Salivary extracellular RNA biomarkers for insulin resistance detection in hispanics. (October 2017)

• Record Type: Journal Article
• Authors: Zhang, Yong; Sun, Jie; Li, Feng; Grogan, Tristan R.; Vergara, Jose L.; Luan, QingXian; Park, Moon-Soo; Chia, David; Elashoff, David; Joshipura, Kaumudi J.; Wong, David T.W.
• Is Part Of: Diabetes research and clinical practice. Volume 132(2017)
• Page Start: 85
• Page End: 94
• Publication Date: 2017-10
• Subjects: Salivary biomarker -- Extracellular RNA -- Insulin resistance; Diabetes -- Periodicals; Diabetes Mellitus -- Periodicals; 616.462
• DOI: 10.1016/j.diabres.2017.07.008
• Languages: English
• ISSNs: 0168-8227

Abstract

Highlights: Saliva is a desirable non-invasive bodily fluid for biomarker detection in clinical applications. Performed the definitive validation of salivary biomarkers for insulin resistance detection. The first systematic disease, insulin resistance, for saliva biomarker development. Abstract: Aims: Insulin resistance (IR) detection is challenging and no test is currently used in clinical practice. We developed salivary biomarkers that could be used for IR detection. Methods: We collected saliva from 186 healthy and 276 pre-diabetic participants, divided them into high and low IR groups based on a HOMA cutoff of 2.5. We profiled extracellular transcriptome by microarray in saliva supernatant from 23 high IR and 15 low IR participants, and pre-validated the top ten extracellular mRNA (exRNA) markers in a new cohort of 40 high and 40 low IR participants. A prediction panel was then built and validated in an independent cohort of 149 high and 195 low IR participants. Results: Transcriptomic analyses identified 42 exRNA candidates differentially present in saliva of high and low IR participants. From the top ten candidates, six were individually validated (PRKCB, S100A12, IL1R2, CAMP, VPS4B, CAP1) (p < 0.01) and yielded AUC values ranging from 0.66 to 0.76. Body mass index (BMI) was significant higher in high compared to low IR group with AUC of 0.66, and showed no correlation with any of candidate biomarkers. The combination of four exRNA markers (IL1R2, VPS4B, CAP1, LUZP6) with BMI achieved excellent results in the prediction panel building dataset (AUC = 0.79, sensitivity = 79%, specificity = 64%). The prediction model was validated in an independent cohort (AUC = 0.82, sensitivity = 63%, specificity = 92%). Conclusions: A panel of four salivary exRNA biomarkers (IL1R2, VPS4B, CAP1, LUZP6) and BMI was validated that can distinguish high and low IR participants, overall and in subgroups of healthy and pre-diabetic participants.