The
metabolic syndrome (or syndrome X) is a constellation of risk factors including
insulin resistance,
hypertension,
dyslipidemia, and
central obesity that predispose to the development of
cardiovascular disease and
type 2 diabetes in adult life.
Insulin resistance is believed to be a critical pathophysiological event early in the disease process, impacting both skeletal muscle metabolic function and vascular responses. Adverse changes in
insulin sensitivity have been found to originate in utero; for instance, prenatal events such as
placental insufficiency/oxidative stress leading to altered fetal growth trajectories are associated with increased rates of
metabolic syndrome in adult life. Such intrauterine insults result in reduced skeletal muscle mass in conjunction with altered
insulin signaling, decreased oxidative fibers, and impaired mitochondrial function. These developmental disturbances set the stage for development of muscle
triglyceride accumulation and depressed
insulin sensitivity in childhood. Abnormalities of vascular structure and function arising from deprived intrauterine conditions that are exacerbated by
insulin resistance account for the progression of
hypertension from childhood to adulthood. Arterial changes initiated in utero include reduced endothelial
nitric oxide (NO) bioavailability, vascular smooth muscle cell proliferation and
inflammation, events leading to endothelial dysfunction, and
atherosclerosis that are present in those destined for
metabolic syndrome. In addition, the hypertensive phenotype that is a hallmark of
metabolic syndrome may also be traced to blunted kidney development and renin-angiotensin system activation in growth-restricted offspring. The summative impact of these intrauterine programmed changes in terms of influencing adult health and disease encompasses dietary and lifestyle factors introduced postnatally. Establishing novel therapeutic interventions aimed at preventing and/or reducing in utero-induced
insulin resistance and vascular dysfunction warrants investigation because the numbers of low
birthweight babies continue to increase.