CGM Metrics Identify Dysglycemic States in Participants From the TrialNet Pathway to Prevention Study

Abstract

Objective: Continuous glucose monitoring (CGM) parameters may identify individuals at risk for progression to overt type 1 diabetes. We aimed to determine whether CGM metrics provide additional insights into progression to clinical stage 3 type 1 diabetes.

Research design and methods: One hundred five relatives of individuals in type 1 diabetes probands (median age 16.8 years; 89% non-Hispanic White; 43.8% female) from the TrialNet Pathway to Prevention study underwent 7-day CGM assessments and oral glucose tolerance tests (OGTTs) at 6-month intervals. The baseline data are reported here. Three groups were evaluated: individuals with 1) stage 2 type 1 diabetes (n = 42) with two or more diabetes-related autoantibodies and abnormal OGTT; 2) stage 1 type 1 diabetes (n = 53) with two or more diabetes-related autoantibodies and normal OGTT; and 3) negative test for all diabetes-related autoantibodies and normal OGTT (n = 10).

Results: Multiple CGM metrics were associated with progression to stage 3 type 1 diabetes. Specifically, spending ≥5% time with glucose levels ≥140 mg/dL (P = 0.01), ≥8% time with glucose levels ≥140 mg/dL (P = 0.02), ≥5% time with glucose levels ≥160 mg/dL (P = 0.0001), and ≥8% time with glucose levels ≥160 mg/dL (P = 0.02) were all associated with progression to stage 3 disease. Stage 2 participants and those who progressed to stage 3 also exhibited higher mean daytime glucose values; spent more time with glucose values over 120, 140, and 160 mg/dL; and had greater variability.

Conclusions: CGM could aid in the identification of individuals, including those with a normal OGTT, who are likely to rapidly progress to stage 3 type 1 diabetes.

Graphical abstract

Figure 1

Dot plot violin charts for HbA_1c and various CGM metrics between low-risk, stage 1, and stage 2 participants. A: Mean overall glucose level; B: mean daytime (values between 6:00 a.m. and midnight) glucose level; C: time spent ≥120 mg/dL (%); D: time spent ≥140 mg/dL (%); E: time spent ≥160 mg/dL (%); F: HbA_1c (%); G: DySF (○, nonprogressors; ●, progressors).

Figure 2

Dot plot violin charts for HbA_1c and various CGM metrics between autoantibody-positive (AAb +) progressors and islet antibody-positive nonprogressors. A: Mean daytime (values between 6:00 a.m. and midnight) glucose level; B: HbA_1c (%); C: time spent ≥120 mg/dL (%); D: time spent ≥140 mg/dL (%); E: time spent ≥160 mg/dL (%); F: CONGA; G: DySF; H: MAGE; and I: MODD (○, nonprogressors; ●, progressors). Note that the results seen with DySF may appear opposite those of the other metrics, but this is due to its ability to measure volatility. While some outliers may be seen, the averages for all the patients are in line with the other metrics.

Figure 3

Progression to type 1 diabetes (T1D) by time spent ≥140 mg/dL and ≥160 mg/dL. A: Time spent ≥140 mg/dL with cutoff ≥5% vs. <5%; B: time spent ≥140 mg/dL with cutoff ≥8% vs. <8%; C: time spent ≥160 mg/dL with cutoff ≥5% vs. <5%; and D: time spent ≥160 mg/dL with cutoff ≥8% vs. <8%. Follow-up time was defined as the time between baseline CGM and diabetes onset for the progressors or last visit/contact for those who did not develop type 1 diabetes. CR, cumulative risk.