So go the Pimas, so go the rest of us

Anyone familiar with the American Southwest may have heard of the Pima Indians of south-central Arizona. The Pima are the modern descendents of the famous desert Hohokam who occupied vast swaths of south-central Arizona from roughly 200 BC to AD 1450. Famous among archaeologists for their massive and intricate canal systems built to deliver water to the arid and ecologically defiant agricultural fields of the parched Southwest, the Hohokam are a true success story of the ancient world.

While history paints the Hohokam as masters of their ancient environment, medical researchers fear our modern environmental landscape may be undermining their modern Pima Indian descendants.

In the 1960s epidemiologists started noting an alarming trend among the 11,000 or so Pima Indians living in the Gila River Indian Community just east of Phoenix, Arizona. For some unknown reason, a startling number of Pima were developing type 2 diabetes.

Diabetes affects tens of millions of Americans, resulting in the death of more than 300,000 people annually. It’s also the leading cause of end stage kidney disease, adult blindness and amputation. The prevalence of diabetes among African Americans is nearly 70% higher than in Caucasians. Like obesity, diabetes dominates our national discussion on health care.

But for the Pima, type 2 diabetes and its complications are acutely devastating. With the prevalence of diabetes estimated at 5.1% of the global population, and 7.9% of the US population, the 38% recorded among the Pima of central Arizona gives them the distinction of being the most diabetes-prone group on the planet.

Once the trend started rearing its ugly head in the 1960s, researchers saw not only a looming health crisis among the modern Pima, but also an opportunity to study the disease in a genetically ‘pure’ group, as many of the Pima married within their own community. Importantly, they had multiple generations within families in which to follow the development of the disease and the genetic predisposition. With millions in funding from the National Institutes of Health (NIH) and the blessing and cooperation of the Pima, the Phoenix Epidemiology and Clinical Branch of the NIH was established.

It is now several decades and 100 million dollars later, and researchers are still grappling with the Pima diabetes enigma.

So why are the Pima prone to diabetes? Diabetes research in general has determined that lifestyle (diet, smoking, physical activity, etc) and genetic factors clearly play a role. For example, there seems to be a significant correlation between ones weight and predisposition to developing diabetes and suffering from its complications. But among the Pima, given the genetic isolation of the group, it seems genes may play a major causal role in individual susceptibility. Or does it? A new study may shed some light.

If you happen to be thumbing through the latest issue of the journal Diabetes Care, you would have come across a fascinating study by researchers who examined and compared adult Pima Indians of central Arizona with their genetic cousins, the Mexican Pima of northern Mexico (see map here). As mentioned above, the Pima of central Arizona are descended from the ancient Hohokam, who originally migrated to southern Arizona from what is today northern Mexico (several hundred kilometers to the south). Based on genetic, linguistic, and archaeological data, this migration is thought to have occurred a little over 2,000 yrs ago. Not all of the ancient population migrated and settled in southern Arizona, however, some stayed behind to farm the highlands of Mexico. This situation has provided a unique opportunity for researchers studying diabetes and other diseases among the Pima of southern Arizona. On the one hand, you have Pima who have embraced the modern western civilization and its lifestyle (diet) as it swept over them, and on the other, you have genetically identical ‘cousins’ who essentially stayed on the farm.

The Mexican Pima live in remote areas of the Sierra Madre Mountains and enjoy few modern amenities. Much of these communities only recently became accessible by road. The Mexican Pima are primarily farmers and work manual labor jobs, such as those available in local saw mills. Almost every aspect of daily life includes physical activity.

In contrast, the Pima of southern Arizona, who were traditionally farmers, “enjoy” a typical US lifestyle of computers and TVs, with low levels of occupational physical activity. They have ready access to automobiles and mechanized farm equipment for those who still farm. Indeed, two very different worlds.

The researchers set out to test the following question by examining adults among the genetically similar but environmentally different sets of Pima: “Do type 2 diabetes and obesity have genetic and environmental determinants?” In other words, does environment (diet, obesity, physical activity, and other risk factors) play a role in the development of diabetes when you hold the genetic pool relatively constant? If genetics played a major role in the southern Arizona Pima’s astounding rate of type 2 diabetes, you would expect to see elevated levels in the Mexican Pima.

To add an additional variable to their study, the researchers also included Mexicans living in the same environment as the Mexican Pima in the Sierra Madre Mountains. The Mexicans (not of Pima heritage), are a mix of local Indians and Spanish. Like the Mexican Pima, the Mexicans live a rural and physically demanding life as farmers and ranchers.

Using Spanish-speaking interviewers and medical technicians, the data was collected. A brief medical history and  physical activity questionnaire was completed on each participating individual, followed by measurements of blood pressure, and a 75-g oral glucose tolerance test. The entire sequence was performed on 193 adult male and female non-Pima Mexicans and 224 Mexican Pima near the town of Maycoba in the Sierra Madre Mountains of northern Mexico. In addition, obesity was assessed by BMI (weight in kg divided by the square of the height in meters), body fat was measured, and waist-to-hip ratio was determined. On top of all that, a 24-hour dietary recall was conducted to determine what everyone was eating.

Using the data collected from these two groups, researchers compared the obesity, diet and prevalence of diabetes to some 888 Pima from southern Arizona. The prevalence of diabetes among the three groups is presented graphically below.

The prevalence of diabetes between the two genetically similar Pima groups is striking. Among the Mexican Pima men, 5.6% had diabetes, along with 8.5% of the women. Compare this to the Pima Indians of Arizona where 34.2% of the men have diabetes and 40.8% of the women. Among the non-Pima Mexicans (no shared heritage with the Pima), 5% of the women were diabetic and none of the men. That last part is worth repeating: none of the non-Pima Mexican men had diabetes!

In other words, age- and sex-adjusted prevalence of diabetes in U.S. Pima Indians was 5.5 times higher than their Mexican cousins and 16 times higher than the non-Pima Mexicans. The researchers also point out that the differences seen between the two Mexican groups was not significantly different (i.e., basically the same).

The differences between the prevalence of diabetes among the Pima Indians of Arizona versus the non-Pima Mexicans and Mexican Pima was also paralleled by differences in obesity, physical activity and diet.

BMI, percent body fat, waist and hip ratios were about the same among the two Mexican groups, but significantly different from the U.S. Pima Indians. The average non-Pima Mexican weighed in around 158 pounds (72 kg), with the average Mexican Pima at 145 pounds (66 kg). However, the average U.S Pima Indian male weighed 215 pounds (98 kg). While the women in all three groups weighed less, they followed much the same trend with U.S. Pima Indian females weighing, on average, about 200 pounds (91 kg).

As you may already sense, the levels of moderate to heavy physical activity among the groups was higher for the non-Mexican Pima and the Mexican Pima compared to the U.S. Pima Indians. For example, the average U.S. Pima Indian women spent 3.1 hours a week on moderate to demanding physical activity compared to 22 hours per week recorded for her Mexican Pima cousin.

As for diet, nothing glaring jumps out between the non-Mexican Pima and Mexican Pima – other than a remarkably low percentage of calories derived from fat, ~25%. In the current study, the researchers did not collect dietary data on the U.S. Pima Indians. Previous studies, however, reveal that percentage of calories from fat for U.S. Pima Indians was much higher than the 25% recorded for the Mexicans groups.

The dietary fiber measured in the diet among the non-Pima Mexicans and the Mexican Pimas deserves some special mention. No matter if they were male or female, non-Pima Mexican or Mexican Pima; they consumed greater than 50 grams of dietary fiber a day. Compare this to the 12 to 15 grams a day the average U.S. Pima Indian, or the average American for that matter, are consuming.

Given the similar genetic background between the U.S. Pima Indians and the Mexican Pima, the nearly fivefold increase in diabetes among the U.S. Pima can only be attributed to differences in lifestyle and environments.

While researchers continue to look for genes that make someone of a distinct genetic group susceptible to diabetes and other diseases such as heart disease, the current study among the westernized and nonwesternized Pima has taught us that obesity and physical activity have more to do with the likelihood that you will develop diabetes, regardless of your genetic makeup.

The take home message from the current study is profound: the genetic likelihood that you will develop type 2 diabetes is NOT inevitable and is CLEARLY preventable if you balance a reasonable amount of energy intake with energy expenditure and follow a diet low in westernized, highly processed foods.

However, the escalated levels of diabetes among the U.S. Pima and the increase of prevalence with age (for example, 77% of the U.S. Pima > than 55 years of age have diabetes) hint at some underlying genetic discordance with the modern food supply and environment. This is what keeps millions of tax dollars flowing into the genetic-arm of modern medical studies among the U.S. Pima Indians of southern Arizona.

I would add to the current study that the dramatic shift (drop) in dietary fiber in the U.S. Pima Indian diet from that of their Hohokam and earlier ancestors (who consistently consumed >100 grams of dietary fiber from a diverse variety of plants), has dramatically influenced the amount of insulin secreted throughout life contributing to the metabolic condition of insulin resistance – a complication associated with type 2 diabetes. This metabolic condition, which I call The Human Hybrid Theory, potentially affects all modern humans who have shifted away from a diversity and quantity of dietary fiber that our ancestors once enjoyed and that our genome was selected upon.

It is worth noting that the non-Pima Mexican men, a group that recorded the highest consumption of fiber at 56 grams a day, not a single case of diabetes was noted. Not one.


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