Abstract
CONTEXT: Although glycated hemoglobin A1c is currently the best parameter used clinically to assess risk for the development of diabetes complications, it does not provide insight into short-term fluctuations in glucose levels. This review summarizes the relationship between continuous glucose monitoring (CGM)-derived metrics of glycemic variability and diabetes-related complications. EVIDENCE ACQUISITION: PubMed and Embase databases were searched from January 1, 2010 to August 22, 2020, using the terms type 1 diabetes, type 2 diabetes, diabetes-related microvascular and macrovascular complications, and measures of glycaemic variability. Exclusion criteria were studies that did not use CGM and studies involving participants who were not diabetic, acutely unwell (post stroke, post surgery), pregnant, or using insulin pumps. EVIDENCE SYNTHESIS: A total of 1636 records were identified, and 1602 were excluded, leaving 34 publications in the final review. Of the 20 852 total participants, 663 had type 1 diabetes (T1D) and 19 909 had type 2 diabetes (T2D). Glycemic variability and low time in range (TIR) showed associations with all studied microvascular and macrovascular complications of diabetes. Notably, higher TIR was associated with reduced risk of albuminuria, retinopathy, cardiovascular disease mortality, all-cause mortality, and abnormal carotid intima-media thickness. Peripheral neuropathy was predominantly associated with standard deviation of blood glucose levels (SD) and mean amplitude of glycemic excursions (MAGE). CONCLUSION: The evidence supports the association between diabetes complications and CGM-derived measures of intraday glycemic variability. TIR emerged as the most consistent measure, supporting its emerging role in clinical practice. More longitudinal studies and trials are required to confirm these associations, particularly for T1D, for which there are limited data.