Fasting proinsulin showed a weak but significant correlation with common carotid artery intima-media thickness (r=0.07, P=0.029), which was markedly attenuated after adjustment for PAI-1.
Observational (n=985)
Are proinsulin and insulin concentrations associated with carotid intima-media thickness in nondiabetic subjects?
Proinsulin has a weak association with carotid IMT that is stronger than insulin but is largely attenuated by adjustment for PAI-1, suggesting it may be a marker rather than a causal factor for atherosclerosis.
Effect estimate: r=0.07
p-value: p=0.029
BACKGROUND AND PURPOSE: Insulin resistance and hyperinsulinemia have been associated with atherosclerosis. Recent attention has focused on the possible role of proinsulin because most radioimmunoassays for insulin cross-react with proinsulin. Therefore, it is not known which of the two, insulin per se or proinsulin, is more strongly related to atherosclerosis. METHODS: We examined the relation between fasting proinsulin, fasting split proinsulin, fasting and 2-hour insulin (after oral glucose load), and intima-media wall thickness (IMT) in the common carotid artery (CCA) and internal carotid artery (ICA) in 985 nondiabetic subjects from the Insulin Resistance Atherosclerosis Study, a multiethnic study of insulin resistance and atherosclerosis. RESULTS: In the overall population, a weak but significant relation between proinsulin and CCA IMT was observed (r=0.07, P=0.029). However, the relation between proinsulin and IMT was stronger in Hispanics and non-Hispanic whites than in African Americans. In non-Hispanic whites and Hispanics, significant correlations between CCA and proinsulin (r=0.087) and between ICA and proinsulin (r=0.101), split proinsulin (r = 0.092), and fasting insulin (r = 0.087) were observed. The significant correlations became more attenuated (and nonsignificant) after adjustment for cardiovascular risk factors, especially plasminogen activator inhibitor-1 (PAI-1). CONCLUSIONS: The association between proinsulin and IMT, while weak, appears to be stronger than the association between insulin and IMT. Adjustment for PAI-1 markedly attenuated the association between proinsulin and IMT, suggesting a possible mediating role for PAI-1 in this association. It is possible that proinsulin may represent a marker of atherosclerosis rather than a causal factor for atherosclerosis. Studies of the insulin resistance syndrome and atherosclerosis that use insulin as a surrogate for insulin resistance should consider the use of specific insulin assays as well as determination of proinsulin concentrations.
Haffner et al. (Sat,) conducted a observational in Atherosclerosis (n=985). Proinsulin and insulin concentrations was evaluated on Intima-media wall thickness (IMT) in the common carotid artery (CCA) and internal carotid artery (ICA) (r=0.07, p=0.029). Fasting proinsulin showed a weak but significant correlation with common carotid artery intima-media thickness (r=0.07, P=0.029), which was markedly attenuated after adjustment for PAI-1.