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Hyperproinsulinemia in obesity and in type 2 diabetes and its relation to cardiovascular disease

ABSTRACT Introduction: Disproportionately elevated fasting levels of proinsulin immunoreactive material (PIM)relative to insulin immunoreactivity (IRI) are a well-established abnormality in type 2 diabetes. Thesignificance of this abnormality has been investigated and discussed in several studies. Areas covered: The present review focuses on the role of proinsulin and its conversion intermediates inthe development of type 2 diabetes, obesity and insulin resistance, and the potential role as a marker ofcardiovascular risk, including the most important studies in this field. Expert commentary: The composition of plasma PIM is heterogeneous comprising des(31,32)-proinsulin,intact proinsulin and small amounts of des(64,65)-proinsulin. Disproportionate hyperproinsulinemiaseems to occur early in the development and before the diagnosis of type 2 diabetes, and seemsassociated to disease progression. Obesity and insulin resistance does not influence fasting PIM/IRI levels in type 2 diabetes. Fasting PIM/IRI levels in type 2 diabetes are closely associated with the degree of impairment in insulin secretory capacity. Different type 2 diabetes alleles have been described associated with elevated PIM/IRI levels. Recent data suggests that proinsulin and its conversion intermediates may have a role as markers of increased risk of cardiovascular disease in glucose intolerance and type 2 diabetes.