin GRS, it appears that the overall type 2 diabetes GRS interaction most likely occurs through genetic susceptibility to insulin resistance, as opposed to insulin secretion. Furthermore, this interaction was more pronounced in women than in men. No single SNP stood out as displaying a strong interaction with physical activity.

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