The rise and fall of the metabolic syndrome

Excerpt

The clustering of risk factors for diabetes and cardiovascular disease (CVD) has been known for many decades. The origins of the notion of insulin resistance as a root cause of some forms of diabetes go back to 1936 when Himsworth [1] proposed the subdivision of diabetes into an insulin-sensitive form and an insulin-resistant form, the latter typically associated with obesity. Even though a number of studies over the next decades identified additional CVD risk factors associated with diabetes and insulin resistance, it was only after Reaven’s publication in 1988 [2] that the literature really started to proliferate. Coming from the field of physiology, Reaven elegantly proposed a hypothesis that could explain the link between a number of CVD risk factors including glucose, offering the suggestion that insulin resistance could be the common denominator underlying a syndromic clustering of metabolic risk factors. In other words, he offered a pathophysiological model that could be tested, confirmed or rejected. What followed was not the design of studies to test this underlying model, but rather a plethora of studies confirming the basic associations or proposing new markers that were also associated with insulin resistance. In either case, the observational evidence of association was all too often taken as evidence of causality. The literature proliferation popularised the concept of the ‘metabolic syndrome’, which, like a young prince, grew rapidly from its baptism in 1988, confirmation by the WHO [3] in 1999 and ultimate coronation in heavily sponsored world conferences held in its own name. This ascent to the throne has not been without criticism [4], and recently the EASD and the American Diabetes Association (ADA) jointly declared in an extensive review of the topic [5] that: (1) the criteria are ambiguous and incomplete; (2) the rationale for thresholds is ill-defined; (3) the value of including diabetes in the definition is questionable; (4) the role of insulin resistance as the unifying aetiological factor is uncertain; (5) there is no clear basis for including or excluding other CVD risk factors; (6) the CVD risk value is variable and dependent on the specific risk factors present; (7) the CVD risk associated with the ‘syndrome’ appears to be no greater than the sum of its parts; (8) the treatment of the syndrome as a whole is no different from that of each of its components; and (9) the medical value of diagnosing the syndrome is unclear. …