vendredi 29 novembre 2013

THRIFTY GENE TO METABOLIC SYNDROME : HOW THE HUNTER GATHERERS BECAME OVERWEIGHT OR OBESE

LOW HDL CHOLESTEROL AMONG AMERICAN INDIANS, HYPERCHOLESTROLEMIA IN JAMAICA AND A CUBAN/AUSTRALIAN MEDICAL ANTHROPOLOGIST
In the Medical Literature, there has been a lot of hullabaloo made about the importance of a Low HDL Cholesterol, the so called Good Cholesterol and millions of dollars spent by Pharmaceutical companies to find a drug to raise it, but to no avail. Also they sadly found out that manipulating the HDL cholesterol to a higher level does not actually benefit the Heart!
The Low HDL cholesterol levels among the group I work with, The Indians of North America have puzzled me.  Also had become aware of the fact that HDL cholesterol is lower among many groups. The only common link I could find was one of change in Lifestyle in conjunction with Oppression or Alienation.
Science offered no help until recently when I read an article from our colleagues from Mesoamerica. Mexican researchers studying various American Indian groups were able to make some observations about ABC A1, ATP binding Cassette Transporter A 1 gene associated with low HDL cholesterol. They also found an association between this gene and Obesity and Type 2 Diabetes.
ABC A1 plays a key role in the cholesterol efflux and transfer from peripheral cells to lipid poor Apo lipoprotein A1 (ApoA1) the first step in the HDL particle formation.
A variant of this gene, C230, has only been found in Native Americans. No other groups in the world, Africans, Melanesians or Chinese have this allele.
This finding has tremendous implications.
From Western Alaska (Aleutian Islands) to Tierra del Fuego (Chile and Argentina) there are millions of Native Americans and in countries like Mexico, Guatemala, Peru and Bolivia there are millions more descendants of Native Americans. It is present across language divides among the Native Americans, decreasing only in the colder climates, which they postulate to be climate related adaptive processes.
(C230 allele in various native american groups, absent in other groups from other countries)
Overall, HYPOALPHALIPOPROTEINEMIA (HA) was the most common form of dyslipidaemia in this study: 65 percept of Mexican and South American Natives had it.
This variant is also associated with Obesity (which may have been contributed by the Newcomers to the continent from Europe, who were not known for their kindness, by forcing lifestyle changes).  Most Native Americans in South America are not obese but most North American Native American groups are overweight or obese.
What is very interesting is that, this allele is exclusive to Native Americans and their descendants.
Mexican Americans as they are labelled in the USA are not Native Americans but they have a fair bit of Indian admixture, and this is blamed for the high rate of obesity and type 2 Diabetes among them in the USA and also in Mexico (much evident after the North American Free Trade Agreement),
In 1962, Dr JV Neel had hypothesized a “Thrifty Gene” theory. Working closely with American Indians and observing other indigenous people, I strongly believe in the presence of this “thrift” in the metabolism of Indigenous peoples.
In the hunter-gatherer populations such as the Native Americans, the R230 C carriers could have had a selective advantage. Its presence prevents cholesterol efflux; this could favour intracellular cholesterol and energy storage during the times of Famine.
This natural protection became a curse. During famine, it accommodated the fluctuations in energy, provided energy for important functions such as Reproduction and more importantly the Immune System. (Which costs a lot of energy to maintain!)
It is not this genetic variant cursed the American Indian to become overweight and obese, but this trait became a liability when contact with outsiders created a lifestyle change, with increasing Body Mass Index, Type 2 Diabetes etc.
So by itself low HDL-C in an Indian or Indian descendant is not a disease, but a hint, in the modern times, to look elsewhere: Lifestyle changes and an important signal to counsel them on a Lifestyle change to one that resemble their Ancestral Lifestyle. This may also be partially responsible for the Fatty Liver seen among Native Americans and Mexican Americans.
Just around the time I began working with American Indians, I was also running Free Clinics for the Rural Poor in Jamaica who had high rates of Hypertension and Diabetes. To run these clinics, one needed help from all sectors of that very divided society. A prominent family had consulted their Endocrinologist in Miami (rich Jamaicans to this day seek their medical care in Miami), he had told them, both the mother and daughter had high cholesterol levels and had prescribed treatment of the day, which were creating some complications. In those days, when requesting Cholesterol levels one got different Lipoprotein factions and unlike today, no calculated values are recorded. (That is why in most of today’s lab reports; the sum of the calculated cholesterol values may be higher than the total cholesterol reported). Some friends at the University of Miami Chemical Pathology department afforded me some free testing of blood; I tested all the family members. Even I, as a novice endocrinologist but very well interested in medicine outside the body, could see that all members of the family were healthy, without any evidence of heart related conditions or risk factors for such. I was gratified to present the report to the family that they had HYPERALPHA LIPOPROTEINEMIA, something quite opposite to what I had been discussing above.
How to tie it all together? To complete the circle so to speak?
Rescue arrived in the form of research from Sao Paolo endocrinologists (published on 22 November 2013). They had hypothesized that plasma HDL-C concentrations independent of Overweight and Obesity might be influenced by Insulin Sensitivity.
One is reminded of all the pharmaceutical attempts to raise the HDL-C, which has ended up in failure so far!
In their studies of measurements of various proteins, in lean, low HDL C and high HDLC (like our Jamaican friends in question) they demonstrated that the protection offered is related to Insulin Sensitivity!
This observation has tremendous implications for the non-European, non-African populations of this world and especially with the groups that I work with: The Indigenous peoples.
In a paper published in 1972, the mavens of the media, later the troubadours of tragedy, those epidemiologists studying the Pima Indians, trumpeted:
Unexplained Hyperinsuinaemia among the PIMA Indians compared to the Caucasians.
Diabetes 26: 827-840, 1972
Insulin Sensitivity, Insulin Resistance and Diabetes among the groups I work with have been in my thoughts for years, trying to make sense of it all, away from the pronouncements based on other races and other countries, irrelevant socially, economically to the tragic reality of the Indigenous peoples.
An erudite colleague of mine from University of Texas Medical Branch at Galveston, Dr Charlie S, had asked me to look for the prevalence of Acanthosis Nigricans (the dark velvety markings on the nape of the neck one can easily see) among the Native Americans. A casual survey was surprising. Up to 1/5 children and 1/3 adults had this marking. For the next five years, we systematically did anthropometric measurements on hundreds of Indian children and dutifully recorded them. We couldn't fully understand the significance of Acanthosis Nigricans in Indian children, until Dr Charlie S, found a way to measure insulin levels without being too intrusive.

 Antibodies to insulin were incorporated into circles in a blotting paper to which one drop of blood was applied, which later was mashed up and measured for insulin levels.
Imagine our surprise when we found out that almost all American Indian children had higher than normal levels of Insulin levels and those with Acanthosis Nigricans had higher Insulin levels.
(it was my pleasure to travel to Tsumkwe in Namibia and check the Insulin levels of Healthy San Hunter Gatherers and as expected it was higher than normal, no obesity or Diabetes known among them)
It also fitted into the Thrifty Gene theory, which necessitated a storage hormone to store the energy at times of plenty and to release it when there was a shortage of energy. Insulin was the strong contender
for it. And still is!
From this and an anthropological analysis, I was able to put forward a holistic explanation.
Indians were and some of them are still INSULIN SENSITIVE, which protected them against
Obesity
Type 2 Diabetes
Non alcoholic Fatty Liver Disease.
The onslaught of outsiders with their peculiar lifestyle and eating habits, combined with oppression, powerlessness, alienation and marginalization became INSULIN RESISTANT.
It is this conversion that makes them overweight, obese, dyslipidaemic and Diabetic.

Here is where the Anthropological education comes in handy. It differs dramatically from the Biomedical Education such as we are given at Medical School in that it is
Qualitative
It asks the question WHY and not tries to answer it with WHAT which is what the biomedicine does
It takes into consideration the lived in life of the person rather than just the body as it happens in Biomedicine.

My erudite friend from Miami, has this capacity to ask WHY? And he can come up with searing answers that light up another pathway. He asked me, what if HDL-C is just a marker for something else. Here is your answer, my dear friend: It is.
We will ask some more WHY!
Studies like this help us alleviate the suffering of the Indigenous people of OUR AMERICA.
Thank you, dear researcher friends from Meso America and Brasil!
And to Brunel University for giving me such a wonderful Medical Anthropology education.
At a conference given at the Potawatomie Tribe of Kansas in 2006, I had suggested that social factors converted them from being Insulin Sensitive to Insulin Resistant.