Novel Detection and Progression Markers for Diabetes Based on Continuous Glucose Monitoring Data Dynamics

Abstract

Context: Static measures of continuous glucose monitoring (CGM) data, such as time spent in specific glucose ranges (70-180 mg/dL or 70-140 mg/dL), do not fully capture the dynamic nature of blood glucose, particularly the subtle gradual deterioration of glycemic control over time in individuals with early-stage type 1 diabetes. Objective: Develop a diabetes diagnostic tool based on 2 markers of CGM dynamics: CGM entropy rate (ER) and Poincaré plot (PP) ellipse area (S). Methods: A total of 5754 daily CGM profiles from 843 individuals with type 1, type 2 diabetes, or healthy individuals with or without islet autoantibody status were used to compute 2 individual dynamic markers: ER (in bits per transition; BPT) of daily probability matrices describing CGM transitions between 8 glycemic states, and the area S (mg2/dL2) of individual CGM PP ellipses using standard PP descriptors. The Youden index was used to determine "optimal" cut-points for ER and S for health vs diabetes (case 1); type 1 vs type 2 (case 2); and low vs high type 1 immunological risk (case 3). The markers' discriminative power was assessed through the area under the receiver operating characteristics curves (AUC). Results: Optimal cutoff points were determined for ER and S for each of the 3 cases. ER and S discriminated case 1 with AUC = 0.98 (95% CI, 0.97-0.99) and AUC = 0.99 (95% CI, 0.99-1.00), respectively (cutoffs ERcase1 = 0.76 BPT, Scase1 = 1993.91 mg2/dL2), case 2 with AUC = 0.81 (95% CI, 0.77-0.84) and AUC = 0.76 (95% CI, 0.72-0.81), respectively (ERcase2 = 1.00 BPT, Scase2 = 5112.98 mg2/dL2), and case 3 with AUC = 0.72 (95% CI, 0.58-0.86), and AUC = 0.66 (95% CI, 0.47-0.86), respectively (ERcase3 = 0.52 BPT, Scase3 = 923.65 mg2/dL2). Conclusion: CGM dynamics markers can be an alternative to fasting plasma glucose or glucose tolerance testing to identify individuals at higher immunological risk of progressing to type 1 diabetes.