Continuous Glucose Monitoring Metrics and Risks of Severe Hypoglycemia and Diabetic Ketoacidosis in Type 1 Diabetes: A Pooled Analysis.

OBJECTIVE

To investigate the link between continuous glucose monitoring (CGM) metrics and risk of severe hypoglycemia and diabetic ketoacidosis (DKA) in individuals of type 1 diabetes.

RESEARCH DESIGN AND

METHODS

We pooled individual-level data from 10 studies of type 1 diabetes. From a 14-day baseline period, we derived CGM metrics (time in range [TIR] 70-180 mg/dL, time above range [TAR], time below range [TBR], sensor mean glucose, SD, and percent coefficient of variation [%CV]) and CGM-defined hypo- and hyperglycemic episodes. We used Cox regression to evaluate associations with severe hypoglycemia and diabetic ketoacidosis, with and without adjustment for HbA1c.

RESULTS

Among 1,550 participants, 65 severe hypoglycemia and 163 DKA events occurred over a median follow-up of 16 weeks. Higher TBR <70 and <54 mg/dL, SD, %CV, and CGM-defined hypoglycemic episodes were associated with greater risk of severe hypoglycemia independent of HbA1c (e.g., hazard ratio [HR] 1.52 [1.29-1.79] per 1-SD higher TBR <70). Lower TIR and higher mean glucose, SD, %CV, TAR, and hyperglycemic episodes were associated with higher DKA risk; these associations were attenuated after HbA1c adjustment, but TIR, sensor mean glucose, and SD remained statistically and clinically significant (e.g., HR 0.76, 95% CI 0.60-0.97 per 1-SD higher TIR).

CONCLUSIONS

CGM hypoglycemic and glycemic variability metrics were associated with severe hypoglycemia risk independent of HbA1c, whereas TIR, mean glucose, and SD provided information for DKA risk beyond HbA1c. This supports the complementary value of CGM and HbA1c in risk assessment for severe hypoglycemia and DKA.