Aims/hypothesis <p>Efficient prediction of clinical type 1 diabetes is important for risk stratification and monitoring of autoantibody-positive individuals. In this study, we compared type 1 diabetes predictive models for predictive performance, cost and participant time needed for testing.</p> Methods <p>We developed 1943 predictive models using a Cox model based on a type 1 diabetes genetic risk score (GRS2), autoantibody count and types, BMI, age, self-reported gender and OGTT-derived glucose and C-peptide measures. We trained and validated the models using halves of a dataset comprising autoantibody-positive first-degree relatives of individuals with type 1 diabetes (<i>n</i>=3967, 49% female, 14.9 ± 12.1 years of age) from the TrialNet Pathway to Prevention study. The median duration of follow-up was 4.7 years (IQR 2.0–8.1), and 1311 participants developed clinical type 1 diabetes. Models were compared for predictive performances, estimated cost and participant time.</p> Results <p>Models that included metabolic measures had best performance, with most exhibiting small performance differences (less than 3% and <i>p</i>&gt;0.05). However, the cost and participant time associated with measuring metabolic variables ranged between US$56 and US$293 and 10–165 min, respectively. The predictive model performance had temporal variability, with the highest GRS2 influence and discriminative power being exhibited in the earliest preclinical stages. OGTT-derived metabolic measures had a similar performance to HbA<sub>1c</sub>- or Index<sub>60</sub>-derived models, with an important difference in cost and participant time.</p> Conclusions/interpretation <p>Cost–performance model analyses identified trade-offs between cost and performance models, and identified cost-minimising options to tailor risk-screening strategies.</p> Graphical Abstract <p></p>

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Type 1 diabetes prediction in autoantibody-positive individuals: performance, time and money matter

  • Lauric A. Ferrat,
  • Erin L. Templeman,
  • Andrea K. Steck,
  • Hemang M. Parikh,
  • Lu You,
  • Suna Onengut-Gumuscu,
  • Peter A. Gottlieb,
  • Taylor M. Triolo,
  • Stephen S. Rich,
  • Jeffrey Krischer,
  • R. Brett McQueen,
  • Richard A. Oram,
  • Maria J. Redondo

摘要

Aims/hypothesis

Efficient prediction of clinical type 1 diabetes is important for risk stratification and monitoring of autoantibody-positive individuals. In this study, we compared type 1 diabetes predictive models for predictive performance, cost and participant time needed for testing.

Methods

We developed 1943 predictive models using a Cox model based on a type 1 diabetes genetic risk score (GRS2), autoantibody count and types, BMI, age, self-reported gender and OGTT-derived glucose and C-peptide measures. We trained and validated the models using halves of a dataset comprising autoantibody-positive first-degree relatives of individuals with type 1 diabetes (n=3967, 49% female, 14.9 ± 12.1 years of age) from the TrialNet Pathway to Prevention study. The median duration of follow-up was 4.7 years (IQR 2.0–8.1), and 1311 participants developed clinical type 1 diabetes. Models were compared for predictive performances, estimated cost and participant time.

Results

Models that included metabolic measures had best performance, with most exhibiting small performance differences (less than 3% and p>0.05). However, the cost and participant time associated with measuring metabolic variables ranged between US$56 and US$293 and 10–165 min, respectively. The predictive model performance had temporal variability, with the highest GRS2 influence and discriminative power being exhibited in the earliest preclinical stages. OGTT-derived metabolic measures had a similar performance to HbA1c- or Index60-derived models, with an important difference in cost and participant time.

Conclusions/interpretation

Cost–performance model analyses identified trade-offs between cost and performance models, and identified cost-minimising options to tailor risk-screening strategies.

Graphical Abstract