HOMA2-B enhances assessment of type 1 diabetes risk among TrialNet Pathway to Prevention participants

Aims/hypothesis Methods to identify individuals at highest risk for type 1 diabetes are essential for the successful implementation of disease-modifying interventions. Simple metabolic measures are needed to help stratify autoantibody-positive (Aab+) individuals who are at risk of developing type 1 diabetes. HOMA2-B is a validated mathematical tool commonly used to estimate beta cell function in type 2 diabetes using fasting glucose and insulin. The utility of HOMA2-B in association with type 1 diabetes progression has not been tested. Methods Baseline HOMA2-B values from single-Aab+ ( n = 2652; mean age, 21.1 ± 14.0 years) and multiple-Aab+ ( n = 3794; mean age, 14.5 ± 11.2 years) individuals enrolled in the TrialNet Pathway to Prevention study were compared. Cox proportional hazard models were used to determine associations between HOMA2-B tertiles and time to progression to type 1 diabetes, with adjustments for age, sex, HLA status and BMI z score. Receiver operating characteristic (ROC) analysis was used to test the association of HOMA2-B with type 1 diabetes development in 1, 2, 5 and 10 years. Results At study entry, HOMA2-B values were higher in single- compared with multiple-Aab+ Pathway to Prevention participants (91.1 ± 44.5 vs 83.9 ± 38.9; p < 0.001). Single- and multiple-Aab+ individuals in the lowest HOMA2-B tertile had a higher risk and faster rate of progression to type 1 diabetes. For progression to type 1 diabetes within 1 year, area under the ROC curve (AUC-ROC) was 0.685, 0.666 and 0.680 for all Aab+, single-Aab+ and multiple-Aab+ individuals, respectively. When correlation between HOMA2-B and type 1 diabetes risk was assessed in combination with additional factors known to influence type 1 diabetes progression (insulin sensitivity, age and HLA status), AUC-ROC was highest for the single-Aab+ group’s risk of progression at 2 years (AUC-ROC 0.723 [95% CI 0.652, 0.794]). Conclusions/interpretation These data suggest that HOMA2-B may have utility as a single-time-point measurement to stratify risk of type 1 diabetes development in Aab+ individuals. Graphical abstract