Clinical Research in Diabetes and Obesity pp 357-382

Part of the Contemporary Biomedicine book series (CB, volume 15)

Syndrome X

Past, Present, and Future
  • Gerald M. Reaven
Chapter

Abstract

In 1988 I suggested that a defect in the ability of insulin to stimulate glucose disposal played a major role in the pathogenesis and clinical course of what are often referred to as diseases of Western civilization (1). It had been apparent for some time that resistance to insulin-mediated glucose disposal was a common finding in patients with noninsulin-dependent diabetes mellitus (NIDDM), and that fasting hyperglycemia supervened in such individuals when they no longer were able to sustain the degree of compensatory hyperinsulinemia necessary to overcome the defect in cellular insulin action (2–5). However, what was not as well appreciated was the fact that insulin-resistant subjects able to sustain the degree of compensatory hyperinsulinemia necessary to maintain near-normal glucose homeostasis were at risk of developing a cluster of additional abnormalities, including some impairment of glucose tolerance, a high plasma triglyceride (TG) and a low high-density lipoprotein (HDL) cholesterol concentration, and hypertension (1). This cluster of related abnormalities, all of which increase risk of coronary heart disorder (CHD), was designated as Syndrome X. Since that time, this formulation has received considerable support (6–8). Furthermore, the list of abnormalities associated with insulin resistance and compensatory hyperinsulinemia has grown to include higher serum uric acid concentrations (9),smaller and denser low-density lipoprotein (LDL) particles (10),accentuation of postprandial lipemia (11), and increased concentration of plasminogen activator inhibitor (PAI)-1 (12).

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