Fetal origin of maturity-onset diabetes mellitus: genetic or environmental cause?

Low birthweight is a risk factor for a number of diseases of adult life including non-insulin-dependent diabetes mellitus (NIDDM). This implies that either genetic constitution or factors operating during intrauterine development have a causal role in NIDDM. One reason for rejecting a genetic cause, however, is that there is a rapidly changing prevalence of NIDDM with the onset and establishment of affluence, which does not fit with conventional models of multifactorial genetic disease. But in this article a new model of genetic disease based on the concept of redundancy is explored. The idea is that mutant genes interact synergistically in highly redundant systems to degrade performance and increase the risk of disease. The mutational load is in turn determined by the pre-conceptual environment. This model can explain a rapidly changing prevalence of NIDDM.