Archaeology of NIDDM: Excavation of the “Thrifty” Genotype

Abstract

Since the 1940s, numerous cases of non-insulin-dependent diabetes mellitus (NIDDM) have been observed in certain American Indian populations. Extremely high prevalence rates of NIDDM occur most strikingly in several tribes of Paleo-Indians, whose ancestors migrated to North America greater than 11,000 yr ago. Archaeological evidence from that period indicates that certain groups of Paleo-Indians maintained an arctic-like hunter-gatherer life-style in an area in temperate North America ranging from Wyoming to Arizona. This life-style featured a reliance on unpredictable big game species as a major food source. However, at this time, big game species were becoming extinct. It is hypothesized that those Paleo-Indians who relied on big game as a food source developed a "thrifty" genotype that allowed a selective advantage during the periods of fasting that occurred between big game kills. It also is hypothesized that this thrifty genotype in these Indians may contribute to NIDDM when a sedentary life-style is adopted and food sources are constant. Because insulin resistance in muscle is a major feature of NIDDM, it is possible that insulin resistance per se is the phenotypic expression of the thrifty genotype.

Worldwide spatial genetic structure of angiotensin-converting enzyme gene: a new evolutionary ecological evidence for the thrifty genotype hypothesis

“…Yet, in contemporary societies, as food is usually available in unlimited amounts and life is sedentary, thrifty genes become deleterious, as they increase susceptibility to diabetes mellitus. [1][2][3][4]37 This hypothesis has been widely supported by epidemiological, [11][12][13] genetic and evolutionary researches. 4,14,15 In particular, some specific genes have been identified or considered as 'thrifty genes' (or 'thrifty SNP'), including calpain-10 gene and G-proteincoupled receptor 35 gene, 4 APOE*4 allele, 14 SNPs in FABP2, MTP, b3AR (the Trp64Arg SNP), apo-E, UCP2, UCP3-p, PPARg2, LEPR, adiponectin and so on.…”

“…However, in contemporary societies, as food is usually available in unlimited amounts, the 'thrifty genotype' no longer provides a survival advantage, but renders its owners more susceptible to obesity and diabetes. 5 Although variants of this hypothesis have formed the topic of vigorous debate, [6][7][8][9][10] there are many researches that tend to support this hypothesis, not only in epidemiology [11][12][13] but also in population genetics or evolutionary ecology. 4,14,15 One of the problems of using the 'thrifty gene' concept is that most individuals associate it with a metabolic trait related to a frugal utilization of fuel, which indeed was Neel's (1962) first intention.…”

The ‘carnivore connection’—evolutionary aspects of insulin resistance

“…With the sustained availability of food this protective mechanism became deleterious leading The 'carnivore connection' S Colagiuri and J Brand Miller to an increase in type 2 diabetes (Neel, 1962(Neel, ,1992. Subsequently others have suggested that insulin resistance is the phenotypic expression of the thrifty gene (Wendorf & Goldfine, 1991;O'Dea, 1991). On the other hand, Hales and Barker have proposed the 'thrifty phenotype' hypothesis which invokes maternal and infant malnourishment to explain the increase in modern day diseases (Hales & Barker, 1992).…”

Parálisis períodica hipocalcémica tirotóxica

“…La recuperación ocurre primero en los músculos que fueron últimamente afectados, en un periodo de tiempo entre 3 a 72 horas (2). El compromiso de motoneurona superior y de músculos respiratorios es raro, pero puede ser fatal (24). Hay hiporreflexia o arreflexia paradójica en un paciente que muestra signos de hipertiroidismo.…”