Glycemic Variability: Risk Factors, Assessment, and Control.

Glycemic variability (GV) a well-established risk factor for hypoglycemia and a suspected risk factor for diabetes complications. GV is also a marker of the instability of a person's metabolic system, expressed as frequent high and low glucose excursions and overall volatile glycemic control. In this review, the author discusses topics related to the assessment, quantification, and optimal control of diabetes, including (1) the notion that optimal control of diabetes, that is, lowering of HbA1c-the commonly accepted gold-standard outcome-can be achieved only if accompanied by simultaneous reduction of GV; (2) assessment and visualization of the two principal dimensions of GV, amplitude and time, which is now possible via continuous glucose monitoring (CGM) and various metrics quantifying GV and the risks associated with hypo- and hyperglycemic excursions; and (3) the evolution of diabetes science and technology beyond quantifying GV and into the realm of GV control via pharmacological agents, for example, GLP-1 receptor agonists and DPP-4 inhibitors, which have pronounced variability-reducing effect, or real-time automated closed-loop systems commonly referred to as the "artificial pancreas." The author concludes that CGM allows close tracking over time, and therefore precise quantification, of glycemic variability in diabetes. The next step-optimal control of glucose fluctuations-is also taken by medications with pronounced GV-lowering effect primarily in type 2 diabetes, and by automated insulin delivery in type 1 diabetes. Contemporary CGM-based artificial pancreas systems use specific GV representations as input signals, and thus their main objective is to minimize GV and, from there, optimize glycemic control.