Glycaemic variabilities: Key questions in pursuit of clarity.

After years of intensive investigation, the definition of glycaemic variability remains unclear and the term variability in glucose homoeostasis might be more appropriate covering both short and long-term glycaemic variability. For the latter, we remain in the search of an accurate definition and related targets. Recent work leads us to consider that the within-subject variability of HbA1c calculated from consecutive determinations of HbA1c at regular time-intervals could be the most relevant index for assessing the long-term variability with a threshold value of 5% (%CV = SD of HbA1c/mean HbA1c) to separate stability from lability of HbA1c. Presently, no one can deny that short- and long-term glucose variability should be maintained within their lower ranges to limit the incidence of hypoglycaemia. Usually, therapeutic strategies aimed at reducing post-meal glucose excursions, i.e. the major contributor to daily glucose fluctuations, exert a beneficial effect on the short-term glucose variability. This explains the effectiveness of adjunct therapies with either GLP- receptor agonists or SGLT inhibitors in type 2 diabetes. In type 1 diabetes, the application of a CGM device alone reduces the short-term glycaemic variability. In contrast, sophisticated insulin delivery does not necessarily lead to such reductions despite marked downward shifts of 24-hour glycaemic profiles. Such contrasting observations raise the question as to whether the prolonged wear of CGM devices is or not the major causative factor for improvement in glucose variability among intensively insulin-treated persons with type 1 diabetes.