How Type 2 Diabetes Survived Evolution

Cotton farmers in Tajikistan, circa 2000. Laure Ségurel studied the genetic prevalence of type 2 diabetes in Tajik farmers and herders from Kyrgyzstan in central Asia.

Cotton farmers in Tajikistan, circa 2000. Laure Ségurel studied the genetic prevalence of type 2 diabetes in Tajik farmers and herders from Kyrgyzstan in central Asia. (photo via Wikimedia Commons)

Type 2 diabetes is a major public health crisis in the United States and around the world. The World Health Organization estimates that more than 300 million people have type 2 diabetes worldwide, and that deaths from complications of diabetes will increase by two thirds between 2008 and 2030.  The current epidemic is attributed to unhealthy lifestyles, obesity and lack of exercise, but if it’s so clearly damaging to health, how did it evolve in the first place? Shouldn’t the genetic variants for the disease have been removed from the human population by natural selection long ago?

A popular explanation is that insulin resistance, a predisposition to type 2 diabetes, actually provided a protective benefit to humans who lived as hunter-gatherers. Insulin resistance limits the body’s intake of glucose by muscle and liver cells, therefore allowing its storage by fat cells. The body could use this extra glucose, so the theory goes, during cycles of feast and famine when people couldn’t be sure of their next meal. This so-called “thrifty genotype” hypothesis was proposed by University of Michigan geneticist James Neel in 1962, and still holds a lot of sway in the scientific community.

Another similar explanation, called the “carnivore connection,” is that insulin resistance developed in hunter-gatherers and herders because they had a low-carbohydrate (and low glucose), protein-rich diet, resulting in the need to save glucose in the blood to make it accessible for the brain. This same resistance was no longer needed in early farmers, however, because they had begun to incorporate carbohydrates into their diets as they learned to cultivate grains.

Laure Ségurel, PhD, currently a postdoctoral researcher in the Department of Human Genetics, wanted to find out if type 2 diabetes variants really were beneficial in the past, leading to their increased transmission from generation to generation, and whether there are different selective pressures on these variants between populations of herders and farmers.

In a study published in the European Journal of Human Genetics, she and her colleagues from Evelyne Heyer’s lab in the Eco-anthropology and ethnobiology unit of the National Museum of Natural History in Paris, France, did a genetic analysis of two populations from central Asia, a group of Kyrgyz herders and one of Tajik farmers. Using this data, they were able to show that the genetic variants associated to the risk for diabetes weren’t the ones being selected in humans. Instead it was the variants providing a protective effect in regard to type 2 diabetes that happen to be favored by evolution.

Ségurel and her colleagues also pinpoint the time at which the protective variants began to rise in prevalence, between 5500 and 12,000 years ago at the beginning of the Neolithic period when humans began to shift from nomadic to herding and farming lifestyles.

Ségurel said she was surprised both by the nature of the advantageous variants (those with protective effects) and by how recently this selection happened.

“The expectation that we had is that it should be old, because it should be when we were hunter-gatherers,” she said. “This happened pretty recently, since farming arrived about 10,000 years ago.”

Under the thrifty genotype hypothesis, they should have seen evidence that the variants associated with increased risk for type 2 diabetes were being selected specifically before this point, to provide those extra stores of glucose for nomadic hunters always on the lookout for their next meal. Instead, they found evidence of selection for variants that protected for diabetes.

These protective variants could’ve provided an evolutionary advantage against the cold climate in these regions long ago, or inoculated people against diseases caused by pathogens. It’s not necessarily that protection against type 2 diabetes was helping these early farmers survive, but something else genetically related to it was.

“Metabolism is such a wide phenotype that’s associated to many things,” Ségurel said. “So it could be anything. We don’t really point to a direction for that.”

The irony now is that modern medicine essentially ensures that the genetic variants that lead to increased risk for type 2 diabetes will continue to be passed on from generation to generation. Despite the overall toll it takes on one’s long-term health, with proper treatment someone can certainly live a healthy enough life to have children, especially since the more damaging effects usually don’t manifest themselves until past the age of 45.

The silver lining of this is that as researchers like Ségurel learn more about the genetic basis of type 2 diabetes, and who might be more susceptible to it, they can develop more precise prevention strategies. Type 2 diabetes is sometimes called a “lifestyle disease” because changes to diet and exercise can prevent it. Being at risk for a disease because of genetics doesn’t necessarily mean you will get it.

Ségurel L, Austerlitz F, Toupance B, Gautier M, Kelley JL, Pasquet P, Lonjou C, Georges M, Voisin S, Cruaud C, Couloux A, Hegay T, Aldashev A, Vitalis R, & Heyer E (2013). Positive selection of protective variants for type 2 diabetes from the Neolithic onward: a case study in Central Asia. European journal of human genetics : EJHG PMID: 23340510

About Matt Wood (443 Articles)
Matt Wood is a senior science writer for the University of Chicago Medicine and editor of the Science Life blog.
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