CircHIPK3, and has_circ_0071106 as biomarkers for diabetes among first degree relatives of type 2 diabetes patients

Background: Most patients in Egypt with prediabetes and 43% of those with diabetes are probably undiagnosed. So early detection of T2D is of utmost importance to prevent progression to irreversible complications. Many of the biomarkers used today for detection of diabetes are based on proteins. The discovery of circular RNA as a sensitive, and non-invasive biomarker opened new frontiers for diagnosis, prognosis, and therapeutic response prediction of diseases including diabetes. The aim of this study was to evaluate the potential of CircHIPK3 and hsa_circ_0071106 as diagnostic biomarkers for prediabetes in apparently healthy first-degree relatives of patients with T2D. Methods: This study is of case-control design. It includes 78 subjects distributed equally between cases and control groups. Glycemic profile parameters including (fasting and 2 hrs plasma glucose during oral glucose tolerance test, HbA1c, and insulin) in addition to calculation of Insulin resistance's homeostasis model assessment parameter (HOMA-IR) were performed. Expression level of CircHIPK3, and hsa_circ_0071106 was quantified using Quantitative real-time polymerase chain reaction (RT-qPCR). Results: In the relative’s group, subjects who had diabetes showed significantly higher levels of both CircHIPK3 and hsa_circ_0071106 in comparison to others that are either euglycemic or prediabetic (P<0.001, and P=0.003, respectively). The accuracy of the differentiation between T2DM patients and control subjects was comparable for CircHIPK3 and hsa_circ_0071106 (93.3%, and 96.7% respectively). Conclusions: Elevated levels of CircHIPK3 and hsa_circ_0071106 were significantly associated with the presence and progression of glucose impairment in 1st degree relatives of T2D. Specifically, CircHIPK3 seems to be an independent predictor of prediabetes.