The Death of the
‘Thrifty Genotype’ :
Type-II Diabetes Among
Native American Populations
James T. Watson, Ph.D.
Indiana University-Purdue University Indianapolis
Department 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 up
to ~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 diluted
over 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 Security
Quantity of Available Food by Food Economy.
Rating (Rank)
% Forager (n)
% Agric. (n)
Plenty (1)
36% (10)
35% (23)
Adequate (2)
46% (13)
51% (34)
18% (5)
9% (6)
0% (0)
5% (3)
Subsistence (3)
Minimal (4)
Adapted from Whiting (1958:33-34)
Frequency of Food Shortages by Food Economy.
Rating (Rank)
Rare (1)
Occasional (2)
Annual (3)
Frequent (4)
% Forager (n)
% Agric. (n)
43% (12)
56% (37)
18% (5)
24% (16)
0% (0)
0% (0)
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)
39% (11)
23% (15)
Severe (3)
Adapted from Whiting (1958:33-34)
Food Availability and Security
Mann-Whitney U Test of Similarity
Between Forager and Agricultural Groups.
Avail.
Mann-Whitney U
Wilcoxan W
Z
Asymp. Sig.
Frequency
Extent
913.000
746.500
771.000
3124.000
2957.500
2982.000
-0.100
-1.610
-1.346
0.920
0.107
0.178
• 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
Hunter-Gatherer Complexity
Stereotype = “Hunter-gatherers move
around 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 history
of deprivation…expressed 40-50 years later
when risk-factors (e.g.-obesity) first emerged
in their communities.
Nature Genetics 19:209-210 (McCarthy, 1998)
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).
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 support
and 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