1138-P: Continuous Glucose Monitor (CGM)–Based Glycemic Variability Is Associated with Beta-Cell Function in Youth at Risk for Type 2 Diabetes

Introduction & Objective: Screening for type 2 diabetes (T2D) is recommended for youth with risk factors, but current tests do not assess β-cell function, a predictor of disease progression. We evaluated whether CGM-based glycemic variability (GV) is associated with β-cell function in youth at risk for T2D.

Methods: Prospective observational study of pubertal youth ages 8-18y not on glucose-altering medications, with overweight/obesity (BMI ≥ 85^th percentile) and at least one ADA-defined T2D risk factor or HbA1c 5.7-6.4%, fasting glucose (FG) ≥100 mg/dL, or 2-hour plasma glucose (2hG) on oral glucose tolerance test (OGTT) ≥140 mg/dL. Participants completed a 75g 2-hour OGTT, with every-30-minute glucose (G), insulin (I), and c-peptide (C). Blinded Dexcom G6 CGM was placed after OGTT and worn for 10 days. GV measures were calculated using the R package iglu, including coefficient of variation (CV), standard deviation (SD), mean amplitude of glycemic excursions (MAGE), and mean of daily difference (MODD). β-cell function was calculated using 2 versions of the OGTT-based oral disposition index (oDI): 1) I-oDI = 1/I_F x ΔI₃₀/ΔG₃₀ and 2) C-oDI = 1/C_F x ΔC₃₀/ΔG₃₀; Δ₃₀ is the difference from 0 to 30 minutes. Log-transformation was performed for skewed distributions. Linear regression was used to evaluate the association between oDI outcomes and GV measures, adjusted for BMI Z-score.

Results: Of 39 youth enrolled, 33 (55% F; 30% Black, 58% White, 12% multiracial; mean ± SD 14.9±1.8y; BMI 36.8±6.6 kg/m²; HbA1c 5.6±3.2%; FG 84.8±8.2 mg/dL; 2hG 116.2±28.9 mg/dL) had evaluable CGM data. MAGE and MODD were inversely associated with I-oDI (p=0.04, p=0.02) and C-oDI (p=0.009, p=0.016). CV (p=0.047) and SD (p=0.03) were inversely associated with C-oDI but not associated with I-oDI.

Conclusion: Based on its demonstrated association with β-cell function, CGM-based GV offers a novel approach to evaluating T2D risk in youth with overweight/obesity and other risk factors.