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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.
Declaration of interest
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.