Letter: “Nocturnal Hypoglycemia: Characterization with Continuous Glucose Monitoring in a Real-World Setting”

Dear Editor,

We read with great interest the recent article by Mitter et al., which offered valuable insights into the characteristics of nocturnal hypoglycemia as measured by continuous glucose monitoring (CGM) in individuals with type 1 and type 2 diabetes. The study’s large dataset and emphasis on real-world evidence make it an essential contribution to the literature. ¹ However, we would like to draw attention to three methodological limitations not explicitly discussed, which may substantially influence the interpretation and generalizability of the results.

First, the dataset was derived from users of the mySugr® mobile application who consented to share their CGM data. Such users are likely to be younger, more technologically engaged, and highly motivated in their self-management, characteristics not representative of the broader diabetes population. For example, a survey found that individuals with diabetes who used self-management applications demonstrated significantly higher self-care behavior scores (including blood glucose monitoring, diet, and exercise) compared with nonusers, suggesting self-selection of more engaged participants. ² Moreover, a systematic review indicated that many participants in diabetes studies were recruited through health centers or clinics, potentially reflecting individuals with stronger health-seeking behaviors, limiting generalizability. ³ Consequently, the applicability of the authors’ findings to older adults, less technologically inclined individuals, or those who do not use smartphone-based CGM systems remains uncertain.

Second, the authors defined the nocturnal period uniformly as 00:00–05:59 h. However, a recent study comparing clock-based nocturnal windows (00:00–06:00) with sleep periods determined by Fitbit trackers found significantly higher rates of hypoglycemia when events were anchored to actual sleep times rather than fixed clock intervals. ⁴ This suggests that a rigid time window may underestimate hypoglycemia occurring during sleep. Such misclassification could be particularly relevant for individuals whose sleep extends beyond these fixed boundaries (e.g., those who retire before midnight or awaken after 06:00). Consequently, the reported peak in hypoglycemia between midnight and 2:00 a.m. may reflect artifacts of the window definition rather than an actual physiological pattern.

Third, the study did not appear to adjust for several clinically meaningful covariates, such as insulin regimen details (basal versus bolus; pump versus injections), body mass index, comorbidities, meal timing, physical activity, alcohol intake, and sleep duration or quality. Without accounting for these factors, observed associations (for instance, between nocturnal hypoglycemia and next-day glycemia) may be confounded. Indeed, a longitudinal study found that sleep onset time and late sleep timing (after midnight) were independently associated with greater glucose variability in adults without diabetes, underscoring the importance of sleep behavior in glucose regulation. ⁵

Authors’ Contributions

H.A.N.: Conceptualization, writing—original draft, and review and editing. J.M.S.: Conceptualization and writing—review and editing. F.H.K.: Supervision, validation, and writing—review and editing.