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Exercise May Not Reduce Type 2 Diabetes Risk as Much in People with Increased Genetic Risk

“An interaction of genetic risk with physical activity on incident type 2 diabetes that appears to be driven principally through genetic risk to insulin resistance.”… 

Yann C. Klimentidis, PhD, of the University of Arizona Mel and Enid Zuckerman College of Public Health in Tucson, and colleagues wrote, “It has been well established that physical activity reduces type 2 diabetes risk. However, the extent of protection afforded by physical activity may differ according to genetic factors.”

Among 8,101 self-identified white participants, aged 45 to 64 years, in the Atherosclerosis Risk in Communities (ARIC) study, the researchers identified 821 cases of incident type 2 diabetes. In this cohort, they examined interactions between baseline physical activity and genetics and type 2 diabetes incidence.

The researchers studied interactions of physical activity with each of 65 genetic variants, or single-nucleotide polymorphism (SNPs), associated with type 2 diabetes; a genetic risk score (GRS) comprised of all 65 SNPs, two GRSs comprised of SNPs implicated in insulin resistance and insulin secretion; and GRSs for fasting insulin and glucose.

Physical activity was assessed using the Baecke Physical Activity questionnaire. Specifically, they focused on the sport and exercise components of physical activity.

Results revealed a significant interaction between physical activity and the type 2 diabetes GRS (P=.016). The researchers noted that this finding indicates that the protective effect of physical activity was diminished in those with a higher genetic risk for the disease.

Overall type 2 diabetes GRS interaction likely occurs through genetic susceptibility to insulin resistance vs. insulin secretion according to the interactions observed with the insulin resistance GRS (P=.046) and the fasting insulin GRS (P=.042), the researchers reported.

Data also showed that this interaction was more pronounced in women (P=.0025) compared with men (P=.46).

No single SNP appeared to exhibit a strong interaction with physical activity, according to the data.

“In conclusion, we have found an interaction of genetic risk with physical activity on incident type 2 diabetes that appears to be driven principally through genetic risk to insulin resistance,” the researchers wrote.

“In future studies, it will be important to use less subjective measures of physical activity, to replicate this finding in another large prospective cohort study, to better understand the sex difference observed, and to generalize this finding to other age and ethnic/racial groups.”

Practice Pearls:

  • This interaction was more pronounced in women
  • The findings indicate that the protective effect of physical activity was diminished in those with a higher genetic risk for the disease
  • An interaction of genetic risk with physical activity on incident type 2 diabetes appears to be driven principally through genetic risk to insulin resistance

Klimentidis YC et al. Diabetologia. 2014;doi:10.1007/s00125-014-3380-z.