Insulin and cardiovascular disease: biomarker or association?

In the 1980s prospective studies using whole populations suggested a relationship between insulin and cardiovascular disease, and these studies proposed that both metabolic and haemodynamic factors were associated with cardiovascular events. The initial analysis of the Paris Prospective Study (Diabetologia 19: 205-210), published in 1980, showed a positive correlation between insulin and cardiovascular events in healthy middle-aged policemen after a 5 year follow-up. In the Bedford Survey (Diabetologia 22: 79-84), also performed in the 1980s, a higher cardiovascular risk was demonstrated in diabetic patients and in those with borderline diabetes; however, in contrast to the Paris Prospective Study, insulin was negatively correlated to cardiovascular endpoints in the Bedford Survey. The initial enthusiasm for insulin as a cardiovascular risk marker was dampened when the 15 year follow-up data of the Paris Prospective Study (Diabetologia 34: 356-361) showed that the correlation between insulin and cardiovascular risk subsided with increased duration of follow-up. Despite the fact that hyperinsulinaemia was always strongly associated with other classical cardiovascular risk factors, univariate analyses usually failed to show a strong correlation between insulin and cardiovascular risk. The San Antonio Heart Study (Diabetologia 34: 416-422) performed in a bi-ethnic population that included a large proportion of Mexican-American participants again emphasised that insulin resistance may be the underlying factor associated with a cluster of metabolic and haemodynamic abnormalities. However, recently performed meta-analyses that included larger studies have not been able to confirm a critical role for insulin levels in cardiovascular risk. Indeed, it has been suggested that proinsulin or other factors may be better markers than insulin per se.