Permanent impairment of insulin resistance from pregnancy to adulthood: The primary basic risk factor of chronic Western diseases

Summary 

Besides its well appreciated role in diabetes, obesity, and metabolic syndrome, insulin resistance (IR) is associated with smoking, use of hormonal contraceptives, androgens, glucocorticoids, beta-adrenergic blockers, thiazide diuretics, intake of food with high glycaemic index, and reduced physical activity. IR increases serum hormone levels of insulin and insulin-like growth factor-1 (IGF-1), which are most important mediators of cell proliferation, differentiation and inhibitors of apoptosis. Milk and dairy are introduced as new risk factors inducing IR, the physiologic growth-promoting principle of mammalian milk. This hypothesis explains IR as the underlying pathophysiologic mechanism of all major risk factors of chronic Western diseases. Evidence will be provided which supports that Western life style permanently boosters IR from intrauterine life to senescence. It becomes detrimental when the human intrinsic insulin/IGF-1-axis is continuously superimposed by external IR-potentiating effectors. This hypothesis can be proved by monitoring and proper adjustment of all aggravating effectors of IR. An all-encompassing consideration of IR-inducing risk factors from the beginning of life to adulthood appears to be of crucial importance for the prevention and treatment of chronic Western diseases.

Abbreviations: ACTH, adrenocorticotropic hormone, AGA, appropriate for gestational age, AMP, adenosine monophosphate, AMPK, AMP-activated kinase, CVD, cardiovascular disease, DHEAS, dehydroepiandrosterone sulfate, DHT, dihydrotestosterone, GDM, gestational diabetes mellitus, GH, growth hormone, GHR, growth hormone receptor, GLUT, glucose transporter protein, IGF, insulin-like growth factor, IGFBP, IGF binding protein, IGF1R, IGF-1 receptor, IGF2R, IGF-2 receptor, IR, insulin resistance, LH, luteinizing hormone, LGA, large for gestational age, MAPK, mitogen activated protein kinase, PCOS, polycystic ovary syndrome, PGH, placental growth hormone, PI3K, phosphoinositide-3-kinase, SGA, small for gestational age, SREBP, sterol response element binding protein