Positive selection of type 2 diabetes genotypes - the glycaemic threshold hypothesis

Area of Science:

• Evolutionary biology
• Metabolic diseases
• Human genetics

Background:

• The high prevalence of type 2 diabetes (T2D) presents a paradox, as traditional explanations like overeating and inactivity do not fully account for it.
• Historical human populations often experienced negative energy balance, leading to potential hypoglycemia, which impairs fitness.
• Hypoglycemia can negatively impact reproductive and cognitive functions, suggesting a selective pressure against it.

Purpose of the Study:

• To propose a novel evolutionary explanation for the high prevalence of type 2 diabetes (T2D).
• To investigate the hypothesis that T2D phenotypes conferring resistance to hypoglycemia were positively selected during human evolution.
• To explore the link between hypoglycemia resistance and the co-occurrence of T2D with other metabolic and cardiovascular diseases.

Main Methods:

• This study is primarily theoretical, proposing an evolutionary hypothesis based on existing literature.
• It analyzes the potential selective pressures related to energy balance and hypoglycemia in ancestral human populations.
• It examines the physiological links between insulin resistance, hypoglycemia, and associated conditions.

Main Results:

• The study posits that T2D phenotypes, by conferring resistance to hypoglycemia, may have been advantageous in ancestral environments.
• This proposed positive selection could explain the current high prevalence of T2D.
• Insulin resistance, a key feature of T2D, is also implicated in other prevalent conditions, suggesting a common underlying mechanism.

Conclusions:

• The evolutionary advantage of hypoglycemia resistance offers a new perspective on the high prevalence of type 2 diabetes (T2D).
• This hypothesis may explain the frequent coexistence of T2D with atherosclerotic cardiovascular disease, metabolic syndrome, and polycystic ovarian disease.
• Understanding these evolutionary pressures could inform future research into T2D prevention and treatment.