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Do genes or the environment play a bigger role in the development of type 2 diabetes?
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The heritability of type 2 diabetes is 40%, but some people might be the unlucky ones who inherited more risk variants than average.
We know from twin studies, family studies and family history studies that diabetes is heritable. The lifetime risk for developing type 2 diabetes is almost 70% if both parents are affected.
Type 2 diabetes is what we call a complex, polygenetic and multifactorial disease. When we say “polygenic,” a lot of genetic variants contribute to a person’s genetic susceptibility — some people may have a low genetic risk, whereas others may have a high genetic risk, but most of us have an average risk. While the heritability gives you an idea of how much genes contribute to variation in type 2 diabetes susceptibility in the overall population, a polygenetic risk score determines how many risk variants a person inherited from both parents. Thus, using this score, you can stratify the population by who is more genetically prone and who is less.
Currently available polygenetic risk scores are not very good at distinguishing those who might be more vs. less susceptible, and further improvement of the scores is needed before they can be used in a clinical setting.
While genetics are important, we always need the environment. Genes are the loaded gun, and the environment is the trigger.
For example, we know that people who carry two risk alleles will develop type 2 diabetes at an earlier age. TCF7L2 was identified more than 10 years ago and has the biggest effect on type 2 diabetes risk among all genes identified so far. However, studies suggest that people with these risk alleles who live a healthier lifestyle develop type 2 diabetes at a rate similar to people who do not have these risk alleles. That said, these people will always have to work harder to lower their risk for the disease.
Ruth Loos, PhD, is a professor of preventive medicine and director of the Genetics of Obesity and Related Metabolic Traits Program at the Icahn School of Medicine at Mount Sinai, New York. Disclosure: Loos reports no relevant financial disclosures.
There is increasing evidence around the world that the environment is contributing to the global epidemic of type 2 diabetes.
The background to this is, across the United States, we see a disproportionate impact of diabetes cases by race and ethnicity. We do not believe that this is simply related to genetics or poor lifestyle choices. We think there is much more to this, probably within the realm of the social determinants of health.
For example, here in Santa Barbara, California, it appears that an individual’s ZIP code is relevant when it comes to the risk for premature death from diabetes. We believe that this needs more exploration. At Sansum Diabetes Research Institute, we are partnering with the Bren School of Environmental Science and Management at the University of California, Santa Barbara, to collect information on the five determinants of health, which are genetics, biology, psychology, behavior and the environment. Bren students will assess existing big data sets measuring air quality and particulate matter. We want to link these data with where we see clusters of type 2 diabetes to see if there is a relationship between where you live and the risk for type 2 diabetes. Eventually, we want to start putting in local sensors so we can prospectively capture the data.
Globally, epidemiologists are pointing to the changing environment as a driver of diabetes. Let’s use China as an example. As China became industrialized, pollution levels increased and diabetes rates exploded. Now, of course, there are contributions from the Americanization of their food chain, but there is persuasive evidence from big data sets of a relationship between particulate matter in the air and diabetes risk. Recent data also suggest a relationship in China between particulate matter and risk for obesity. The mechanism seems to be that exposure to these particulate matters causes a low-grade inflammation, which can then lead to insulin resistance. If you are genetically wired, or you have the influence of the social determinants of health, then that is a perfect storm for developing type 2 diabetes.
The good news is that people are becoming increasingly environmentally conscious. These data add value to the need to protect the environment to protect human health from chronic disease. Think of the massive savings for health systems and the global impact of reducing the continuing pandemic of type 2 diabetes. This problem is not going to be treated by pharmaceuticals. This is going to be treated with health policy, environmental changes and regulation. Even if you’re not a believer in the concept of climate change, the impact of improving air quality will have the positive benefit of reducing incidence of type 2 diabetes as a spin-off.
David Kerr, MD, FRCPE, is director of research and innovation at Sansum Diabetes Research Institute in Santa Barbara, California, and director of mHealth Services for the Diabetes Technology Society. Disclosure: Kerr reports no relevant financial disclosures.