PerspectiveIn the Journals

Physical activity less protective against type 2 diabetes in those more genetically predisposed

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September 30, 2014

The protective effect of physical activity against type 2 diabetes is weaker among people with higher genetic predisposition for the disease, according to research published in Diabetologia.

“The results from our study suggest the extent 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,” Yann C. Klimentidis, PhD, of the University of Arizona, told Endocrine Today.

Yann Klimentidis

Yann C. Klimentidis

“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,” he added.

Klimentidis and colleagues from the institution conducted a prospective cohort study to assess the relationships between physical activity, diabetes incidence and genetic susceptibility.

The investigators used data from 8,101 self-identified white men and women aged 45 to 64 years who participated in the multicenter, prospective Atherosclerosis Risk in Communities (ARIC) study; there were 821 incident type 2 diabetes cases within this group.

The researchers used the Baecke physical activity questionnaire, with a focus on the sport and exercise components of physical activity, to evaluate activity level.

They examined interactions between activity and: 65 single nucleotide polymorphisms (SNPs) associated with type 2 diabetes; a genetic risk score (GRS) comprising all 65 SNPs; two GRSs comprised of SNPs involved in insulin resistance and insulin secretion; and GRSs for fasting insulin and fasting glucose.

The interaction observed between physical activity and the type 2 diabetes GRS (P for interaction=.016) suggested a weaker protective effect of physical activity in people at higher genetic risk, according to the researchers.

Based on the interactions seen with the insulin resistance GRS (P for interaction=.046) and the fasting insulin GRS (P for interaction=.042), the overall type 2 diabetes GRS interaction more likely occurs through genetic susceptibility to insulin resistance than insulin secretion, according to the researchers. This interaction was more pronounced in women (P for interaction=.0025) than in men (P for interaction=.46). No single SNP displayed a strong interaction with physical activity.

The researchers noted using less subjective measures of physical activity, replicating the finding in another large prospective cohort, gaining a better understanding of the sex difference observed and generalizing the finding to other ages, ethnicities and races would be important for future studies.

“This study does put forward the possibility that prevention and treatment measures could be optimized based on a patient’s genetic information,” Klimentidis said. “Although major progress has recently been made in understanding the genetic basis of type 2 diabetes, our knowledge is still quite limited, and therefore not yet useful in a clinical setting, at least for vast majority of patients.” — by Allegra Tiver

For More Information: Klimentidis can be reached at Mel and Enid Zuckerman College of Public Health, Division of Epidemiology and Biostatistics, University of Arizona, 1295 N. Martin, Tucson, AZ 85724; email: yann@email.arizona.edu.

Disclosure: The ARIC study is a collaborative study supported by the National Heart, Lung, and Blood Institute. One researcher was supported by an NIH grant.

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PERSPECTIVE
Yehuda Handelsman

Yehuda Handelsman

The observation is nice and important. You can also take this study into a bit of a different dimension, addressing not just patients with type 1 diabetes but also patients with latent autoimmune diabetes in adults (LADA).

Today, many patients with type 1 diabetes are experiencing the same increase weight and inactivity just like the rest of the population increasing their cardiovascular risks. People with LADA have a similar presentation to the type 1 diabetes population, just later in life. They are diagnosed with positive antibodies and have similar autoimmune pathophysiology to type 1 diabetes, perhaps with a similar genetic relationship. The population with LADA are also not immune from the obesity epidemics, many have their condition accelerated by insulin resistance — consequent of obesity — and similarly develop CV risk.

Observing these populations, one can ask several questions: Would obesity and insulin resistance further aggravate and worsen the outcomes? Would this take place as part of the pathogenesis of the disease? We don’t know.

We know the surge of type 1 occurs in ages 5 to 7 years, and then again in ages 13 to 15 years, which coincides with puberty — and a time we find a high state of insulin resistance. From a clinical standpoint, and maybe simplistic, if a patient has an autoimmune condition causing a slow destruction of the islets that make insulin, and if on top of that process they would also have obesity and insulin resistance, which is so frequent in the society today, it would likely accelerate the development of frank diabetes and further subject them to risk of CVD.  

Examining patients with type 1 whose parents have type 2 diabetes they most likely also have insulin resistance — as it is accepted that type 2 diabetes is a familial condition, though the genetics are still being worked out — which may accelerate the development of diabetes as well as increasing their CV risk.  

Lifestyle modification, with reducing weight and increased physical activity, improves insulin sensitivity and glucose disposal, typically help people with type 1 diabetes, LADA & type 2 diabetes. However, we need to be aware of the fact that though lifestyle may halt or reverse progression to type 2 diabetes, in those people who also have autoimmune antibodies lifestyle may slow progression; however, the antibodies do not necessarily lose their ability to continue the destruction of insulin producing beta cells.

Thus the clinician ought to be able to recognize that some people who look like they have garden variety type 2 diabetes and yet their diabetes progression worsen, regardless of lifestyle modification, that they perhaps have something else going on, potentially genetically, causing further destruction of the islet cell. It is important to characterize these patients who are affected both genetically and environmentally where and when physical activity may not stop progression, though it could slow progression.

Continuing lifestyle modification in all patients, regardless of genetic risk or predisposition, is important. People with type 1 diabetes have learned that exercising improves their response to insulin therapy, helping them to achieve much better glucose control. It is also important to understand that in those patients with type 1 diabetes who are not obese, though good lifestyle should be part of their management, it’s not really necessary to always over restrict their diet because they can easily compensate with the appropriate amount of insulin. The clinician should exercise clinical sense addressing quality of life and individual management recommendations an approach which should be key part of this discussion.


Yehuda Handelsman, MD, FACP, FACE, FNLA
Medical Director and Principal Investigator, Metabolic Institute of America
President, American College of Endocrinology

Disclosure: Handelsman reports that he has received consultant and speaker fees and research grants from various pharmaceutical companies.