The 13C glucose breath test accurately identifies insulin resistance in people with type 1 diabetes

Abstract Objective This study investigated whether the delta-over-baseline of exhaled 13CO2 (Δ13CO2), generated from a 13C glucose breath test (13C-GBT), measured insulin resistance (IR) in people with type 1 diabetes, using the hyperinsulinemic-euglycemic clamp (HEC) as a reference method. The secondary objective was to compare the 13C-GBT with the estimated glucose disposal rate (eGDR). Methods A 40 mU/m2/min HEC and 2 separate 13C-GBTs (euglycemic with insulin bolus and hyperglycemic without bolus) were consecutively performed in 44 adults with type 1 diabetes with varying body compositions. eGDR was calculated based on hemoglobin A1c (HbA1c), presence of hypertension, and waist circumference. Results The mean glucose disposal rate (M-value) was 5.9 ± 3.1 mg/kg/min and mean euglycemic Δ13CO2 was 6.4 ± 2.1 δ‰, while median eGDR was 5.9 [4.3-9.8] mg/kg/min. The hyperglycemic Δ13CO2 did not correlate with the M-value, while the euglycemic Δ13CO2 and the M-value correlated strongly (r = 0.74, P < .001). The correlation between M-value and eGDR was more moderate (Spearman's rho = 0.63, P < .001). Linear regression showed an association between Δ13CO2 and M-value, adjusted for age, sex, and HbA1c ]adjusted R² = 0.52, B = 1.16, 95% confidence interval (CI) .80-1.52, P < .001]. The area under the receiver-operator characteristics curve for Δ13CO2 to identify subjects with IR (M-value < 4.9 mg/kg/min) was 0.81 (95% CI .68-.94, P < .001). The optimal cut-off for Δ13CO2 to identify subjects with IR was ≤ 5.8 δ‰. Conclusion Under euglycemic conditions, the 13C-GBT accurately identified individuals with type 1 diabetes and concurrent IR, suggesting its potential as a valuable noninvasive index. Clinical Trial Identifier: NCT04623320