[¹¹C]5-hydroxy-tryptophan PET for Assessment of Islet Mass During Progression of Type 2 Diabetes

[¹¹C]5-hydroxy-tryptophan ([¹¹C]5-HTP) positron emission tomography of the pancreas has been shown to be a surrogate imaging biomarker of pancreatic islet mass. The change in islet mass in different stages of type 2 diabetes (T2D) as measured by noninvasive imaging is currently unknown. Here, we describe a cross-sectional study where subjects at different stages of T2D development with expected stratification of pancreatic islet mass were examined in relation to individuals without diabetes. The primary outcome was the [¹¹C]5-HTP uptake and retention in pancreas, as a surrogate marker for the endogenous islet mass. We found that metabolic testing indicated a progressive loss of β-cell function, but this was not mirrored by a decrease in [¹¹C]5-HTP tracer accumulation in the pancreas. This provides evidence of retained islet mass despite decreased β-cell function. The results herein indicate that β-cell dedifferentiation, and not necessarily endocrine cell loss, constitutes a major cause of β-cell failure in T2D.