The hypertension advantage and natural selection: Since type 2 diabetes associates with co-morbidities and premature death, why have the genetic variants remained in the human genome?

• Published in: Medical hypotheses 2019-08, Vol.129, p.109237-109237, Article 109237
• Main Authors: Lewis, Matthew T., Lujan, Heidi L., Wiseman, Robert W., DiCarlo, Stephen E.
• Format: Article
• Language: English
• Subjects: A sedentary lifestyle; Animals; Blood Pressure; Comorbidity; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Exercise; Female; Genetic Variation; Genome, Human; Genotype; Goto-Kakizaki (GK) rat; Humans; Hyperglycemia; Hypertension - complications; Hypertension - genetics; Insulin - metabolism; Male; Models, Theoretical; Mortality, Premature; Obesity; Perfusion pressure; Rats; Rats, Wistar; Renin-Angiotensin System; Sedentary Behavior; Selection, Genetic; Sympathetic Nervous System - physiopathology
• ISSN: 0306-9877; 1532-2777
• DOI: 10.1016/j.mehy.2019.109237

Type 2 diabetes is a major public health crisis around the world. It is estimated that more than 300 million people worldwide have type 2 diabetes. Furthermore, the World Health Organization estimates that deaths from the complications of diabetes will increase by two thirds between 2008 and 2030. Since type 2 diabetes is a major public health crisis, why have the genetic variants for diabetes not been removed from the genome by natural selection? We hypothesize that insulin resistance, a predisposition to type 2 diabetes, and the associated elevation in sympathetic nervous system activity and arterial blood pressure provided an advantage to humans who lived as hunter-gatherers. Specifically, sympathetic hyperactivity stimulates the renin-angiotensin aldosterone system, promotes sodium reabsorption, and increases blood volume, heart rate, stroke volume and peripheral vascular resistance, thus inducing hypertension. The hypertension in turn provides a hemodynamic advantage for hunter-gatherers. Specifically, sympathetic hyperactivity and increased blood pressure increases blood flow delivery to working muscles by increasing cardiac output and shunting blood from non-active tissue. This natural selection for hypertension occurred during the time in human evolutionary history when the lifespan of most individuals was probably 30–40 years, and morbidity and mortality from cardiovascular disorders was limited. Thus, the selection pressure for elevation in sympathetic nervous system activity and blood pressure provided an advantage for hunting and gathering that would be greater than the selection pressure exerted by the manifestations of cardiovascular disease in aged individuals.