Type 2 diabetes, cardiovascular disease, and the evolutionary paradox of the polycystic ovary syndrome: A fertility first hypothesis

Abstract

Worldwide, the high prevalence of the Polycystic Ovary Syndrome (PCOS), a heritable cause of ovarian infertility, is an evolutionary paradox, which provides insight into the susceptibility of well-fed human populations to cardiovascular disease and diabetes. We propose that PCOS, Type 2 diabetes (T2D) and the Metabolic Syndrome are modern phenotypic expressions of a metabolic genotype attuned to the dietary and energetic conditions of the Pleistocene. This metabolic "Fertility First" rather than "Thrifty" genotype persisted at high prevalence throughout the entire agrarian period-from around 12,000 years ago until 1800 AD-primarily, we contend, because it conferred a fertility advantage in an environment defined by chronic and often severe seasonal food shortage. Conversely, we argue that genetic adaptations to a high carbohydrate, low protein agrarian diet, with increased sensitivity to insulin action, were constrained because these adaptations compromised fertility by raising the lower bound of body weight and energy intake optimal for ovulation and reproduction. After 1800, the progressive attainment of dietary energy sufficiency released human populations from this constraint. This release, through the powerful mechanism of fertility selection, increased, in decades rather than centuries, the prevalence of a genotype better suited to carbohydrate metabolism. This putative mechanism for rapid and recent human evolution can explain the lower susceptibility to T2D of today's Europid populations. This hypothesis predicts that the increasing rates of diabetes and cardiovascular disease, which typically accompany economic development, will be tempered by natural, but particularly fertility, selection against the conserved ancestral genotypes that currently underpin them.

Evo-Devo of Child Growth III: Premature Juvenility as an Evolutionary Trade-Off

“…But how can the fertility-limiting obesity and PCOS be attributed to evolutionary fitness? Corbett et al [62] argue that PCOS, type 2 diabetes and the metabolic syndrome are modern phenotypic expressions of a metabolic genotype attuned to the dietary and energetic conditions of the pre-agrarian meat-based, high protein, low carbohydrate diet, with a genotype adjusted for protein and gluconeogenesis as metabolic fuel, through insulin resistance. They further argued that this metabolic ‘fertility first’ rather than ‘thrifty’ genotype persisted at a high prevalence throughout the entire agrarian period from around 12,000 years ago until ~1800 AD because it conferred a fertility advantage in an environment defined by chronic and often severe seasonal food shortages.…”

Nutrition and Chronic Disease: Lessons from the Developing and Developed World

“…Africa and the Indian subcontinent) would have been under greater pressure to select thrifty genes. Historically, all populations worldwide have been under gene selection driven by famine [3], and the majority of this selection has probably been mediated through traits that influence fertility and reproductive success under marginal nutritional conditions [5]. Any such favorable genotypes may contribute to obesity, by favoring deposition of reproductively useful fat reserves in times of plenty [3], and to T2D, by favoring peripheral insulin resistance to benefit conception at low levels of BMI [5], and by displacing resources towards the fetus.…”

Nothing in medicine makes sense, except in the light of evolution

“…The same logic could be applied to other key nutrients such as salt and sugar. While the specific genes and regulatory elements involved are yet to be clearly defined (and are likely a large complex of interacting genes), the concept is supported by the high incidence of metabolic syndrome and diabetes in populations that were agrarian for a long time (e.g., Middle Easterners, South Indians, and Native American) and likely went through many cycles of nutritional boom and bust [30,49] Interesting correlations have also been proposed with the human propensity for chronic inflammation [69] and polycystic ovarian disease [13].…”