Toward Defining the Threshold Between Low and High Glucose Variability in Diabetes Diabetes Care 2017;40:832–838 | https://doi.org/10.2337/dc16-1769 OBJECTIVE To define the threshold for excess glucose variability (GV), one of the main fea- tures of dysglycemia in diabetes. RESEARCH DESIGN AND METHODS A total of 376 persons with diabetes investigated at the University Hospital of Mont- pellier (Montpellier, France) underwent continuous glucose monitoring. Participants with type 2 diabetes were divided into several groupsdgroups 1, 2a, 2b, and 3 (n = 82, 28, 65, and 79, respectively)daccording to treatment: 1) diet and/or insulin sensitizers alone; 2) oral therapy including an insulinotropic agent, dipeptidyl pepti- dase 4 inhibitors (group 2a) or sulfonylureas (group 2b); or 3) insulin. Group 4 included 122 persons with type 1 diabetes. Percentage coefficient of variation for glucose (%CV = [(SD of glucose)/(mean glucose)] 3 100) and frequencies of hypoglycemia (interstitial glucose <56 mg/dL [3.1 mmol/L]) were computed. RESULTS Percentages of CV (median [interquartile range]; %) increased significantly (P < 0.0001) from group 1 (18.1 [15.2–23.9]) to group 4 (37.2 [31.0–42.3]). In group 1, the upper limit of %CV, which served as reference for defining excess GV, was 36%. Percentages of patients with %CVs above this threshold in groups 2a, 2b, 3, and 4 were 0, 12.3, 19.0, and 55.7%, respectively. Hypoglycemia was more frequent in group 2b (P < 0.01) and groups 3 and 4 (P < 0.0001) when subjects with a %CV >36% were compared with those with %CV £36%. CONCLUSIONS A %CV of 36% appears to be a suitable threshold to distinguish between stable and unstable glycemia in diabetes because beyond this limit, the frequency of hypo- glycemia is significantly increased, especially in insulin-treated subjects. At present, there is incontrovertible evidence that chronic hyperglycemia is a key player in the pathogenesis of all related complications from diabetes, both in type 1 (1,2) and type 2 diabetes (3,4). However, glucose variability (GV) and hypoglycemia, the second and third components of the “glucose triumvirate” (5), may also be considered as risk factors for vascular complications in diabetes. Excess GV is usually associated with increased risk of hypoglycemic events, necessitating a global therapeutic approach aimed at avoiding hypoglycemic episodes while maintaining the HbA 1c levels within an individually defined target range according to patient-centered therapeutic strate- gies (6). HbA 1c -based strategies are limited by the fact that they do not integrate GV, and at present, the role of GV in the development and progression of cardiovascular 1 Institute of Clinical Research, University of Montpellier, Montpellier, France 2 Department of Endocrinology, Diabetes, and Nutrition, Montpellier University Hospital, Uni- versity of Montpellier, Montpellier, France 3 Department of Endocrinology, Piti ˆ e-Salp´ etri` ere Hospital, Paris, France 4 Department of Statistics and Epidemiology, UMR 5149, Montpellier University Hospital, Uni- versity of Montpellier, Montpellier, France 5 Diabetes Research Group, Swansea University, Swansea, Wales, U.K. Corresponding author: Louis Monnier, louis. monnier@inserm.fr. Received 16 August 2016 and accepted 5 De- cember 2016. © 2017 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More infor- mation is available at http://www.diabetesjournals .org/content/license. See accompanying articles, pp. 943 and 951. Louis Monnier, 1 Claude Colette, 1 Anne Wojtusciszyn, 2 Sylvie Dejager, 3 Eric Renard, 2 Nicolas Molinari, 4 and David R. Owens 5 832 Diabetes Care Volume 40, July 2017 CLIN CARE/EDUCATION/NUTRITION/PSYCHOSOCIAL