The Prognostic Value of Time in Range in Type 2 Diabetes

Continuous glucose monitoring (CGM) is the recommended approach to the assessment of hypoglycemia and glycemic variability in thesettingof type1diabetes (1). The latest generation of CGM systems measure glucose every minute or every few minutes, with devices providing ;1,300 to up to ;20,000 measurements per person for a 14-day wear period. With this many measurements per person, the question arises of how to summarize the data in the most clinically useful manner and best communicate the results to patients. Time in range has emerged as a CGM metric with clinical utility in the management of type 1 diabetes (2,3). Time in range is a relatively simple CGM metric, defined as the percent of time spent with glucose values within a target range, usually 70–180mg/dL (3.9– 10 mmol/L), although the target can be individualized. Time in range is automatically calculated and included in CGM system reports, alongwith percentage of time spent in hypoand hyperglycemic glucose ranges (i.e., below or above target), average glucose, standard deviation, and coefficient of variation. As costs have come down and device accuracy has improved, the adoption of CGM has increased, with up to 20–30% of some U.S. patient populations with type 1 diabetes currently using the technology (4). In patients with type 2 diabetes, the benefits and role of CGM in clinical management are less clear than in patients with type 1 diabetes. American Diabetes Association guidelines state that CGM may have a role in selected patients with type 2 diabetes, primarily thosewho are takingmultiple daily injections of insulin (5). There is limited evidence regarding the clinical utility of CGM in type 2 diabetes, and few studies have linked CGM metrics to clinical outcomes in this population. The study by Lu et al. (6) in this issue of Diabetes Care was undertaken to evaluate the association between time in range and risks of all-cause and cardiovascular mortality. The investigators enrolled 6,225 adult inpatients with type 2 diabetes admitted to the Shanghai Jiao Tong University Affiliated Sixth People’s Hospital from January 2005 to December 2015. The enrolled patients wore a CGM sensor (CGMS Gold, Medtronic, Northridge, CA) for up to 72 h during their hospital stay. Time in range was calculated as the percentage of time spent in the glucose range 70–180 mg/dL [3.9– 10 mmol/L] during a 24-h period (calculated from up to 288 glucose readings). Demographic and other clinical data, including hemoglobin A1c (A1C), were collected from the study participants at the time of hospitalization. The CGM and other study data were linked to mortality records via personal identification numbers, and cause of death was identified using ICD-10 codes. At the time of the analysis, death datawere available through 31 December 2018 for a median follow-up time of 6.9 years. In this inpatient population (mean age 62 years, 55% male, mean A1C 8.9% [74.0 mmol/mol], mean duration of diabetes 9.7 years), Lu et al. found that those persons who had lower percent time in range (compared with those with time in range .85%) had higher risk of all-cause and cardiovascular mortality. The investigators also confirmed that A1C was associated with all-cause and cardiovascular mortality, documenting a J-shaped association, similar to that seen in prior observational studies (7). There are several important considerations in the interpretation of these study results. First, the generalizability of these findings is unclear. This study population consisted entirely of hospitalized patients, CGM measurements were collected over a 72-h period using anolder-generation device, andonly 24h ofdata for eachpatientwas analyzed. It is generally thought that at least 10 days are necessary to get a reasonable sense of “usual” glucose patterns (8). It is uncertain how the study results might translate to ambulatory diabetes patient populations using current CGM technology and a longer period of data collection. Second, 67% of the participants in the studyweredescribed as insulin users, but it was not clear whether the use of insulinwas prehospitalization, during the