Essential Continuous Glucose Monitoring Metrics: The Principal Dimensions of Glycemic Control in Diabetes.

Background: With the proliferation of continuous glucose monitoring (CGM), a number of metrics were developed to assess quality of glycemic control. Many of them are highly correlated. Thus, we aim to identify the principal dimensions of glycemic control-a minimal set of metrics, necessary and sufficient for comprehensive assessment of diabetes management. Methods: Seventy-five thousand five hundred sixty-three 2-week CGM profiles recorded in six studies by 790 individuals with type 1 or type 2 diabetes were used to compute mean glucose (MG), percentage time >180 mg/dL (TAR), >250 mg/dL (TAR2), <70 mg/dL (TBR), <54 mg/dL (TBR2), and coefficient of variation (CV). The true dimensionality of the glycemic-metric space was identified in a training set (53,380 profiles) and validated in an independent test set (22,183 profiles). Results: Correlation analysis identified two blocks of metrics-(MG, TAR, TAR2) and (TBR, TBR2, CV)-each with high internal correlation, but insignificant between-block correlation, suggesting that the true dimensionality of the glycemic-metric space is 2. Principal component analysis confirmed two essential metrics quantifying exposure to hyperglycemia (i.e., treatment efficacy) and risk for hypoglycemia (i.e., treatment safety), and explaining ∼90% of the variance in the training and test data. Conclusion: Two essential metrics, treatment efficacy and treatment safety, are necessary and sufficient to characterize glycemic control in diabetes. Thus, quantitatively, diabetes treatment optimization is reduced to a two-dimensional problem, meaning that minimizing both exposure to hyperglycemia and risk for hypoglycemia will lead to improvement in any other metric of glycemic control.