The Death of the‘Thrifty Genotype’ :Type-II Diabetes Among Native American Populations

James T. Watson, Ph.D.Indiana University-Purdue University IndianapolisDepartment of Anthropology

Diabetes

• Diabetes is a disease in which the body does not produce or properly use insulin.• Insulin = hormone needed to convert

sugar, starches and other food into energy.

• Affected in US (ADA):• Diagnosed: 14.6 million people• Undiagnosed: 6.2 million people• Pre-diabetes: 54 million people

• The cause of diabetes continues to be a mystery… both genetics and environmental factors (obesity and lack of exercise) appear to play roles (ADA).

Diabetes

• Type 1 (IDDM): autoimmune disease results in the body's failure to produce insulin.• Only ~5-10% of Americans diagnosed with type 1.

• Type 2 (NIDDM): results from insulin resistance, and relative insulin deficiency.• Most Americans diagnosed have type 2.

• Gestational: high blood sugar (glucose) levels during pregnancy.• Affects ~4% of all pregnant women.

A Native Disease

• US Native Americans: prevalence upto ~50% of adults over age 35(highest rates in the world)

Prevalence Groups (Young, 1990):• High = >30% (e.g. - Pima, Havasupai, Oji-Cree)

• Moderate (intermediate groups)

• Low = <10% (e.g. - Aleut, Eskimo/Inuit, Sub-Arctic

Athabaskans)

Culture History

• Intruders and reservation life (post-1600)…• Subjugation• Poverty• Poor nutrition and starvation

• Post-1950 increases in resources

A Native Disease of Global Scale

• Canada: prevalence rates among First Americans vary from 2-40%.

• Hawaii: native Hawaiians have a diabetes-related mortality rate 6X that for general U.S. population.

• High rates also found among native peoples throughout the world.

from Diamond (2003)

Explanations

‘Thirfty Genotype’ Model (Neel, 1962; 1982; 1999)

• 99% of human history as hunter-gatherers experiencing feast and famine cycles.

• Postulated existence of metabolically ‘thrifty’ genes....individuals with a ‘thrifty’ metabolism favored (selective advantage).

Thrifty Genotype

Thrifty Genes:

• Individuals with high levels of insulin or a “quick insulin trigger” for better fat storage…more efficient food utilization and rapid weight gain at times of food abundance.

• Thrifty genotype is maladaptive with modern, steady high-calorie diets and sedentary lifestyle.

• Recently acculturated native groups experience high rates of type 2 diabetes…the result of ‘telescoping’ genes that Europeans dilutedover many generations (Neel, 1982).

Genetic Disease???

• Type-I genes?• HRA alleles DR3 and DR4

• Type-II gene(s)? Polygenetic?• ADRB3, G308A, G250C (Jaquet et al., 2002)• D11S4464 (Duggirala et al., 2003)• Chromosome regions 3q21-q24, 4p15-q12,

9q21, 22q12-q13 (Baier and Hanson, 2004)• Etc…

• Diabetes epidemic among zoo primates.• Shared genes? (Diamond, 2003)

Genetic Determinism

• Genetic models guide modern research paradigms…

“Type 2 diabetes is a lifestyle disorder with the highest prevalence seen in populations that have a heightened genetic susceptibility; environmental factors associated with lifestyle unmask the disease” (Diamond, 2003).

• But modern DNA links inconclusive…

Testing the Thrifty Genotype

• Test basic assumptions of Thrifty Genotype Hypothesis…• Quantitative assessment of food availability and

security• Analyzed data from nutritional assessments of 118

global societies (Whiting, 1958) representing basic economic dichotomy proposed by Neel (1968).

From Benyshek and Watson (2006)

Food Availability and SecurityQuantity of Available Food by Food Economy.

Rating (Rank) % Forager (n) % Agric. (n)

Plenty (1) 36% (10) 35% (23)

Adequate (2) 46% (13) 51% (34)

Subsistence (3) 18% (5) 9% (6)

Minimal (4) 0% (0) 5% (3)Adapted from Whiting (1958:33-34)

Frequency of Food Shortages by Food Economy.

Rating (Rank) % Forager (n) % Agric. (n)

Rare (1) 43% (12) 56% (37)

Occasional (2) 18% (5) 24% (16)

Annual (3) 0% (0) 0% (0)

Frequent (4) 39% (11) 20% (13)

Adapted from Whiting (1958:33-34)

Extent of Food Shortages by Food Economy.

Rating (Rank) % Forager (n) % Agric. (n)

Mild (1) 32% (9) 41% (27)

Moderate (2) 29% (8) 36% (24)

Severe (3) 39% (11) 23% (15)Adapted from Whiting (1958:33-34)

Food Availability and Security

• No significant differences (α = .05) exist between foragers and agriculturalists with regard to…• Quantity of food available• Frequency of food shortages• Extent of food shortages

Mann-Whitney U Test of Similarity

Between Forager and Agricultural Groups.

Avail. Frequency Extent

Mann-Whitney U 913.000 746.500 771.000

Wilcoxan W 3124.000 2957.500 2982.000

Z -0.100 -1.610 -1.346

Asymp. Sig. 0.920 0.107 0.178

Hunter-Gatherer Complexity

Stereotype = “Hunter-gatherers movearound a lot and live in small groups”

• Based on extant, marginalized groups.

Conditions for more complexity…• Higher-than normal pop, concentrated in

relatively small areas such as river valleys and coastlines.

• More diverse, specialized food gathering.• Highly developed food procurement and

processing technologies.• Food storage and preservation.• Permanent (or nearly) settlements.• Division of labor.• Simple social ranking.• Trade.• More elaborate ritual and ceremonial beliefs.

Natural Selection and Thrifty Genes

No archaeological evidence for episodes of natural selection for ‘thrifty genes’• Demographic transitions

•40,000 bp (Paleolithic revolution)

•15,000 bp (first Americans)•10,000 bp (Neolithic revolution)

• Pima (2000 BC)• Europeans (4000 BC)

Alternative Explanations

Phenotypic Plasticity…”Thrifty Phenotype Hypothesis” (Hales and Barker, 1992):

• Native Americans with high rates share historyof deprivation…expressed 40-50 years laterwhen risk-factors (e.g.-obesity) first emergedin their communities.

Developmental Origins (Barker, 1998):

• Type 2 Diabetes passed on to later generations via hyperglycemic pregnancies.

• Deprivation followed by periods of overnutrition and reduced activity, then passed on through phenotypic plasticity (fetal physiological responses).

Nature Genetics 19:209-210 (McCarthy, 1998)

New Approaches to Prevention

• Improved prenatal care/nutrition may be best hope to slow or reverse the epidemic in high prevalence communities (Benyshek, 2005)

• In Native American communities, prevention efforts that acknowledge fetal programming research are likely to:• Resonate better with local explanatory and folk

models of diabetes etiology

• Provide real sense of hope for the future health of the community

• Thus, likely enjoy greater community supportand participation in local prevention programs

Society and Disease

• Type 2 Diabetes: Result of maladaptation to our cultural environment (food and activity).

• Cultural explanations…• Cultural trauma• Hypertension among African Americans