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Reply to R Baschetti

Department of Health Sciences, University of Wisconsin-Milwaukee
Phoenix Epidemiology and Clinical Research Branch, NIDDK, NIH, Phoenix, AZ
Department of Internal Medicine, Bingham and Women's Hospital, Boston, MA
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis

Dear Sir:

Baschetti favors the "genetically unknown foods" hypothesis as an explanation for data presented in our November article comparing resting metabolic rate and plasma leptin concentrations between Mexican Pima Indians and non-Pima Mexicans (1). While we concluded that neither of these factors are expressions of the "thrifty genotype", purported to explain the high prevalence of obesity and type 2 diabetes in Pima Indians living in the United States, our findings do not disprove the "thrifty genotype" hypothesis.

The thrifty genotype hypothesis, first proposed by Neel (2), is based on the observation that susceptibility to develop type 2 diabetes appears to be genetically determined. Therefore, although currently disadvantageous, the diabetes genotype must have enhanced survival at some point in the past, thereby promoting its evolutionary selection. One of the environmental changes that has made the genotype detrimental in current times is the switch from feast and famine conditions to those of constant feasting. The ready availability of food with high energy density is proposed as a trigger to the metabolic changes leading to diabetes.

Baschetti dismisses the "thrifty genotype" explanation as poorly convincing, particularly with regard to Pacific Island populations suffering epidemic levels of type 2 diabetes, since food in that region has long been available year round. Similarly, he argues, Europeans have low rates of diabetes despite the fact they have experienced famines in the past.

We disagree with Baschetti with respect to the totality with which dietary changes explain the propensity toward diabetes. High fat diets alone do not explain the large variability in diabetes prevalence between populations. For example, Baschetti's "genetically unknown foods" hypothesis does not elucidate why Alaska Natives with their high fat diet have little diabetes (3) while the disease is rampant among the Pimas of Arizona. More likely, populations vary in the spectrum of genes that interact with the environment and determine that population's liability to type 2 diabetes.

For Pacific Island populations, explanations for the thrifty genotype have been proposed based on body size and composition. Houghton (4) hypothesized that cold, long and inhospitable oceanic voyages gave a survival advantage to those Polynesians with a large body size. A high fat-free mass would generate more heat, and a stocky frame, with a lower surface area to body mass ratio, would minimize heat loss. In contrast, Europeans appear to represent a low risk population. As suggested by Swinburn (5) the unique history of Europe may have reduced the frequency of diabetes-enhancing genes or promoted genes that protect against type 2 diabetes.

While we agree that high-fat diets rich in cholesterol contribute to the difference in coronary artery disease mortality between the US and rural China, the logic that this negates the "thrifty gene" hypothesis eludes us. Furthermore, Stubbs' data (6) that Europeans are unable to defend energy balance when provided a high-energy density diet can be readily explained by the fact that the current level of energy expenditure is insufficient to match the increased energy intake. It is not necessary to invoke the "genetically unknown foods" hypothesis to explain this finding either.

REFERENCES

1. Fox CS, Esparza J, Nicolson M, Bennett PH, Schulz LO, Valencia ME, Ravussin E. Is a low leptin concentration, a low resting metabolic rate, or both the expression of the "thrifty genotype"? Results from Mexican Pima Indians. Am J Clin Nutr 1998;68:1053–7.[Abstract]
2. Neel JV. A "thrifty" genotype rendered detrimental by "progress." Am J Hum Genet 1962;14:353–62.[Medline]
3. Schrafer CD, Bulkow LR, Murphy NJ, Lanier AP. Diabetes prevalence, incidence and complications among Alaska Natives, 1987. Diabetes Care 1993;16:257–259.[Abstract]
4. Houghton P. Selective influences and morphological variation amongst Pacific Homo sapiens. J Hum Evol 1991;21:41–51.
5. Swinburn BA. The thrifty gene hypothesis: How does it look after 30 years? Diabetic Med 1996;13:695–699.[Medline]
6. Stubbs RJ, Johnstone AM, O'Reilly LM, Barton K, Reid C. The effect of covertly manipulating the energy density of mixed diets on ad libitum food intake in `pseudo free-living' humans. Int J Obes 1998;22:980–7.

This Article Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Schulz, L. O Articles by Ravussin, E. Search for Related Content PubMed Articles by Schulz, L. O Articles by Ravussin, E. Agricola Articles by Schulz, L. O Articles by Ravussin, E.