The following is a summary of “Whole Blood–based Transcriptional Risk Score for Nonobese Type 2 Diabetes Predicts Dynamic Changes in Glucose Metabolism,” published in the January 2024 issue of Endocrinology by Hou, et al.
The effectiveness of peripheral blood transcriptional markers in assessing the risk of type 2 diabetes (T2D) in individuals with a normal body mass index (BMI) remains uncertain. For a study, researchers sought to develop a whole blood–based transcriptional risk score (wb-TRS) for nonobese T2D and evaluate its impact on disease risk and changes in glucose metabolism dynamics.
A community-based cohort with blood transcriptome data was utilized to develop the wb-TRS, comprising 1,105 participants aged ≥40 who maintained a normal BMI for up to 10 years. The wb-TRS was subsequently validated in an external dataset. Additionally, potential biological implications were explored.
The wb-TRS consisted of 144 gene transcripts. Compared to the lowest tertile, participants in tertile 3 of the wb-TRS exhibited an 8.91-fold (95% CI, 3.53-22.5) higher risk of nonobese T2D, with each 1-unit increment associated with a 2.63-fold (95% CI, 1.87-3.68) higher risk. Moremenover, baseline wb-TRS significantly correlated with dynamic changes in average, daytime, nighttime, and 24-hour glucose levels, as well as HbA1c values and area under the curve of glucose measured by continuous glucose monitoring over a 6-month intervention period. The wb-TRS enhanced the predictive performance for nonobese T2D when combined with fasting glucose, triglycerides, and demographic and anthropometric parameters. Multi-contrast gene set enrichment (Mitch) analysis implicated oxidative phosphorylation, mTORC1 signaling, and cholesterol metabolism in the pathogenesis of nonobese T2D.
A whole blood–based transcriptional risk score for nonobese T2D was validated to predict dynamic changes in glucose metabolism. The results shed light on several biological pathways involved in developing nonobese T2D.