Battelle Pacific Northwest Laboratories has received USD 1.92 million in first-year funding under a new NIH R01 grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to develop blood-based biomarkers of islet cell dysfunction across the natural history of type 1 diabetes (T1D), addressing a persistent gap in tools for monitoring disease progression and treatment response.
The project centers on intermediate products of prohormone processing — partially cleaved peptides generated as α-cells and β-cells convert precursor hormones into their active forms. Because altered prohormone processing has been observed at different stages of T1D, the researchers hypothesize that circulating intermediates could provide cell-type-specific measures of islet dysfunction and potentially predict disease progression. The research team, led by principal investigators Emily K. Sims and Wei-Jun Qian, will use advanced top-down and bottom-up proteomics on human islet tissue to identify candidate markers, then build a multiplexed liquid chromatography-mass spectrometry (LC-MS) assay using parallel reaction monitoring to quantify multiple prohormone products simultaneously in blood. Longitudinal samples from the Diabetes Prevention Trial (DPT-1) and other clinical cohorts will be used to examine how marker patterns shift across disease stages and evaluate their predictive value for T1D progression.
The clinical rationale is that C-peptide, a widely used measure of residual β-cell function in T1D trials, primarily reflects endogenous insulin secretion and provides limited insight into dysfunction across other islet cell populations. Multiplexed prohormone markers spanning α- and β-cell function could improve patient stratification and outcome monitoring in prevention and intervention studies.