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Several models have been proposed to explain the high prevalence of non-insulin dependent diabetes mellitus (NIDDM) and other diseases among New World populations. This paper examines the implications of a northern hunting adaptation (reliance on animal foods, seasonal shortages) in terms of energy digestion, absorption, metabolism and storage. Physiologic adaptations to a high protein, moderate fat, low carbohydrate diet are then examined in the context of agriculturally-based subsistence systems and in industrialized societies. Specific metabolic pathways, consistent with the work of both Neel and Weiss, are identified as fruitful areas for further research regarding genetic variants in New World populations.