Glucose Variability of Individuals without Diabetes Using a Long-Term Continuous Glucose Monitoring System

Abstract

Background: Prior investigations regarding glucose variability in nondiabetic subjects measured by continuous glucose monitoring (CGM) have been limited to only few weeks. Little is known about what defines healthy or pathologic glycemic variability. This study investigated “normal glycemia” under daily conditions using a long-term implantable CGM system in nondiabetic adults for 90 days. Methods: 25 adult nondiabetic participants (10 Male, 15 Female, 17 participants >45 years old) were inserted with the Eversense® CGM System (Senseonics Inc, MD). Participants were instructed to continuously wear the CGM system during the 90 day period and calibrate the system when prompted. Analysis was performed to estimate standardized measures of euglycemia (70-180 mg/dL), hypoglycemia (<54, <70 mg/dL), hyperglycemia (>180, >200 mg/dL) and glucose variability (Mean, SD, CV). Results: Out of 25 participants, 5 had inadequate data for inclusion. Analysis showed the average glucose value of the nondiabetic participants was 102 mg/dL (SD=18 and CV=0.17). Average percent time spent in hypoglycemia <54mg/dL was 0.14% and <70mg/dL was 1.5%. Time spent in euglycemia 70-180 mg/dL was 98%. Time spent in hyperglycemia >180 and >200 mg/dL was 0.17% and 0.05%, respectively. 17 participants had at least one value < 54mg/dL and 18 participants had glucose values >180mg/dL with 11 subjects with glucose values > 200mg/dL. Conclusions: Glycemic variability recorded over extended period of time in participants without a diagnosis of diabetes showed similar results as observed by previous researchers over short duration with tight glycemic control. However, hypo- and hyperglycemic excursions are in some normoglycemic regarded individuals more frequent than suggested without CGM. Further analysis including meal challenge and fasting levels may provide guidance regarding expected values for persons without a diagnosis of diabetes and to set realistic target ranges for those with diabetes. Disclosure D. Deiss: Consultant; Self; Senseonics. Advisory Panel; Self; Abbott. Consultant; Self; Roche Diabetes Care Health and Digital Solutions. Advisory Panel; Self; Becton, Dickinson and Company. T. Abtahi: Other Relationship; Self; Senseonics. R. Rastogi: Employee; Self; Senseonics. E.L. Kelley: Employee; Self; Senseonics.

Evaluation of Reference Metrics for Continuous Glucose Monitoring in Persons Without Diabetes and Prediabetes

“…The difference may be explained by approximately 20% of individuals excluded due to prediabetes or diabetes detected with OGTT in the current study. Others have also evaluated glycemic metrics primarily in persons without glucose disturbances, [19][20][21][22][23][24][25][26] although current CGM metrics used in guidelines were generally not a focus of attention since these studies were performed before current guidelines were introduced. 5 Estimates for different metrics have generally differed, with SD 0.8-1.5 mmol/L (13.5-27 mg/dL) [20][21][22][23][24] and time-in-hypoglycemia <3.9 mmol/L between 1.5% and 1.7%.…”

“…Others have also evaluated glycemic metrics primarily in persons without glucose disturbances, [19][20][21][22][23][24][25][26] although current CGM metrics used in guidelines were generally not a focus of attention since these studies were performed before current guidelines were introduced. 5 Estimates for different metrics have generally differed, with SD 0.8-1.5 mmol/L (13.5-27 mg/dL) [20][21][22][23][24] and time-in-hypoglycemia <3.9 mmol/L between 1.5% and 1.7%. 20,23 Earlier studies also did not use masked CGM, [21][22][23][24][25][26] which may influence glucose levels to some extent.…”

“…5 Estimates for different metrics have generally differed, with SD 0.8-1.5 mmol/L (13.5-27 mg/dL) [20][21][22][23][24] and time-in-hypoglycemia <3.9 mmol/L between 1.5% and 1.7%. 20,23 Earlier studies also did not use masked CGM, [21][22][23][24][25][26] which may influence glucose levels to some extent. 11,13 Others used earlier generation CGM sensors, which were generally less accurate than the Dexcom G4.…”

“…19,21,[24][25][26] To date, no studies have evaluated the accuracy of CGM sensors in persons without diabetes or prediabetes. [19][20][21][22][23]25,26 It is of interest that we did not find a systematic deviation in accuracy, despite controlling for one, as this could influence estimated time in hypoglycemic range. People without diabetes or prediabetes have glucose levels close to the hypoglycemic range over extended periods of time where a systematic deviation could shift values registered in that range.…”

Innovative Solution or Cause for Concern? The Use of Continuous Glucose Monitors in People Not Living with Diabetes: A Narrative Review.

“…Existing research on CGMs in PNLD indicates 73% of normoglycemic participants exhibit PG that surpasses these thresholds aligning with prediabetic patterns [43]. This assertion gains credence with data illustrating that normoglycemic subjects often achieve glucose excursions paralleling IGT and diabetic levels [44], insinuating a potential onset of prediabetes [43]. However, it is crucial to note that these elevated glucose excursions might be normal physiological responses to increased carbohydrate or sugar consumption or other external stressors [45].…”