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Increased Intact Proinsulin in the Oral Glucose Challenge Sample is an Early Indicator for Future Type 2 Diabetes Development - Case Reports and Evidence from the Literature by Andreas Pfützner, Anastasios Manessis, Mina R. Hanna, Jack Lewin

Background: Increased intact proinsulin in plasma is a highly specific biomarker for a major disruption of insulin-processing in the pancreatic β-cells with associated insulin resistance. Increased intact proinsulin in morning fasting plasma indicates not only incipient diabetes, but also increased risk of macrovascular events in the patient - of ten times before an actual diagnosis of diabetes - due to the convergence of β-cell dysfunction, insulin resistance, and chronic systemic inflammation. This has raised the question as to whether a marked increase in intact proinsulin levels after oral glucose load in healthy subjects might be considered as indicative for β-cell dysfunction and prediabetes.
Methods: A previous study from 2011 examined, inter alia, intact proinsulin levels in blood samples from twenty healthy study participants at baseline and two hours after an oral glucose tolerance test (OGTT) with 75 g glucose. Seventeen of the participants showed normal glucose levels at baseline and at two hours compared to 4 participants with normal intact proinsulin levels at baseline but increased intact proinsulin levels at two hours.
Results: All four patients went on to develop type 2 diabetes in the following 5 years. None of the other subjects from the previous investigation developed type 2 diabetes.
Conclusions: As also confirmed by recent literature, intact proinsulin provides a powerful, easily measured biomarker for β-cell dysfunction and insulin resistance in type 2 diabetes, as well as risk of future cardiovascular events regardless of the stage of diabetes.

DOI: 10.7754/Clin.Lab.2019.191011