Journal
DIABETOLOGIA
Volume 65, Issue 1, Pages 88-100Publisher
SPRINGER
DOI: 10.1007/s00125-021-05573-6
Keywords
Autoantibody; Biomarker; HOMA2-B; Risk prediction; TrialNet Pathway to Prevention; Type 1 diabetes
Categories
Funding
- NIH [R21DK119800]
- JDRF [3-PDF-2019-752-A-N]
- JDRF Australia [1-SRA-2020-900]
- National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases
- National Institute of Allergy and Infectious Diseases
- Eunice Kennedy Shriver National Institute of Child Health and Human Development [U01 DK061010, U01 DK061034, U01 DK061042, U01 DK061058, U01 DK085453, U01 DK085461, U01 DK085465, U01 DK085466, U01 DK085476, U01 DK085499, U01 DK085504, U01 DK085509, U01 DK103180, U01 DK103153]
- JDRF
- [U01 DK103266]
- [U01 DK103282]
- [U01 DK106984]
- [U01 DK107013]
- [U01 DK107014]
- [UC4 DK106993]
- [UC4 DK11700901]
- [U01 DK 106693-02]
Ask authors/readers for more resources
The study suggests that HOMA2-B may be used as a single-time-point measurement to stratify the risk of developing type 1 diabetes in Aab+ individuals. Lower HOMA2-B values were associated with higher risk and faster progression to type 1 diabetes.
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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available